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Diez-Martin E, Hernandez-Suarez L, Muñoz-Villafranca C, Martin-Souto L, Astigarraga E, Ramirez-Garcia A, Barreda-Gómez G. Inflammatory Bowel Disease: A Comprehensive Analysis of Molecular Bases, Predictive Biomarkers, Diagnostic Methods, and Therapeutic Options. Int J Mol Sci 2024; 25:7062. [PMID: 39000169 PMCID: PMC11241012 DOI: 10.3390/ijms25137062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 06/15/2024] [Accepted: 06/25/2024] [Indexed: 07/16/2024] Open
Abstract
In inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), the immune system relentlessly attacks intestinal cells, causing recurrent tissue damage over the lifetime of patients. The etiology of IBD is complex and multifactorial, involving environmental, microbiota, genetic, and immunological factors that alter the molecular basis of the organism. Among these, the microbiota and immune cells play pivotal roles; the microbiota generates antigens recognized by immune cells and antibodies, while autoantibodies target and attack the intestinal membrane, exacerbating inflammation and tissue damage. Given the altered molecular framework, the analysis of multiple molecular biomarkers in patients proves exceedingly valuable for diagnosing and prognosing IBD, including markers like C reactive protein and fecal calprotectin. Upon detection and classification of patients, specific treatments are administered, ranging from conventional drugs to new biological therapies, such as antibodies to neutralize inflammatory molecules like tumor necrosis factor (TNF) and integrin. This review delves into the molecular basis and targets, biomarkers, treatment options, monitoring techniques, and, ultimately, current challenges in IBD management.
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Affiliation(s)
- Eguzkiñe Diez-Martin
- Research and Development Department, IMG Pharma Biotech S.L., 48170 Zamudio, Spain
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
| | - Leidi Hernandez-Suarez
- Research and Development Department, IMG Pharma Biotech S.L., 48170 Zamudio, Spain
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
| | - Carmen Muñoz-Villafranca
- Department of Gastroenterology, University Hospital of Basurto, Avda Montevideo 18, 48013 Bilbao, Spain
| | - Leire Martin-Souto
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
| | - Egoitz Astigarraga
- Research and Development Department, IMG Pharma Biotech S.L., 48170 Zamudio, Spain
| | - Andoni Ramirez-Garcia
- Department of Immunology, Microbiology and Parasitology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain
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Vălean D, Zaharie R, Țaulean R, Usatiuc L, Zaharie F. Recent Trends in Non-Invasive Methods of Diagnosis and Evaluation of Inflammatory Bowel Disease: A Short Review. Int J Mol Sci 2024; 25:2077. [PMID: 38396754 PMCID: PMC10889152 DOI: 10.3390/ijms25042077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Revised: 02/04/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Inflammatory bowel diseases are a conglomerate of disorders causing inflammation of the gastrointestinal tract, which have gained a significant increase in prevalence in the 21st century. As they present a challenge in the terms of diagnosis as well as treatment, IBDs can present an overwhelming impact on the individual and can take a toll on healthcare costs. Thus, a quick and precise diagnosis is required in order to prevent the high number of complications that can arise from a late diagnosis as well as a misdiagnosis. Although endoscopy remains the primary method of evaluation for IBD, recent trends have highlighted various non-invasive methods of diagnosis as well as reevaluating previous ones. This review focused on the current non-invasive methods in the diagnosis of IBD, exploring their possible implementation in the near future, with the goal of achieving earlier, feasible, and cheap methods of diagnosis as well as prognosis in IBD.
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Affiliation(s)
- Dan Vălean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roxana Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of Gastroenterology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Roman Țaulean
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
| | - Lia Usatiuc
- Department of Patophysiology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania;
| | - Florin Zaharie
- Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, 400162 Cluj-Napoca, Romania; (D.V.); (R.Ț.); (F.Z.)
- Department of General Surgery, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400347 Cluj-Napoca, Romania
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Shao Y, Li L, Yang Y, Ye Y, Guo Z, Liu L, Huang J, Chen Y, Gao X, Sun B. DNase aggravates intestinal microvascular injury in IBD patients by releasing NET-related proteins. FASEB J 2024; 38:e23395. [PMID: 38149880 DOI: 10.1096/fj.202301780r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 12/02/2023] [Accepted: 12/15/2023] [Indexed: 12/28/2023]
Abstract
Neutrophils accumulate in the inflammatory mucosa of patients with inflammatory bowel disease (IBD), and excessive release of NETs (neutrophil extracellular traps may be one of the important factors that cause IBD progression. However, the specific mechanism underlying vascular injury caused by NETs remains unclear. Immunofluorescence, ELISA, and flow cytometry were used in this study to detect the expression of NETs and DNase in the tissue and peripheral blood samples of patients with IBD. DSS mouse model was used to detect colon injury and vascular permeability. We found that NETs and DNase levels increased in the colon of patients with IBD. We found an increase in the activity of NET-related MPO released by DNase. DNase released NET-related proteins and damaged vascular endothelial cells in vitro. In DSS mouse model, the synchronous increase of DNase and NETs in the colon leads to an increase in vascular injury markers (CD44, sTM). DNase aggravated colon injury and increased vascular permeability in vivo, which was inhibited by gentamicin sulfate (GS). GS does not reduce the expression of DNase, but rather reduces the release of NET-related proteins to protect vascular endothelium by inhibiting DNase activity. MPO and histones synergistically damaged the vascular endothelium, and vascular injury can be improved by their active inhibitors. We further found that H2 O2 is an important substrate for MPO induced vascular damage. In conclusion, in IBD, DNase, and NET levels increased synchronously in the lesion area and released NET-related proteins to damage the vascular endothelium. Therefore, targeting DNase may be beneficial for the treatment of IBD.
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Affiliation(s)
- Yiming Shao
- Department of Burns and Plastic Surgery, Affiliated Hospital of Jining Medical University, Jining, China
- Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Linbin Li
- Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Yunxi Yang
- Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Yulan Ye
- Department of Gastroenterology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Zaiwen Guo
- Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Lu Liu
- Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Jiamin Huang
- Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Yi Chen
- Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Xi Gao
- Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Bingwei Sun
- Research Center for Neutrophil Engineering Technology, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
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Maden M, Gülersoy E. Serum/Faecal S100A12, CRP and lactoferrin can be used to distinguish ınfectious and non-ınfectious canine diarrhoea. Vet Med Sci 2023; 9:2485-2496. [PMID: 37688789 PMCID: PMC10650241 DOI: 10.1002/vms3.1245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 07/17/2023] [Accepted: 08/18/2023] [Indexed: 09/11/2023] Open
Abstract
OBJECTIVES This study aimed to evaluate the diagnostic efficacies of selected inflammatory and intestinal biomarkers in cases of infectious and non-infectious diarrhoea in dogs. METHODS A total of 60 dogs, 12 healthy (Control Group) and 48 with diarrhoea were used. Viral, Bacterial, Parasitic (infectious) and Nutritional diarrhoea (non-infectious) subgroups (n: 12) were formed according to the aetiology, on the basis of clinical and laboratory examinations. Selected inflammatory and intestinal biomarkers (Calgranulin, S100A12; Lactoferrin, LCTF; C-reactive protein, CRP) were measured both in serum and faecal samples. RESULTS Compared to the Control and Nutritional Diarrhoea groups, the infectious diarrhoea groups had higher serum S100A12, LCTF, CRP, blood urea nitrogen, creatinine (CR), alanine transaminase and alkaline phosphatase, and lower glucose (GLU), sodium (Na) and potassium (K) concentrations (p < 0.05); Viral and Parasitic Diarrhoea groups had lower serum albumin (ALB) and total protein (TP) concentrations (p < 0.05). Faecal S100A12, LCTF and CRP concentrations were higher in infectious diarrhoea groups compared to the Control and Nutritional Diarrhoea groups (p < 0.05). Faecal LCTF and CRP concentrations were higher in the Bacterial Diarrhoea group than in the Viral and Parasitic Diarrhoea groups (p < 0.05). CLINICAL SIGNIFICANCE It was determined that serum (area under curve, AUC: 0.842 and 0.956) and faecal (AUC: 0.975 and 0.786) S100A12 and CRP concentrations in viral diarrhoea; serum (AUC: 0.956) and faecal (AUC: 0.992) LCTF concentrations in bacterial diarrhoea have diagnostic values in the diagnosis of the presence of intestinal inflammation and damage and can be used in the differential diagnosis of infectious and non-infectious diarrhoea.
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Affiliation(s)
- Mehmet Maden
- Department of Internal MedicineVeterinary FacultySelcuk UniversityKonyaTurkey
| | - Erdem Gülersoy
- Department of Internal MedicineVeterinary FacultyHarran UniversityŞanlıurfaTurkey
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Kałużna A, Jura-Półtorak A, Derkacz A, Olczyk K, Komosinska-Vassev K. Usefulness of Proguanylin, Pentraxin 3 and S100A12 Serum Concentrations in Diagnosis and Monitoring the Disease Activity in Crohn's Disease. Biomolecules 2023; 13:1448. [PMID: 37892129 PMCID: PMC10604875 DOI: 10.3390/biom13101448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 09/21/2023] [Accepted: 09/23/2023] [Indexed: 10/29/2023] Open
Abstract
The aim of our case-control study was to identify novel biomarkers of Crohn's disease (CD) that hold the potential to be employed in both disease diagnosis and monitoring activity. In the context of the contribution of intestinal barrier integrity and immune response to the pathogenesis of CD, we assessed the serum concentrations of proguanylin (pro-GN), pentraxin 3 (PTX3) and S100A12 in 20 patients before and after anti-inflammatory treatment, as well as in 20 healthy individuals. Statistical analyses revealed a significant difference in the levels of pro-GN (5.5 vs. 11.35, p < 0.001), PTX3 (2117.9 vs. 1608.37, p < 0.05) and S100A12 (79.4 vs. 19.74, p < 0.001) between pretreatment patients with CD and healthy individuals. Moreover, we noted a significant relationship between the serum profile of PTX3 and disease activity, expressed as CDAI, both before (p < 0.005, r = 0.63) and after (p < 0.05, r = 0.60) treatment. A similar correlation was noted in the case of S100A12 (p < 0.005, r = 0.81), albeit exclusively within the post-treatment group of patients. Anti-inflammatory treatment resulted in an elevation of pro-GN concentration (5.5 vs. 8.04, p < 0.001) and a reduction in PTX3 level (2117.9 vs. 1609.5, p < 0.05) in the serum of patients with CD. In comparison to our previous research conducted on a group of patients with ulcerative colitis (UC), those with CD exhibited reduced levels of PTX3 (2117.9 vs. 3197.05, p < 0.005) and elevated concentrations of S100A12 (79.4 vs. 39.36, p < 0.05). The results obtained from this investigation suggest that measurements of pro-GN, PTX3 and S100A12 could prove beneficial in the diagnosis of Crohn's disease. Assessment of changes in the serum profile of PTX3 appears to be a good marker of response to treatment but also, along with analysis of S100A12 protein serum levels, a useful marker in differentiating CD from UC.
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Affiliation(s)
- Aleksandra Kałużna
- Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland; (A.J.-P.); (K.O.); (K.K.-V.)
| | - Agnieszka Jura-Półtorak
- Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland; (A.J.-P.); (K.O.); (K.K.-V.)
| | | | - Krystyna Olczyk
- Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland; (A.J.-P.); (K.O.); (K.K.-V.)
| | - Katarzyna Komosinska-Vassev
- Department of Clinical Chemistry and Laboratory Diagnostics, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland; (A.J.-P.); (K.O.); (K.K.-V.)
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Witarto BS, Visuddho V, Witarto AP, Sampurna MTA, Irzaldy A. Performance of fecal S100A12 as a novel non-invasive diagnostic biomarker for pediatric inflammatory bowel disease: a systematic review and meta-analysis. J Pediatr (Rio J) 2023; 99:432-442. [PMID: 37094752 PMCID: PMC10492162 DOI: 10.1016/j.jped.2023.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 03/18/2023] [Accepted: 03/20/2023] [Indexed: 04/26/2023] Open
Abstract
OBJECTIVE The incidence and prevalence of inflammatory bowel disease (IBD) in pediatric patients are increasing. Currently, the diagnostic method for IBD is inconvenient, expensive, and difficult. S100A12, a type of calcium-binding protein, detected in the feces of patients with IBD has recently been suggested as a promising diagnostic tool. Hence, the authors aimed to evaluate the accuracy of fecal S100A12 in diagnosing IBD in pediatric patients by performing a meta-analysis. METHODS The authors performed a systematic literature search in five electronic databases for eligible studies up to July 15, 2021. Pooled diagnostic accuracies of fecal S100A12 were analyzed as the primary outcomes. Secondary outcomes were standardized mean difference (SMD) of fecal S100A12 levels between IBD and non-IBD groups and a comparison of diagnostic accuracies between fecal S100A12 and fecal calprotectin. RESULTS Seven studies comprising 712 children and adolescents (474 non-IBD controls and 238 IBD cases) were included. Fecal S100A12 levels were higher in the IBD group than in the non-IBD group (SMD = 1.88; 95% confidence interval [CI] = 1.19-2.58; p < 0.0001). Fecal S100A12 could diagnose IBD in pediatric patients with a pooled sensitivity of 95% (95% CI = 88%-98%), specificity of 97% (95% CI = 95%-98%), and area under the receiver operating summary characteristics (AUSROC) curve of 0.99 (95% CI = 0.97-0.99). Fecal S100A12 specificity and AUSROC curve values were higher than those of fecal calprotectin (p < 0.05). CONCLUSION Fecal S100A12 may serve as an accurate and non-invasive tool for diagnosing pediatric IBD.
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Affiliation(s)
| | - Visuddho Visuddho
- Universitas Airlangga, Faculty of Medicine, Medical Program, Surabaya, Indonesia
| | | | - Mahendra Tri Arif Sampurna
- Universitas Airlangga, Airlangga Teaching Hospital, Faculty of Medicine, Department of Pediatrics, Surabaya, Indonesia; Universitas Airlangga, Dr. Soetomo General Hospital, Faculty of Medicine, Department of Pediatrics, Surabaya, Indonesia.
| | - Abyan Irzaldy
- University Medical Center Rotterdam, Department of Public Health, Erasmus MC, Rotterdam, the Netherlands
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Magalhaes D, Peyrin-Biroulet L, Estevinho MM, Danese S, Magro F. Pursuing neutrophils: systematic scoping review on blood-based biomarkers as predictors of treatment outcomes in inflammatory bowel disease. Therap Adv Gastroenterol 2023; 16:17562848231155987. [PMID: 36923488 PMCID: PMC10009059 DOI: 10.1177/17562848231155987] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 01/23/2023] [Indexed: 03/14/2023] Open
Abstract
Background Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need. Neutrophil-related biomarkers have been mainly studied in the feces, but blood analyses have inherent advantages. Objective To review the recent learnings on the ability of blood-based neutrophil-expressed biomarkers to predict treatment outcomes in IBD. Design Systematic scoping review. Data sources and methods We performed a literature search in Pubmed, EMBASE, SCOPUS, Web of Science, ScienceDirect, and Cochrane Central Register of Controlled Trials from inception until May 2022 according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. All human studies associating blood-based neutrophil-related compounds with the prediction of disease progression, complication onset, or treatment outcomes were included. Results From 1032 retrieved entries, 34 studies were selected, 32 published in 2013 or later. In all, 17 biomarkers from granules, cytoplasm, plasmatic membrane, and plasma were explored. In total, 1850 Crohn's disease (CD) and 1122 ulcerative colitis non-duplicated patients were included. The most mentioned biomarkers were nCD64, serum calprotectin (SC), oncostatin M (OSM), neutrophil elastase-generated calprotectin fragment (CPa9-HNE), and triggering receptor expressed on myeloid cells 1 (TREM1). Six biomarkers showed promising results: OSM, SC, eNAMPT, nCD64, TREM1, and CPa9-HNE. Variable positive signals were found for human neutrophil peptide 1-3, LL-37, S100A12, and neutrophil gelatinase-associated lipocalin. No predictive ability was found for the remaining markers. Sharing a neutrophil compartment did not indicate similar behavior. Conclusion Advances in the last decade began to unveil the untapped potential of the readily accessible blood neutrophil-expressed biomarkers, especially nCD64, TREM1, and CPa9-HNE. Current evidence suggests that future research should focus on well-defined subpopulations instead of a one-size-fits-all biomarker. Registration https://osf.io/kes9a.
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Affiliation(s)
- Diogo Magalhaes
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and Inserm NGERE U1256, University Hospital of Nancy, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | - Maria Manuela Estevinho
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal
- Department of Gastroenterology, Vila Nova de Gaia/Espinho Hospital Center, Vila Nova de Gaia, Portugal
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- IBD center, Humanitas Research Hospital, IRCCS, Rozzano, Milan, Italy
| | - Fernando Magro
- Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Rua Dr. Plácido Costa, 3, Porto, 4200-450, Portugal
- Department of Gastroenterology, São João Hospital University Centre, Porto, Portugal
- Center for Health Technology and Services Research (CINTESIS), Porto, Portugal
- Unidade de Farmacologia Clínica, São João Hospital University Centre, Porto, Portugal
- Portuguese Inflammatory Bowel Disease group (GEDII)
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Li M, Tao Y, Sun Y, Wu J, Zhang F, Wen Y, Gong M, Yan J, Liang H, Bai X, Niu J, Miao Y. Constructing a prediction model of inflammatory bowel disease recurrence based on factors affecting the quality of life. Front Med (Lausanne) 2023; 10:1041505. [PMID: 36968835 PMCID: PMC10034041 DOI: 10.3389/fmed.2023.1041505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 02/15/2023] [Indexed: 03/11/2023] Open
Abstract
AimThis study aimed to determine the factors affecting the quality of life of patients with inflammatory bowel disease (IBD) and to construct a disease recurrence prediction model based on these influencing factors.MethodsA prospective, single-center study in China was conducted between October 2020 and March 2021. The quality of life of patients was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). Multiple stepwise regression analysis was used to analyze the factors influencing the quality of life of patients with IBD. The chi-square test and the point-biserial correlation analysis were performed to identify factors associated with clinical recurrence. A binary logistic regression model was constructed to predict the recurrence. The receiver operating characteristic curve was used to evaluate the prediction model. Patients with IBD from April 2021 to June 2021 were randomly included for model verification to evaluate the disease recurrence prediction model.ResultsThe average IBDQ score of patients with IBD was 172.2 ± 35.0 (decreased by 23.2%). The scores of all dimensions of the IBDQ were decreased, especially emotional function and systemic symptoms. Disease activity, age, extraintestinal manifestations (EIMs), and annual household income were important factors influencing the IBDQ scores of patients with ulcerative colitis, and these accounted for ~57.0% of the factors affecting the quality of life. Disease activity, EIMs, and occupational stress were important factors influencing the IBDQ scores of patients with Crohn's disease, and they accounted for approximately 75.1% of the factors affecting the quality of life. Annual household income, occupational stress, and IBDQ scores were independent risk factors for recurrence. The area under the curve of the recurrence prediction model was 81.1%. The sensitivity and specificity were 81.7 and 71.7%, respectively. The Youden index of the model was 0.534. The established recurrence prediction model has good discriminant validity in the validation cohort.ConclusionThe quality of life of patients with IBD was generally poor. The use of factors affecting the quality of life to predict disease recurrence has high predictive value and can support the management of IBD by selecting patients at a higher risk for relapse.
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Affiliation(s)
- Maojuan Li
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Yan Tao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Yang Sun
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Jing Wu
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Fengrui Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Yunling Wen
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Min Gong
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Jingxian Yan
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Hao Liang
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Xinyu Bai
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Junkun Niu
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
- Junkun Niu
| | - Yinglei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
- Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
- *Correspondence: Yinglei Miao
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Zornow KA, Slovak JE, Lidbury JA, Suchodolski JS, Steiner JM. Fecal S100A12 concentrations in cats with chronic enteropathies. J Feline Med Surg 2023; 25:1098612X231164273. [PMID: 36995216 PMCID: PMC10812014 DOI: 10.1177/1098612x231164273] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/31/2023]
Abstract
OBJECTIVES The aim of this study was to compare fecal S100A12 concentrations in cats diagnosed with chronic enteropathy (CE) with healthy control cats. METHODS This was a prospective, cross-sectional study. Forty-nine cats that had gastrointestinal signs for >3 weeks and a complete diagnostic work-up, including bloodwork, abdominal ultrasound and upper and/or lower gastrointestinal endoscopic biopsies, were enrolled into the CE group. Nineteen cats from the CE group were diagnosed with inflammatory bowel disease (IBD) or chronic inflammatory enteropathy (CIE) and 30 with alimentary lymphoma (LSA), based on histopathology results and additional testing with immunohistochemistry or molecular clonality testing with PCR if indicated. Nineteen apparently healthy control cats were included in the study. One fecal sample was collected from each cat and S100A12 concentrations were quantified by an analytically validated in-house ELISA. RESULTS Fecal S100A12 concentrations differed between cats with LSA (median 110 ng/g; interquartile range [IQR] 18-548) and control cats (median 4 ng/g; IQR 2-25 [P <0.001]) and between cats with IBD (median 34 ng/g; IQR 15-973) and control cats (P <0.003). S100A12 concentrations in CE cats (median 94 ng/g; IQR 16-548) were statistically significantly higher compared with control cats (P <0.001). The area under the receiver operating characteristic curve (AUROC) to separate healthy cats from CE cats was 0.81 (95% confidence interval [CI] 0.70-0.92) and was statistically significant (P <0.001). The AUROC to separate cats with IBD from cats with LSA was 0.51 (95% CI 0.34-0.68) and was not statistically significant (P = 0.9). CONCLUSIONS AND RELEVANCE Fecal S100A12 concentrations at the time of diagnostic investigation were higher in cats with CIE and LSA than in healthy controls but did not differ between cats with LSA and those with CIE/IBD. This study is an initial step toward evaluating a novel non-invasive marker of feline CIE. Further studies are needed to determine the diagnostic utility of fecal S100A12 concentrations in cats with CE, including comparing cats with IBD/CIE and LSA, and to compare them with cats with extra-gastrointestinal disease.
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Affiliation(s)
- Kailee A Zornow
- Internal Medicine Department, Schwarzman Animal Medical Center, New York, NY, USA
| | - Jennifer E Slovak
- Internal Medicine Department, Schwarzman Animal Medical Center, New York, NY, USA
| | - Jonathan A Lidbury
- Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
| | - Joerg M Steiner
- Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
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Volkers AG, Appleton L, Gearry RB, Frampton CM, de Voogd FAE, Peters van Ton AM, Leach ST, Lemberg DA, Day AS. Fecal Calprotectin, Chitinase 3-Like-1, S100A12 and Osteoprotegerin as Markers of Disease Activity in Children with Crohn’s Disease. GASTROINTESTINAL DISORDERS 2022; 4:180-189. [DOI: 10.3390/gidisord4030017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/10/2023] Open
Abstract
Fecal calprotectin (FC), chitinase 3-like-1 protein (CHI3L1), S100A12 and osteoprotegerin (OPG) are biomarkers of intestinal inflammation. This cross-sectional study aimed to evaluate these biomarkers in a cohort of children with Crohn’s disease (CD) and compare them with other measures of disease activity. Stool samples from children with CD were used to measure FC, CHI3L1, S100A12 and OPG by enzyme-linked immunosorbent assay. Serum inflammatory markers were measured and pediatric CD disease activity index (PCDAI) scores calculated. The simple endoscopic score for CD (SES-CD) was reported for a subgroup who underwent ileocolonoscopy corresponding with the stool samples. Sixty-five children were recruited. Children in clinical remission had lower FC and CHI3L1 levels than those with active disease (FC: 277 vs. 1648 µg/g, p = 0.012; CHI3L1: 23 vs. 227 ng/g, p = 0.013). FC levels differed between patients with clinically active or inactive isolated ileal CD. Although FC and CHI3L1 levels correlated strongly (r = 0.83), none of the fecal markers correlated well with serum markers. Only FC and OPG correlated with SES-CD scores (r = 0.57 and r = 0.48, respectively). In conclusion, FC correlated with both endoscopic and clinical disease activity and was the only biomarker that differentiated between active and inactive ileal CD. CHI3L1 also predicted clinical disease activity and correlated highly with FC. Further investigation of the role of CHI3L1 is required.
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Affiliation(s)
- Adriaan G. Volkers
- Department of Paediatrics, University of Otago Christchurch, Christchurch 8011, New Zealand
- Department of Gastroenterology and Hepatology, Amsterdam UMC, 1105 Amsterdam, The Netherlands
| | - Laura Appleton
- Department of Paediatrics, University of Otago Christchurch, Christchurch 8011, New Zealand
| | - Richard B. Gearry
- Department of Medicine, University of Otago Christchurch, Christchurch 8011, New Zealand
| | | | - Floris A. E. de Voogd
- Department of Paediatrics, University of Otago Christchurch, Christchurch 8011, New Zealand
- Department of Gastroenterology and Hepatology, Amsterdam UMC, 1105 Amsterdam, The Netherlands
| | | | - Steven T. Leach
- Department of Women’s and Children’s Health, University of New South Wales, Sydney 2052, Australia
| | - Daniel A. Lemberg
- Department of Women’s and Children’s Health, University of New South Wales, Sydney 2052, Australia
| | - Andrew S. Day
- Department of Paediatrics, University of Otago Christchurch, Christchurch 8011, New Zealand
- Department of Women’s and Children’s Health, University of New South Wales, Sydney 2052, Australia
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11
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Ge C, Lu Y, Shen H, Zhu L. Monitoring of intestinal inflammation and prediction of recurrence in ulcerative colitis. Scand J Gastroenterol 2022; 57:513-524. [PMID: 34994661 DOI: 10.1080/00365521.2021.2022193] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background and objectives: Ulcerative colitis is a chronic recurrent intestinal inflammatory disease, and its recurrence is difficult to predict. In this review, we summarized the objective indicators that can be used to evaluate intestinal inflammation, the purpose is to better predict the clinical recurrence of UC, formulate individualized treatment plan during remission of UC, and improve the level of diagnosis and treatment of UC.Methods: Based on the search results in the PUBMED database, we explored the accuracy and value of these methods in predicting the clinical recurrence of UC from the following three aspects: endoscopic and histological scores, serum biomarkers and fecal biomarkers.Results: Colonoscopy with biopsy is the gold standard for assessing intestinal inflammation, but it is invasive, inconvenient and expensive. At present, there is no highly sensitive and specific endoscopic or histological score to predict the clinical recurrence of UC. Compared with serum biomarkers, fecal biomarkers have higher sensitivity and specificity because they are in direct contact with the intestine and are closer to the site of intestinal inflammation. Fecal calprotectin is currently the most studied and meaningful fecal biomarker. Lactoferrin and S100A12, as novel biomarkers, have no better performance than FC in predicting the recurrence of UC.Conclusions: FC is currently the most promising predictive marker, but it lacks an accurate cut-off value. Combining patient symptoms, incorporating multiple indicators to construct a UC recurrence prediction model, and formulating individualized treatment plans for high recurrence risk patients will be the focus of UC remission management.
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Affiliation(s)
- Changchang Ge
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yi Lu
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Hong Shen
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lei Zhu
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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12
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Guo X, Huang C, Xu J, Xu H, Liu L, Zhao H, Wang J, Huang W, Peng W, Chen Y, Nie Y, Zhou Y, Zhou Y. Gut Microbiota Is a Potential Biomarker in Inflammatory Bowel Disease. Front Nutr 2022; 8:818902. [PMID: 35127797 PMCID: PMC8814525 DOI: 10.3389/fnut.2021.818902] [Citation(s) in RCA: 71] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 12/29/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is characterized by relapse and remission alternately. It remains a great challenge to diagnose and assess disease activity during IBD due to the lack of specific markers. While traditional biomarkers from plasma and stool, such as C-reactive protein (CRP), fecal calprotectin (FC), and S100A12, can be used to measure inflammation, they are not specific to IBD and difficult to determine an effective cut-off value. There is consensus that gut microbiota is crucial for intestinal dysbiosis is closely associated with IBD etiopathology and pathogenesis. Multiple studies have documented differences in the composition of gut microbiota between patients with IBD and healthy individuals, particularly regarding microbial diversity and relative abundance of specific bacteria. Patients with IBD have higher levels of Proteobacteria and lower amounts of Bacteroides, Eubacterium, and Faecalibacterium than healthy individuals. This review summarizes the pros and cons of using traditional and microbiota biomarkers to assess disease severity and treatment outcomes and addresses the possibility of using microbiota-focused interventions during IBD treatment. Understanding the role of microbial biomarkers in the assessment of disease activity and treatment outcomes has the potential to change clinical practice and lead to the development of more personalized therapies.
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Affiliation(s)
- Xue Guo
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Chen Huang
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Jing Xu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Haoming Xu
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Le Liu
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Hailan Zhao
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Jiaqi Wang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Wenqi Huang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Wu Peng
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Ye Chen
- Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Yuqiang Nie
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Yongjian Zhou
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Youlian Zhou
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
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13
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Aloi M, Cucchiara S. Crohn’s Disease. TEXTBOOK OF PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION 2022:379-391. [DOI: 10.1007/978-3-030-80068-0_28] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Wu T, Shi Y, Zhang Y, Zhang M, Zhang L, Ma Z, Zhao D, Wang L, Yu H, Hou Y, Gong J. Lactobacillus rhamnosus LB1 Alleviates Enterotoxigenic Escherichia coli-Induced Adverse Effects in Piglets by Improving Host Immune Response and Anti-Oxidation Stress and Restoring Intestinal Integrity. Front Cell Infect Microbiol 2021; 11:724401. [PMID: 34796123 PMCID: PMC8594739 DOI: 10.3389/fcimb.2021.724401] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 09/16/2021] [Indexed: 11/30/2022] Open
Abstract
Enterotoxigenic Escherichia coli (ETEC) is a common enteric pathogen that causes diarrhoea in humans and animals. Lactobacillus rhamnosus LB1 (formerly named Lactobacillus zeae LB1) has been shown to reduce ETEC infection to Caenorhabditis elegans and Salmonella burden in pigs. This study was to evaluate the effect of L. rhamnosus LB1 on the gut health of lactating piglets that were challenged with ETEC. Six-four piglets at 7 days of age were equally assigned into 8 groups (8 piglets per group): 1) control group (basal diet, phosphate buffer saline); 2) CT group (basal diet + 40 mg/kg colistin); 3) LL group (basal diet + 1 × 107 CFU/pig/day LB1); 4) HL group (basal diet + 1 × 108 CFU/pig/day LB1); 5) ETEC group: (basal diet + ETEC challenged); 6) CT + ETEC group (basal diet + CT + ETEC); 7) LL + ETEC group (basal diet + 1 × 107 CFU/pig/day LB1 + ETEC); 8) HL + ETEC group (basal diet + 1 × 108 CFU/pig/day LB1 + ETEC). The trial lasted ten days including 3 days of adaptation. Several significant interactions were found on blood parameters, intestinal morphology, gene, and protein expression. ETEC infection disrupted the cell structure and biochemical indicators of blood, undermined the integrity of the intestinal tract, and induced oxidative stress, diarrhoea, intestinal damage, and death of piglets. The supplementation of L. rhamnosus LB1 alleviated ETEC’s adverse effects by reducing pig diarrhoea, oxidative stress, and death, modulating cell structure and biochemical indicators of blood, improving the capacity of immunity and anti-oxidation stress of pigs, and restoring their intestinal integrity. At the molecular level, the beneficial effects of L. rhamnosus LB1 appeared to be mediated by regulating functional related proteins (including HSP70, Caspase-3, NLRP3, AQP3, and AQP4) and genes (including RPL4, IL-8, HP, HSP70, Mx1, Mx2, S100A12, Nrf2, GPX2 and ARG1). These results suggest that dietary supplementation of L. rhamnosus LB1 improved the intestinal functions and health of piglets.
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Affiliation(s)
- Tao Wu
- Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutrition Engineering, Wuhan Polytechnic University, Wuhan, China
| | - Yutao Shi
- Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutrition Engineering, Wuhan Polytechnic University, Wuhan, China
| | - Yanyan Zhang
- Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutrition Engineering, Wuhan Polytechnic University, Wuhan, China
| | - Min Zhang
- Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutrition Engineering, Wuhan Polytechnic University, Wuhan, China
| | - Lijuan Zhang
- Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutrition Engineering, Wuhan Polytechnic University, Wuhan, China
| | - Zhipeng Ma
- Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutrition Engineering, Wuhan Polytechnic University, Wuhan, China
| | - Di Zhao
- Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutrition Engineering, Wuhan Polytechnic University, Wuhan, China
| | - Lei Wang
- Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutrition Engineering, Wuhan Polytechnic University, Wuhan, China
| | - Hai Yu
- Guelph Research and Development Centre, Agriculture and Agri-Food Canada, Guelph, ON, Canada
| | - Yongqing Hou
- Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutrition Engineering, Wuhan Polytechnic University, Wuhan, China
| | - Joshua Gong
- Guelph Research and Development Centre, Agriculture and Agri-Food Canada, Guelph, ON, Canada
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Vernia F, Viscido A, Di Ruscio M, Stefanelli G, Valvano M, Latella G. Fecal Lactoferrin and Other Putative Fecal Biomarkers in Crohn's Disease: Do They Still Have a Potential Clinical Role? Digestion 2021; 102:833-844. [PMID: 34518458 DOI: 10.1159/000518419] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 07/11/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins. METHODS A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence. RESULTS The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data. CONCLUSIONS None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.
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Affiliation(s)
- Filippo Vernia
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Angelo Viscido
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Mirko Di Ruscio
- IBD Unit of IRCCS Ospedale Sacro Cuore - Don Calabria, Verona, Italy
| | - Gianpiero Stefanelli
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Marco Valvano
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
| | - Giovanni Latella
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, L'Aquila, Italy
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Abdehagh M, Azimirad M, Houri H, Nadalian B, Azimirad F, Olfatifar M, Nasir Shoeibi OK, Yadegar A, Shahrokh S, Mahdavi Roshan M, Asadzadeh Aghdaei H, Zali MR. Serum procalcitonin levels associate with Clostridioides difficile infection in patients with inflammatory bowel disease. BMC Infect Dis 2021; 21:1103. [PMID: 34702217 PMCID: PMC8549175 DOI: 10.1186/s12879-021-06804-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 10/20/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Clostridioides difficile infection (CDI) is a major cause of morbidity among patients with inflammatory bowel disease (IBD). Diagnostic biomarkers for early detection of CDI are needed in clinical practice. The relationship between serum procalcitonin and CDI in IBD patients has not been investigated so far. Therefore, we aimed to evaluate the usefulness of measuring serum procalcitonin level to detect CDI in patients with the flare of IBD. METHODS One hundred twenty patients with IBD were enrolled in this study. Bacterial identification was performed using standard microbiological and molecular methods. The serum procalcitonin levels were measured in all patients. Receiver operating characteristic (ROC) curve analysis was applied to assess the value of procalcitonin for the prediction of CDI among IBD patients. RESULTS The median serum procalcitonin level was significantly increased in IBD patients with CDI compared to non-CDI IBD patients (0.69 ng/mL vs 0.32 ng/mL). In univariate analysis, log10 procalcitonin was associated with CDI (OR 2.81, 95% CI 1.54-4.09, P-value < 0.001). Procalcitonin 1.1 ng/mL was 85% sensitive and 88% specific for the prediction of CDI. In the multivariable model including the covariates log10 procalcitonin, age, hospitalization, type of IBD, duration of the disease, and antibiotic usage, procalcitonin showed a robust association with CDI (OR 4.59, 95% CI 2.49-6.70, P-value < 0.001). An elevated procalcitonin level was associated with the presence of CDI among IBD patients. CONCLUSIONS Our results indicate that procalcitonin level can be a good candidate biomarker for assessing the CDI in IBD patients. Further studies are required to decipher whether procalcitonin can predict CDI therapy or its recurrence.
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Affiliation(s)
- Mohammad Abdehagh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamidreza Houri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Banafsheh Nadalian
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fahimeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Meysam Olfatifar
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ome Kolsoum Nasir Shoeibi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Shabnam Shahrokh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mehran Mahdavi Roshan
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Westerink F, Huibregtse I, De Hoog M, Bruin S, Meesters E, Brandjes D, Gerdes V. Faecal Inflammatory Biomarkers and Gastrointestinal Symptoms after Bariatric Surgery: A Longitudinal Study. Inflamm Intest Dis 2021; 6:109-116. [PMID: 34124182 DOI: 10.1159/000514576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 12/29/2020] [Indexed: 11/19/2022] Open
Abstract
Background Bariatric surgery induces various gastrointestinal (GI) modifications. We performed the first study longitudinally assessing the effect of bariatric surgery on faecal inflammatory biomarker levels and its relation with GI complaints. Method Faecal calprotectin, lactoferrin, and calgranulin-C levels were determined in 41 patients (34 Roux-en-Y [RYGB], 7 sleeves) before and at 6-16 weeks, 6 months, and 1 year after surgery. Changes in biomarker levels and percentage of patients above reference value were determined. Gastrointestinal symptom rating scale (GSRS) was used to assess GI complaints at corresponding time points. The postoperative relation between GSRS score and biomarker levels above reference value was investigated. Results After RYGB, median calprotectin levels are significantly higher (>188, 104-415 μg/g) than before surgery (40, 19-78 μg/g; p < 0.001), and over 90% of patients have levels above reference value 1 year after surgery. Median lactoferrin was 0.4 (0.2-1.6) μg/g before, and >5.9 (1.8-13.6) μg/g after surgery (p < 0.001). Median calgranulin-C levels remained far below the reference value and were 0.13 (0.05-0.24) μg/g before and <0.23 (0.06-0.33) μg/g after surgery. Similar results were found after sleeve gastrectomy. No difference was seen in GSRS score for patients with calprotectin and lactoferrin levels above reference values. Conclusion Faecal inflammatory biomarkers calprotectin and lactoferrin, but not calgranulin-C, rise above reference values shortly after bariatric surgery and remain elevated in the majority of patients. The discrepancy between calprotectin and calgranulin-C levels suggests no GI inflammation. Furthermore, patients after RYGB with biomarkers above the population reference value do not seem to have more GI complaints.
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Affiliation(s)
- Floris Westerink
- Department of internal medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Inge Huibregtse
- Department of gastroenterology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands
| | | | - Sjoerd Bruin
- Department of surgery, Spaarne Gasthuis, Hoofddorp, The Netherlands
| | - Eelco Meesters
- Department of internal medicine, Spaarne Gasthuis, Hoofddorp, The Netherlands
| | - Desiderius Brandjes
- Department of internal medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Victor Gerdes
- Department of internal medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands.,Department of internal medicine, Spaarne Gasthuis, Hoofddorp, The Netherlands
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Serum biomarkers confirming stable remission in inflammatory bowel disease. Sci Rep 2021; 11:6690. [PMID: 33758351 PMCID: PMC7988138 DOI: 10.1038/s41598-021-86251-w] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 03/11/2021] [Indexed: 12/15/2022] Open
Abstract
Crohn's disease (CD) and ulcerative colitis (UC) have a chronic-remittent course. Optimal management of inflammatory bowel diseases (IBD) relies on early intervention, treat-to-target strategies and a tight disease control. However, it is challenging to assess the risk of relapses in individual patients. We investigated blood-based biomarkers for the confirmation of disease remission in patients with IBD. We retrospectively analyzed samples of 40 IBD patients (30 UC, 10 CD) enrolled in a tight-control follow-up study. Half of the patients had a flare during follow up. Serum was analyzed for S100A12 as well as S100A8/A9 and for 50 further biomarkers in a bead-based multiplex assay. The concentrations of 9 cytokines/chemokines and S100A8/A9 significantly differed in IBD patients with unstable remission (before flares) when compared to IBD patients with stable remission. Although the number of patients was small, ROC curve analyses revealed a number of biomarkers (IL-1β, IL-1RA, IL-8, IL13, IL-15, IL-21, IL-25, IFN-β, CXCL9, CXCL10, CXCL11, Galectin-1, G-CSF and S100A8/A9) that were elevated in patients with later occurring relapses. While earlier studies on peripheral biomarkers in IBD are limited to only few analytes, our study using a broad screening approach identified serum biomarkers with the potential to indicate unstable disease control in IBD, which may help to steer individual therapies to maintain remission.
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Ramos SC, Jeong CD, Mamuad LL, Kim SH, Kang SH, Kim ET, Cho YI, Lee SS, Lee SS. Diet Transition from High-Forage to High-Concentrate Alters Rumen Bacterial Community Composition, Epithelial Transcriptomes and Ruminal Fermentation Parameters in Dairy Cows. Animals (Basel) 2021; 11:838. [PMID: 33809588 PMCID: PMC8002347 DOI: 10.3390/ani11030838] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/11/2021] [Accepted: 03/12/2021] [Indexed: 02/07/2023] Open
Abstract
Effects of changing diet on rumen fermentation parameters, bacterial community composition, and transcriptome profiles were determined in three rumen-cannulated Holstein Friesian cows using a 3 × 4 cross-over design. Treatments include HF-1 (first high-forage diet), HC-1 (first high-concentrate diet), HC-2 (succeeding high-concentrate diet), and HF-2 (second high-forage diet as a recovery period). Animal diets contained Klein grass and concentrate at ratios of 8:2, 2:8, 2:8, and 8:2 (two weeks each), respectively. Ammonia-nitrogen and individual and total volatile fatty acid concentrations were increased significantly during HC-1 and HC-2. Rumen species richness significantly increased for HF-1 and HF-2. Bacteroidetes were dominant for all treatments, while phylum Firmicutes significantly increased during the HC period. Prevotella, Erysipelothrix, and Galbibacter significantly differed between HF and HC diet periods. Ruminococcus abundance was lower during HF feeding and tended to increase during successive HC feeding periods. Prevotellaruminicola was the predominant species for all diets. The RNA sequence analysis revealed the keratin gene as differentially expressed during the HF diet, while carbonic-anhydrase I and S100 calcium-binding protein were expressed in the HC diet. Most of these genes were highly expressed for HC-1 and HC-2. These results suggested that ruminal bacterial community composition, transcriptome profile, and rumen fermentation characteristics were altered by the diet transitions in dairy cows.
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Affiliation(s)
- Sonny C. Ramos
- Ruminant Nutrition and Anaerobe Laboratory, Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea; (S.C.R.); (C.D.J.); (L.L.M.); (S.H.K.)
| | - Chang Dae Jeong
- Ruminant Nutrition and Anaerobe Laboratory, Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea; (S.C.R.); (C.D.J.); (L.L.M.); (S.H.K.)
| | - Lovelia L. Mamuad
- Ruminant Nutrition and Anaerobe Laboratory, Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea; (S.C.R.); (C.D.J.); (L.L.M.); (S.H.K.)
| | - Seon Ho Kim
- Ruminant Nutrition and Anaerobe Laboratory, Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea; (S.C.R.); (C.D.J.); (L.L.M.); (S.H.K.)
| | - Seung Ha Kang
- The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia;
| | - Eun Tae Kim
- Dairy Science Division, National Institute of Animal Science, Rural Development Administration, Cheonan 31000, Korea;
| | - Yong Il Cho
- Animal Disease and Diagnostic Laboratory, Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea;
| | - Sung Sill Lee
- Institute of Agriculture and Life Science and University-Centered Labs, Gyeongsang National University, Jinju 52828, Korea;
| | - Sang Suk Lee
- Ruminant Nutrition and Anaerobe Laboratory, Department of Animal Science and Technology, Sunchon National University, Suncheon 57922, Korea; (S.C.R.); (C.D.J.); (L.L.M.); (S.H.K.)
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A Review of Selected IBD Biomarkers: From Animal Models to Bedside. Diagnostics (Basel) 2021; 11:diagnostics11020207. [PMID: 33573291 PMCID: PMC7911946 DOI: 10.3390/diagnostics11020207] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 01/25/2021] [Accepted: 01/27/2021] [Indexed: 12/31/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a dysregulated inflammatory condition induced by multiple factors. The etiology of IBD is largely unknown, and the disease progression and prognosis are variable and unpredictable with uncontrolled disease behavior. Monitoring the status of chronic colitis closely is challenging for physicians, because the assessment of disease activity and severity require invasive methods. Using laboratory biomarkers may provide a useful alternative to invasive methods in the diagnosis and management of IBD. Furthermore, patients with ulcerative colitis or Crohn’s disease are also at risk of developing cancer. Annual colonoscopies can help lower the risk for developing colorectal cancer. However, laboratory biomarkers may also be helpful as non-invasive indicators in predicting treatment responses, improving prognosis, and predicting possible tumors. This review addresses selected laboratory biomarkers (including ANCA, chitinase 3-like 1, S100A12/RAGE, calprotectin, and TNF/TNFR2), which are identified by utilizing two well-accepted animal models of colitis, dextran sodium sulfate-induced and T cell receptor alpha knockout colitis models. In addition to being useful for monitoring disease severity, these biomarkers are associated with therapeutic strategies. The factors may regulate the initiation and perpetuation of inflammatory factors in the gut.
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Zhang C, Yao R, Chen J, Zou Q, Zeng L. S100 family members: potential therapeutic target in patients with hepatocellular carcinoma: A STROBE study. Medicine (Baltimore) 2021; 100:e24135. [PMID: 33546025 PMCID: PMC7837992 DOI: 10.1097/md.0000000000024135] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Accepted: 12/09/2020] [Indexed: 12/13/2022] Open
Abstract
Proteins in S100 family exhibit different expressions patterns and perform different cytological functions, playing substantial roles in certain cancers, carcinogenesis, and disease progression. However, the expression and role of S100 family members in the prognosis of hepatocellular carcinoma (HCC) remains unclear. To investigate the effect of S100 family members for the prognosis of liver cancer, we assessed overall survival (OS) using a Kaplan-Meier plotter (KM plotter) in liver cancer patients with different situation. Our results showed that 15 members of the S100 family exhibited high levels of expression and these levels were correlated with OS in liver cancer patients. The higher expression of S100A5, S100A7, S100A7A, S100A12, S100Z, and S100G was reflected with better survival in liver cancer patients. However, worse prognosis was related to higher levels of expression of S100A2, S100A6, S100A8, S100A9, S100A10, S100A11, S10013, S100A14, and S100P. We then evaluated the prognostic values of S100 family members expression for evaluating different stages of AJCC-T, vascular invasion, alcohol consumption, and the presence of hepatitis virus in liver cancer patients. Lastly, we studied the prognostic values of S100 family members expression for patients after sorafenib treatment. In conclusion, our findings show that the proteins of S100 family members exhibit differential expression and may be useful as targets for liver cancer, facilitating novel diagnostic and therapeutic strategies in cancer.
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Affiliation(s)
- Cai Zhang
- Department of Geriatrics, The People's Hospital of China Three Gorges University/The First People's Hospital of Yichang, Yichang
| | - Rucheng Yao
- Department of Hepatopancreatobilary Surgery, The First College of Clinical Medical Sciences, Three Gorges University, Yichang, Hubei
| | - Jie Chen
- Laboratory of Skeletal Development and Regeneration, Institute of Life Sciences, Chongqing Medical University, Chongqing, P.R. China
| | - Qiong Zou
- Department of Geriatrics, The People's Hospital of China Three Gorges University/The First People's Hospital of Yichang, Yichang
| | - Linghai Zeng
- Department of Geriatrics, The People's Hospital of China Three Gorges University/The First People's Hospital of Yichang, Yichang
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Liu F, Lee SA, Riordan SM, Zhang L, Zhu L. Global Studies of Using Fecal Biomarkers in Predicting Relapse in Inflammatory Bowel Disease. Front Med (Lausanne) 2020; 7:580803. [PMID: 33392214 PMCID: PMC7773777 DOI: 10.3389/fmed.2020.580803] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 12/01/2020] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract mainly comprising two forms including Crohn's disease (CD) and ulcerative colitis (UC). IBD is a lifelong relapsing remitting disease and relapses occur at random patterns which are unpredictable. Fecal biomarkers have been increasingly used to assess disease activity in IBD due to their positive correlations with intestinal inflammation. Recent studies have also assessed the use of fecal biomarkers in predicting relapse and post-operative recurrence. This review provides information from global studies of using fecal calprotectin, lactoferrin and S100A12 to predict relapse in IBD. Strategies for further studies and the use of these fecal biomarkers for personalized management in IBD are also discussed.
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Affiliation(s)
- Fang Liu
- Department of General Surgery and Central Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Seul A. Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Stephen M. Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, NSW, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Lixin Zhu
- Department of General Surgery and Central Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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Langhorst J, Kairey L, Oberle A, Boone J, Dobos G, Juette H, Tannapfel A, Rueffer A. Assessing Histological Inflammatory Activity in Patients With Ulcerative Colitis: A Diagnostic Accuracy Study Testing Fecal Biomarkers Lactoferrin and Calprotectin. CROHN'S & COLITIS 360 2020; 2:otaa053. [PMID: 36776494 PMCID: PMC9802191 DOI: 10.1093/crocol/otaa053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Indexed: 11/13/2022] Open
Abstract
Background and Aims Histological remission has arisen as the optimal treatment outcome in ulcerative colitis (UC). The aim of this retrospective study was to explore the diagnostic performance of the noninvasive fecal biomarkers calprotectin (FC) and lactoferrin (FL) compared to the histological indices Nancy Index (NI) and Riley Index (RI). Methods This study is a retrospective diagnostic accuracy study based on secondary analysis of patient data from 2002 to 2017 extracted from medical registries of our clinics in Essen-Mitte, Germany. Patients with UC underwent a colonoscopy, with biopsies taken from the rectum and the sigmoid scored by 2 experienced pathologists according to NI and RI and provided a stool sample within 7 days pre- or post-colonoscopy. Diagnostic accuracy of recommended cutoffs for FC (>50 μg/g) and FL (≥7.25 μg/g) were tested against our reference standard (NI ≥2) in terms of specificity, sensitivity, positive predictive value, negative predictive value, and accuracy (effectiveness). Results The number of patients with UC recruited was n = 226, aged 45.2 (SD 13.3). Histological indices were highly correlated (r = 0.980, P < 0.001). Fecal biomarkers correlated moderately with NI (FC: r = 0.383, P < 0.001; FL: r = 0.420, P < 0.001) and RI (FC: r = 0.395, P < 0.001; FL: r = 0.424, P < 0.001). Fecal biomarker concentrations were increased in patients with active histological disease (NI ≥2), median [IQR], FC 69.72 [20.07-254.38], FL 18.59 [6.06-44.42], compared to those with inactive disease (NI ≤1), FC 12.35 [3.89 - 32.16], FL 3.14 [0.75-11.05], z = -6.60, P < 0.001. Fecal biomarker concentrations differed significantly across NI grades 0-4 (FC: H4 = 45.2; FL: H4 = 47.5, both P < 0.001). Patients with grade 0 had significantly lower concentrations of fecal biomarkers than those with grade 3 (median; FC 10.94 vs 72.22; FL 2.30 vs 29.10; both P < 0.001) or grade 4 (FC 10.94 vs 67.00; FL 2.30 vs 27.64; both P < 0.001), as well as grade 2 for FC only (10.94 vs 56.22, P = 0.001). Concentrations were also lower in patients with grade 1 compared to those with grade 3 (FC 17.49 vs 72.22; FL 4.24 vs. 29.10; both P ≤ 0.001) or grade 4 (FC 17.49 vs 67.00; FL 4.24 vs 27.64; both P < 0.001).Receiver operating characteristics area under the curve showed moderate diagnostic accuracy for both FC 0.76 (95% confidence interval [CI] 0.70-0.83) and FL 0.73 (95% CI 0.66-0.80). Optimized cutoffs for both FC (≥34.29) and FL (≥5.85 μg/g) had slightly improved accuracy, compared with the manufacturer's cutoffs (FC: 69.9% vs 65.9%; FL: 71.7% vs 69.0%). Conclusions Fecal biomarkers calprotectin and lactoferrin correlate with histological disease activity and differentiate between patients in histological remission from those with evidence of moderate to severe disease activity. Their noninvasiveness, in addition to being inexpensive, supports their use in the clinical monitoring of patients with UC.
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Affiliation(s)
- Jost Langhorst
- Department of Internal and Integrative Medicine, Klinikum Bamberg, Bamberg, Germany,Chair for Integrative Medicine, University of Duisburg, Essen, Germany,Address correspondence to: Jost Langhorst, MD, Buger Str. 80, 96049 Bamberg, Germany ()
| | - Lana Kairey
- Department of Internal and Integrative Medicine, Klinikum Bamberg, Bamberg, Germany
| | - Angela Oberle
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
| | | | - Gustav Dobos
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany
| | - Hendrik Juette
- Institute for Pathology, Ruhr University Bochum, Bochum, Germany
| | - Andrea Tannapfel
- Institute for Pathology, Ruhr University Bochum, Bochum, Germany
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Li Y, Khamou M, Schaarschmidt BM, Umutlu L, Forsting M, Demircioglu A, Haubold J, Koch AK, Bruckmann NM, Sawicki LM, Herrmann K, Boone JH, Langhorst J. Comparison of 18F-FDG PET-MR and fecal biomarkers in the assessment of disease activity in patients with ulcerative colitis. Br J Radiol 2020; 93:20200167. [PMID: 32579403 DOI: 10.1259/bjr.20200167] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
OBJECTIVE To compare the diagnostic performance of fecal biomarkers and 18F-fludeoxyglucose (18F-FDG) positron emmision tomography-MR (PET-MR) in the assessment of disease activity in patients with ulcerative colitis. METHODS This study was conducted under the framework of a single-center clinical trial (clinicaltrials.gov [NCT03781284]). N = 50 participants were enrolled. Fecal samples were collected before bowel preparation. All patients underwent whole-body 18F-FDG PET-MR followed by ileocolonoscopy within 24 h. Diagnostic performance of five fecal biomarkers (calprotectin, lactoferrin, polymorphonuclear leukocyte elastase, S100A12 and eosinophil-derived neurotoxin), MR morphological parameters (MRmorph), diffusion-weighted imaging and PET in detecting active disease determined by Rachmilewitz endoscopic activity index (EAI) were evaluated and compared with each other. Correlations between fecal biomarkers, PET and endoscopy were calculated. RESULTS According to EAI, n = 38 patients presented with endoscopically active disease (16 mild, 19 moderate and 3 severe). All five biomarkers, PET and MRmorph could differentiate endoscopically active disease from endoscopic remission without significant difference regarding their operating characteristics (accuracies between 0.673 for calprotectin and 0.898 for lactoferrin). In predicting endoscopically moderate to severe disease, PET showed the highest diagnostic performance (accuracy = 0.857) compared to calprotectin and lactoferrin (accuracy = 0.633 and 0.735). PET had also the strongest correlation with endoscopy (ρ = 0.685, p < 0.001), while within fecal biomarkers the levels of lactoferrin and eosinophil-derived neurotoxin correlated significantly with EAI (ρ = 0.423 and 0.528, both p < 0.05). CONCLUSION Both fecal biomarkers and PET-MR were excellent non-invasive diagnostic tools in the assessment of disease activity in ulcerative colitis. ADVANCES IN KNOWLEDGE Both fecal biomarkers and PET-MR parameters are able to predict endoscopically active disease with comparable diagnostic performance. PET had the highest correlation with endoscopy and outperformed fecal biomarkers in differentiating moderate to severe from mild disease.
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Affiliation(s)
- Yan Li
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Michael Khamou
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Benedikt Michael Schaarschmidt
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Lale Umutlu
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Michael Forsting
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Aydin Demircioglu
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Johannes Haubold
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - Anna Katharina Koch
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, University of Duisburg-Essen, Am Deimelsberg 34a, 45276 Essen, Germany
| | - Nils-Martin Bruckmann
- Department of Diagnostic and Interventional Radiology, University Hospital Dusseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany
| | - Lino Morris Sawicki
- Department of Diagnostic and Interventional Radiology, University Hospital Dusseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany
| | - Ken Herrmann
- Department of Nuclear Medicine, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45147 Essen, Germany
| | - James Hunter Boone
- Research and Development, TechLab, INC., 2001 Kraft Drive, Blacksburg, USA
| | - Jost Langhorst
- Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, University of Duisburg-Essen, Am Deimelsberg 34a, 45276 Essen, Germany.,Department for Internal and Integrative Medicine, Social Foundation Bamberg, Clinic Bamberg, Buger Straße 80, 96049 Bamberg, Germany.,Chair for Integrative Medicine, University of Duisburg-Essen, Am Deimelsberg 34a, 45276 Essen, Germany
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Lu C, Liu J, Yao M, Li L, Li G. Downregulation of S100 calcium binding protein A12 inhibits the growth of glioma cells. BMC Cancer 2020; 20:261. [PMID: 32228516 PMCID: PMC7106817 DOI: 10.1186/s12885-020-06768-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 03/20/2020] [Indexed: 01/27/2023] Open
Abstract
Background S100 calcium binding protein A12 (S100A12) is a member of the S100 protein family and is widely expressed in neutrophil and low expressed in lymphocytes and monocyte. However, the role of S100A12 in glioma has not yet been identified. Methods In the present study, we carried out immunohistochemical investigation of S100A12 in 81 glioma tissues to determine the expression of S100A12 in glioma cells, and evaluate the clinical significance of S100A12 in glioma patients. Futher we knockdown the S100A12 by shRNA, and evaluated cell proliferation, cell migration and cell apoptosis by MTT, colony formation assay, transwell assay,flow cytometry assa and western blot. Results We found that S100A12 was upregulated in tissues of glioma patients and the expression was correlated to WHO stage and tumor size. Further, we found that knockdown S100A12 inhibits the proliferation, migration and invasion of glioma cells through regulating cell apoptosis and EMT. Conclusion S100A12 plays a vital role in glioma progression, and may be an important regulatory molecule for biological behaviors of glioma cell lines.
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Affiliation(s)
- Chunhe Lu
- Department of Neurosurgery, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang City, Liaoning Province, P.R. China, 110001
| | - Jia Liu
- Department of Neurosurgery, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang City, Liaoning Province, P.R. China, 110001
| | - Mingze Yao
- Department of Neurosurgery, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang City, Liaoning Province, P.R. China, 110001
| | - Lun Li
- Department of Neurosurgery, Anshan Hospital of the First Hospital of China Medical University, No.166,Minzhu Street,Tiexi District, Anshan, Liaoning Province, P.R. China, 110001
| | - Guangyu Li
- Department of Neurosurgery, The First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang City, Liaoning Province, P.R. China, 110001.
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Carvalho A, Lu J, Francis JD, Moore RE, Haley KP, Doster RS, Townsend SD, Johnson JG, Damo SM, Gaddy JA. S100A12 in Digestive Diseases and Health: A Scoping Review. Gastroenterol Res Pract 2020; 2020:2868373. [PMID: 32184815 PMCID: PMC7061133 DOI: 10.1155/2020/2868373] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 01/05/2020] [Accepted: 01/22/2020] [Indexed: 02/07/2023] Open
Abstract
Calgranulin proteins are an important class of molecules involved in innate immunity. These members of the S100 class of the EF-hand family of calcium-binding proteins have numerous cellular and antimicrobial functions. One protein in particular, S100A12 (also called EN-RAGE or calgranulin C), is highly abundant in neutrophils during acute inflammation and has been implicated in immune regulation. Structure-function analyses reveal that S100A12 has the capacity to bind calcium, zinc, and copper, processes that contribute to nutritional immunity against invading microbial pathogens. S100A12 is a ligand for the receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), and CD36, which promote cellular and immunological pathways to alter inflammation. We conducted a scoping review of the existing literature to define what is known about the association of S100A12 with digestive disease and health. Results suggest that S100A12 is implicated in gastroenteritis, necrotizing enterocolitis, gastritis, gastric cancer, Crohn's disease, irritable bowel syndrome, inflammatory bowel disease, and digestive tract cancers. Together, these results reveal S100A12 is an important molecule broadly associated with the pathogenesis of digestive diseases.
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Affiliation(s)
- Alexandre Carvalho
- Internal Medicine Program, St. Joseph Mercy Hospital, Ann Arbor, Michigan, USA
| | - Jacky Lu
- Department of Pathology, Microbiology, And Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Jamisha D. Francis
- Department of Pathology, Microbiology, And Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Rebecca E. Moore
- Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA
| | - Kathryn P. Haley
- Department of Biomedical Sciences, Grand Valley State University, Allendale, Michigan, USA
| | - Ryan S. Doster
- Department of Pathology, Microbiology, And Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Steven D. Townsend
- Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA
| | - Jeremiah G. Johnson
- Department of Microbiology, University of Tennessee, Knoxville, Tennessee, USA
| | - Steven M. Damo
- Department of Life and Physical Sciences, Fisk University, Nashville, Tennessee, USA
- Departments of Biochemistry and Chemistry, Vanderbilt University, Nashville, Tennessee, USA
- Department of Structural Biology, Vanderbilt University, Nashville, Tennessee, USA
| | - Jennifer A. Gaddy
- Department of Pathology, Microbiology, And Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Tennessee Valley Healthcare Systems, Department of Veterans Affairs, Nashville, Tennessee, USA
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Cording J, Blömacher M, Wiebe BI, Langhorst J, Kucharzik T, Sturm A, Schreiber S, Helwig U. Monitoring of Vedolizumab Infusion Therapy (MOVE-IT) Response With Fecal Inflammation Markers, Ultrasound, and Trough Serum Level in Patients With Ulcerative Colitis: Protocol for a Multicentric, Prospective, Noninterventional Study. JMIR Res Protoc 2019; 8:e14335. [PMID: 31702563 PMCID: PMC6874801 DOI: 10.2196/14335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 08/23/2019] [Accepted: 08/27/2019] [Indexed: 12/05/2022] Open
Abstract
Background Vedolizumab has been shown to induce clinical remission in patients with active ulcerative colitis. Treatment with anti-integrin vedolizumab leads to clinical remission in 16.9% and clinical response in 47.1% of cases after 6 weeks. However, in clinical practice, no decision to discontinue or continue vedolizumab therapy is made until 14 weeks at the earliest. Objective The aim of this study is to develop an algorithm for optimizing vedolizumab administration in patients with moderate-to-severe ulcerative colitis by calculating the probability of clinical response at week 14, on the basis of the data from week 6. Methods This is a prospective, single-arm, multicentric, noninterventional, observational study with no interim analyses and a sample size of 35 evaluable patients. Results The enrollment started in August 2018 and was still open at the date of submission. The study is expected to complete in September 2020. Conclusions The early identification of patients who are responding to an integrin antibody is therapeutically beneficial. At the same time, patients who are not responding can be identified earlier. The development of a therapeutic algorithm for identifying patients as responders or nonresponders can thus help prescribing physicians avoid ineffective treatments and stop these very early.
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Affiliation(s)
| | | | | | | | | | | | | | - Ulf Helwig
- University of Kiel, Kiel, Germany
- Medical Practice for Internal Medicine Oldenburg, Oldenburg, Germany
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Kato J, Yoshida T, Hiraoka S. Prediction of treatment outcome and relapse in inflammatory bowel disease. Expert Rev Clin Immunol 2019; 15:667-677. [PMID: 30873890 DOI: 10.1080/1744666x.2019.1593140] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Prediction of treatment outcome and clinical relapse in patients with inflammatory bowel disease (IBD), either ulcerative colitis (UC) or Crohn's disease (CD), is particularly important because therapeutics for IBD are not always effective and patients in remission could frequently relapse. Because undergoing endoscopy for the purpose is sometimes invasive and burdensome to patients, the performance of surrogate biomarkers has been investigated. Areas covered: We particularly featured the performance of patient symptoms, blood markers including C-reactive protein (CRP), fecal markers including fecal calprotectin (Fcal) and fecal immunochemical test (FIT) for prediction of endoscopic mucosal healing (MH) and prediction of relapse. Studies of other modalities and therapeutic drug monitoring (TDM) have also been explored. Expert opinion: Meticulous evaluation of patient symptoms could be predictive for MH in UC. CRP and Fcal may be accurate in prediction of MH of CD when MH is evaluated throughout the entire intestine including the small bowel. Repeated measurements of fecal markers including Fcal and FIT in patients with clinical remission would raise predictability of relapse. Prediction of treatment outcome by monitoring with blood markers including CRP, fecal markers including Fcal, and TDM has frequently been performed in recent clinical trials and shown to be effective.
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Affiliation(s)
- Jun Kato
- a Department of Gastroenterology , Mitsui Memorial Hospital , Tokyo , Japan
| | - Takeichi Yoshida
- b Second Department of Internal Medicine , Wakayama Medical University , Wakayama , Japan
| | - Sakiko Hiraoka
- c Department of Gastroenterology and Hepatology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
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Nanini HF, Bernardazzi C, Castro F, de Souza HSP. Damage-associated molecular patterns in inflammatory bowel disease: From biomarkers to therapeutic targets. World J Gastroenterol 2018; 24:4622-4634. [PMID: 30416310 PMCID: PMC6224468 DOI: 10.3748/wjg.v24.i41.4622] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 10/08/2018] [Accepted: 10/16/2018] [Indexed: 02/06/2023] Open
Abstract
The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. These components include environmental elements and gut microbiota a dysbiosis. For decades, immune abnormalities have been investigated as critically important in IBD pathogenesis, and attempts to develop effective therapies have predominantly targeted the immune system. Nevertheless, immune events represent only one of the constituents contributing to IBD pathogenesis within the context of the complex cellular and molecular network underlying chronic intestinal inflammation. These factors need to be appreciated within the milieu of non-immune components. Damage-associated molecular patterns (DAMPs), which are essentially endogenous stress proteins expressed or released as a result of cell or tissue damage, have been shown to act as direct pro-inflammatory mediators. Excessive or persistent signalling mediated by such molecules can underlie several chronic inflammatory disorders, including IBD. The release of endogenous DAMPs amplifies the inflammatory response driven by immune and non-immune cells and promotes epigenetic reprogramming in IBD. The effects determine pathologic changes, which may sustain chronic intestinal inflammation and also underlie specific disease phenotypes. In addition to highlighting the potential use of DAMPs such as calprotectin as biomarkers, research on DAMPs may reveal novel mechanistic associations in IBD pathogenesis and is expected to uncover putative therapeutic targets.
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Affiliation(s)
- Hayandra Ferreira Nanini
- Serviço de Gastroenterologia e Laboratório Multidisciplinar de Pesquisa, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil
| | - Claudio Bernardazzi
- Serviço de Gastroenterologia e Laboratório Multidisciplinar de Pesquisa, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil
| | - Fernando Castro
- Serviço de Gastroenterologia e Laboratório Multidisciplinar de Pesquisa, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil
| | - Heitor Siffert Pereira de Souza
- Serviço de Gastroenterologia e Laboratório Multidisciplinar de Pesquisa, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil
- D’Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro, RJ 22281-100, Brazil
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30
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Zhong K, Zhang C, Zha G, Wang X, Jiao X, Zhu H, Wang Y. S100 calcium‐binding protein A12 as a diagnostic index for subclinical mastitis in cows. Reprod Domest Anim 2018; 53:1442-1447. [DOI: 10.1111/rda.13273] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Accepted: 06/29/2018] [Indexed: 01/25/2023]
Affiliation(s)
- Kai Zhong
- Key Laboratory of Animal Biochemistry and Nutrition Ministry of Agriculture College of Animal Science and Verterinary Medicine Henan Agricultural University Zhengzhou Henan China
| | - Cheng‐yu Zhang
- Key Laboratory of Animal Biochemistry and Nutrition Ministry of Agriculture College of Animal Science and Verterinary Medicine Henan Agricultural University Zhengzhou Henan China
| | - Guang‐ming Zha
- Key Laboratory of Animal Biochemistry and Nutrition Ministry of Agriculture College of Animal Science and Verterinary Medicine Henan Agricultural University Zhengzhou Henan China
| | - Xin‐jian Wang
- Key Laboratory of Animal Biochemistry and Nutrition Ministry of Agriculture College of Animal Science and Verterinary Medicine Henan Agricultural University Zhengzhou Henan China
| | - Xian‐qin Jiao
- Key Laboratory of Animal Biochemistry and Nutrition Ministry of Agriculture College of Animal Science and Verterinary Medicine Henan Agricultural University Zhengzhou Henan China
| | - He‐shui Zhu
- Key Laboratory of Animal Biochemistry and Nutrition Ministry of Agriculture College of Animal Science and Verterinary Medicine Henan Agricultural University Zhengzhou Henan China
| | - Yue‐ying Wang
- Key Laboratory of Animal Biochemistry and Nutrition Ministry of Agriculture College of Animal Science and Verterinary Medicine Henan Agricultural University Zhengzhou Henan China
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31
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Diagnostic Markers for Nonspecific Inflammatory Bowel Diseases. DISEASE MARKERS 2018; 2018:7451946. [PMID: 29991970 PMCID: PMC6016179 DOI: 10.1155/2018/7451946] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Revised: 04/18/2018] [Accepted: 05/16/2018] [Indexed: 12/13/2022]
Abstract
The nonspecific inflammatory bowel diseases (IBD) represent a heterogeneous group of chronic inflammatory disorders of the gastrointestinal tract, and Leśniowski-Crohn's disease (CD) and ulcerative colitis (UC) are among the two major clinical forms. Despite the great progress in understanding the pathogenesis of these diseases, their etiology remains unclear. Genetic, immune, and environmental factors are thought to play a key role. The correct diagnosis of nonspecific inflammatory bowel diseases as well as the determination of disease activity, risk stratification, and prediction of response to therapy still relies on a multidisciplinary approach based on clinical, laboratory, endoscopic, and histologic examination. However, considerable effort has been devoted to the development of an accurate panel of noninvasive biomarkers that have increased diagnostic sensitivity and specificity. Laboratory biomarkers useful in differentiating IBD with functional disorders and in evaluating disease activity, prognosis, and treatment selection for IBD are presented in this study.
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Hanifeh M, Sankari S, Rajamäki MM, Syrjä P, Kilpinen S, Suchodolski JS, Heilmann RM, Guadiano P, Lidbury J, Steiner JM, Spillmann T. S100A12 concentrations and myeloperoxidase activities are increased in the intestinal mucosa of dogs with chronic enteropathies. BMC Vet Res 2018; 14:125. [PMID: 29618371 PMCID: PMC5885293 DOI: 10.1186/s12917-018-1441-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2017] [Accepted: 03/22/2018] [Indexed: 01/14/2023] Open
Abstract
Background Intestinal mucosal S100A12 and myeloperoxidase (MPO) are inflammatory biomarkers in humans with inflammatory bowel disease (IBD). However, these biomarkers have not been studied in the intestinal mucosa of dogs with chronic enteropathies (CE), even though dogs with CE have increased S100A12 concentrations in feces and serum. This study investigated mucosal S100A12 concentrations and MPO activities in both dogs with CE and healthy Beagles. ELISA (S100A12 concentrations) and spectrophotometric methods (MPO activity) were used. The associations of both biomarkers with canine IBD activity index (CIBDAI), histopathologic findings, clinical outcome, and serum albumin concentrations were also investigated. We studied intestinal mucosal samples originating from different intestinal regions of 40 dogs with CE and 18 healthy Beagle dogs (duodenum, ileum, colon, and cecum). Results Compared with healthy Beagles, mucosal S100A12 concentrations in dogs with CE were significantly higher in the duodenum (p < 0.0001) and colon (p = 0.0011), but not in the ileum (p = 0.2725) and cecum (p = 0.2194). Mucosal MPO activity of dogs with CE was significantly higher in the duodenum (p < 0.0001), ileum (p = 0.0083), colon (p < 0.0001), and cecum (p = 0.0474). Mucosal S100A12 concentrations in the duodenum were significantly higher if the inflammatory infiltrate consisted mainly of neutrophils (p = 0.0439) or macrophages (p = 0.037). Mucosal S100A12 concentrations also showed a significant association with the severity of total histopathological injury and epithelial injury in the colon (p < 0.05). Mucosal MPO activity showed a significant association (p < 0.05) with the severity of total histopathological injury, epithelial injury, and eosinophil infiltration in the duodenum. There was no significant association of both biomarkers with CIBDAI or clinical outcome. Conclusions This study showed that both mucosal S100A12 concentrations and MPO activities are significantly increased in the duodenum and colon of dogs with CE; mucosal MPO was also increased in the ileum and cecum. Future research should focus on assessing the clinical utility of S100A12 and MPO as diagnostic markers in dogs with CE.
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Affiliation(s)
- Mohsen Hanifeh
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, PO Box 57, Viikintie 49, 00014, Helsinki, Finland. .,Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, 5166616471, Iran.
| | - Satu Sankari
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, PO Box 57, Viikintie 49, 00014, Helsinki, Finland
| | - Minna M Rajamäki
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, PO Box 57, Viikintie 49, 00014, Helsinki, Finland
| | - Pernilla Syrjä
- Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, PO Box 66, Agnes Sjöberginkatu 2, 00014, Helsinki, Finland
| | - Susanne Kilpinen
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, PO Box 57, Viikintie 49, 00014, Helsinki, Finland
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4474, USA
| | - Romy M Heilmann
- Department of Small Animal Medicine, Veterinary Teaching Hospital, University of Leipzig, An den Tierkliniken 23, 04103, Leipzig, SN, Germany
| | - Phillip Guadiano
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4474, USA
| | - Jonathan Lidbury
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4474, USA
| | - Jörg M Steiner
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4474, USA
| | - Thomas Spillmann
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, PO Box 57, Viikintie 49, 00014, Helsinki, Finland
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Shores DR, Everett AD. Children as Biomarker Orphans: Progress in the Field of Pediatric Biomarkers. J Pediatr 2018; 193:14-20.e31. [PMID: 29031860 PMCID: PMC5794519 DOI: 10.1016/j.jpeds.2017.08.077] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 08/04/2017] [Accepted: 08/30/2017] [Indexed: 12/20/2022]
Affiliation(s)
- Darla R Shores
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD.
| | - Allen D Everett
- Division of Cardiology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD
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Galgut BJ, Lemberg DA, Day AS, Leach ST. The Value of Fecal Markers in Predicting Relapse in Inflammatory Bowel Diseases. Front Pediatr 2018; 5:292. [PMID: 29404311 PMCID: PMC5780398 DOI: 10.3389/fped.2017.00292] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Accepted: 12/20/2017] [Indexed: 12/12/2022] Open
Abstract
The inflammatory bowel diseases (IBDs) are lifelong chronic illnesses that place an immense burden on patients. The primary aim of therapy is to reduce disease burden and prevent relapse. However, the occurrence of relapses is often unpredictable. Current disease monitoring is primarily by way of clinical indices, with relapses often only recognized once the inflammatory episode is established with subsequent symptoms and gut damage. The window between initial upregulation of the inflammatory response and the recognition of symptoms may provide an opportunity to prevent the relapse and associated morbidity. This review will describe the existing literature surrounding predictive indicators of relapse of IBD with a specific focus on fecal biomarkers. Fecal biomarkers offer promise as a convenient, non-invasive, low cost option for disease monitoring that is predictive of subsequent relapse. To exploit the potential of fecal biomarkers in this role, further research is now required. This research needs to assess multiple fecal markers in context with demographics, disease phenotype, genetics, and intestinal microbiome composition, to build disease behavior models that can provide the clinician with sufficient confidence to intervene and change the long-term disease course.
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Affiliation(s)
- Bianca J. Galgut
- School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW, Australia
| | - Daniel A. Lemberg
- School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW, Australia
- Department of Gastroenterology, Sydney Children’s Hospital Randwick, Sydney, NSW, Australia
| | - Andrew S. Day
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Steven T. Leach
- School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW, Australia
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Wędrychowicz A, Tomasik P, Zając A, Fyderek K. Prognostic value of assessment of stool and serum IL-1β, IL-1ra and IL-6 concentrations in children with active and inactive ulcerative colitis. Arch Med Sci 2018; 14:107-114. [PMID: 29379540 PMCID: PMC5778426 DOI: 10.5114/aoms.2017.68696] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 06/05/2017] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1ra) and interleukin-6 (IL-6) contribute to the pathogenesis of ulcerative colitis (UC). The aim of our study was to evaluate the serum and stool IL-1β, IL-1ra and IL-6 concentrations as potential prognostic factors in children with UC. MATERIAL AND METHODS Thirty-eight children with UC (20 active, 18 inactive) and 14 healthy controls were prospectively included in the study. IL-1β, IL-1ra and IL-6 concentrations were measured in serum and stool supernatants at inclusion to the study using ELISA immunoassays. The children were followed up over 5 years, and at each follow-up clinical disease activity, quantity and severity of relapses, nutritional status, endoscopic and histopathologic activity, disease complications and the treatment regimen were evaluated. RESULTS In children with active and inactive UC who had relapsed during a 5-year follow-up period compared to the non-relapse groups we found significantly increased serum IL-1β (1.34 vs. 0.98 pg/ml, p < 0.05, and 1.02 vs. 0.68 pg/ml, p < 0.01, respectively,) and IL-1ra (718.0 vs. 453.2 pg/ml, p < 0.05, and 567.4 vs. 365.1 pg/ml, p < 0.01, respectively). Additionally, in children who had experienced complications during a 5-year follow-up period we observed significantly increased serum and stool IL-1β (p < 0.05) and serum IL-1ra (p < 0.01) compared to the group without complications. CONCLUSIONS We concluded that serum IL-1β and IL-1ra and to a lesser extend stool IL-1β concentrations may be useful prognostic factors in children with active and inactive UC over a short-term follow-up period, which may help to identify children that require more aggressive therapy due to an increased risk of relapse or complications resulting from UC.
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Affiliation(s)
- Andrzej Wędrychowicz
- Department of Pediatrics, Gastroenterology and Nutrition, Jagiellonian University Medical College, Krakow, Poland
| | - Przemysław Tomasik
- Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland
| | - Andrzej Zając
- Department of Pediatric Surgery, Jagiellonian University Medical College, Krakow, Poland
| | - Krzysztof Fyderek
- Department of Pediatrics, Gastroenterology and Nutrition, Jagiellonian University Medical College, Krakow, Poland
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Di Ruscio M, Vernia F, Ciccone A, Frieri G, Latella G. Surrogate Fecal Biomarkers in Inflammatory Bowel Disease: Rivals or Complementary Tools of Fecal Calprotectin? Inflamm Bowel Dis 2017; 24:78-92. [PMID: 29272479 DOI: 10.1093/ibd/izx011] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Current noninvasive methods for assessing intestinal inflammation in inflammatory bowel disease (IBD) remain unsatisfactory. Along with C-reactive protein and erythrocyte sedimentation rate, fecal calprotectin (FC) is the standard test for assessing IBD activity, even though its specificity and accuracy are not optimal and it lacks a validated cutoff. Over the past few decades, several fecal markers released from intestinal inflammatory cells have been investigated in IBD; they are the subject of this systematic review. METHODS A systematic electronic search of the English literature up to April 2017 was performed using Medline and the Cochrane Library. Only papers written in English that analyzed fecal biomarkers in IBD were included. In vitro studies, animal studies, studies on blood/serum samples, and studies analyzing FC or fecal lactoferrin alone were excluded. RESULTS Out of 1023 citations, 125 eligible studies were identified. Data were grouped according to each fecal marker including S100A12, high-mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, human neutrophil peptides, neutrophil gelatinase-associated lipocalin, chitinase 3-like-1, matrix metalloproteinase 9, lysozyme, M2-pyruvate kinase, myeloperoxidase, fecal eosinophil proteins, human beta-defensin-2, and beta-glucuronidase. Some of these markers showed a high sensitivity and specificity and correlated with disease activity, response to therapy, and mucosal healing. Furthermore, they showed a potential utility in the prediction of clinical relapse. CONCLUSIONS Several fecal biomarkers have the potential to become useful tools complementing FC in IBD diagnosis and monitoring. However, wide variability in their accuracy in assessment of intestinal inflammation suggests the need for further studies.
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Affiliation(s)
- Mirko Di Ruscio
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, Coppito, L'Aquila, Italy
| | - Filippo Vernia
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, Coppito, L'Aquila, Italy
| | - Antonio Ciccone
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, Coppito, L'Aquila, Italy
| | - Giuseppe Frieri
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, Coppito, L'Aquila, Italy
| | - Giovanni Latella
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, Piazza S. Tommasi, Coppito, L'Aquila, Italy
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Andersson E, Bergemalm D, Kruse R, Neumann G, D’Amato M, Repsilber D, Halfvarson J. Subphenotypes of inflammatory bowel disease are characterized by specific serum protein profiles. PLoS One 2017; 12:e0186142. [PMID: 28982144 PMCID: PMC5628935 DOI: 10.1371/journal.pone.0186142] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 09/26/2017] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE Genetic and immunological data indicate that inflammatory bowel disease (IBD) are characterized by specific inflammatory protein profiles. However, the serum proteome of IBD is still to be defined. We aimed to characterize the inflammatory serum protein profiles of Crohn's disease (CD) and ulcerative colitis (UC), using the novel proximity extension assay. METHODS A panel of 91 inflammatory proteins were quantified in a discovery cohort of CD (n = 54), UC patients (n = 54), and healthy controls (HCs; n = 54). We performed univariate analyses by t-test, with false discovery rate correction. A sparse partial least-squares (sPLS) approach was used to identify additional discriminative proteins. The results were validated in a replication cohort. RESULTS By univariate analysis, 17 proteins were identified with significantly different abundances in CD and HCs, and 12 when comparing UC and HCs. Additionally, 64 and 45 discriminant candidate proteins, respectively, were identified with the multivariate approach. Correspondingly, significant cross-validation error rates of 0.12 and 0.19 were observed in the discovery cohort. Only FGF-19 was identified from univariate comparisons of CD and UC, but 37 additional discriminant candidates were identified using the multivariate approach. The observed cross-validation error rate for CD vs. UC remained significant when restricting the analyses to patients in clinical remission. Using univariate comparisons, 16 of 17 CD-associated proteins and 8 of 12 UC-associated proteins were validated in the replication cohort. The area under the curve for CD and UC was 0.96 and 0.92, respectively, when the sPLS model from the discovery cohort was applied to the replication cohort. CONCLUSIONS By using the novel PEA method and a panel of inflammatory proteins, we identified proteins with significantly different quantities in CD patients and UC patients compared to HCs. Our data highlight the potential of the serum IBD proteome as a source for identification of future diagnostic biomarkers.
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Affiliation(s)
- Erik Andersson
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Daniel Bergemalm
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Robert Kruse
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Gunter Neumann
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Mauro D’Amato
- Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- BioDonostia Health Research Institute, San Sebastian, Spain
- IKERBASQUE Basque Foundation for Science, Bilbao, Spain
| | - Dirk Repsilber
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
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Day AS, Leach ST, Lemberg DA. An update on diagnostic and prognostic biomarkers in inflammatory bowel disease. Expert Rev Mol Diagn 2017; 17:835-843. [PMID: 28770636 DOI: 10.1080/14737159.2017.1364160] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Diagnosis of the chronic inflammatory bowel diseases relies upon initial recognition of an inflammatory condition, followed by definitive endoscopic, histological and radiological investigations. Various biomarkers are available to assist with initial elucidation of an inflammatory process: these also have important roles after diagnosis in monitoring and ongoing assessment of progress. Areas covered: Various inflammatory markers, serological tests and genetic analyses may be helpful in predicting the course of disease in the coming months. This review provides an update on the current understanding and knowledge about these markers. It also highlights key gaps and identifies aspects that require further study. Expert commentary: Our current approach to the application of non-invasive biomarkers is rudimentary. Further work is required to elucidate the roles of the various markers.
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Affiliation(s)
- Andrew S Day
- a Department of Paediatrics , University of Otago (Christchurch) , Christchurch , New Zealand
- b School of Women's and Children's Health , University of New South Wales , Sydney , Australia
| | - Steven T Leach
- b School of Women's and Children's Health , University of New South Wales , Sydney , Australia
| | - Daniel A Lemberg
- b School of Women's and Children's Health , University of New South Wales , Sydney , Australia
- c Department of Paediatric Gastroenterology , Sydney Children's Hospital , Sydney , Australia
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Whitehead SJ, Ford C, Gama RM, Ali A, McKaig B, Waldron JL, Steed H, Brookes MJ. Effect of faecal calprotectin assay variability on the management of inflammatory bowel disease and potential role of faecal S100A12. J Clin Pathol 2017; 70:1049-1056. [DOI: 10.1136/jclinpath-2017-204340] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Revised: 04/17/2017] [Accepted: 04/18/2017] [Indexed: 02/06/2023]
Abstract
AimsTo prospectively evaluate whether between-assay variability of different faecal calprotectin (f-Cp) assays influences diagnostic accuracy for inflammatory bowel disease (IBD) in a cohort of patients with confirmed IBD and irritable bowel syndrome (IBS). To also evaluate the diagnostic accuracy of faecal S100A12 (f-S100A12) against f-Cp in the same patient cohort and assess whether f-S100A12 offers additional diagnostic value.MethodsF-Cp using four commercially available f-Cp assays, f-S100A12 and blood biomarkers were measured in patients, recruited from the local IBD clinic, who had established IBS or active ulcerative colitis (UC) and Crohn’s disease (CD). Diagnostic sensitivities and specificities for each assay and biomarker were calculated and compared.ResultsMedian f-Cp levels in all assays were significantly higher in UC (347–884 µg/g; n=28) and CD (377–838 µg/g; n=15) compared with IBS (6–27 µg/g; n=17). Sensitivities and specificities at 50 µg/g were 94%–100% and 82%–100%, respectively. Median f-S100A12 levels were significantly higher in UC (81.0 µg/g; IQR 38.3–159.8) and CD (47.2 µg/g; IQR 5.3–108.9) compared with IBS (0.7 µg/g; IQR 0.5–0.8). At 2.8 µg/g, f-S100A12 had a sensitivity of 97% and specificity of 94%. The blood biomarkers demonstrated sensitivities and specificities of 44%–63% and 80%–92%, respectively.ConclusionsThe diagnostic sensitivity of the calprotectin assays was similar despite inter-kit variability in absolute values. There is a need for f-Cp assay standardisation, but in its absence assay-specific cut-off values may optimise their diagnostic performance. F-S100A12 demonstrated comparable sensitivity and specificity to f-Cp and although a research tool at present, may have a future role to play in the diagnosis and management of these patients.
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Day AS, Adamji M. Commentary: Impact of Fecal Calprotectin Measurement on Decision-Making in Children with Inflammatory Bowel Disease. Front Pediatr 2017; 5:133. [PMID: 28634577 PMCID: PMC5459887 DOI: 10.3389/fped.2017.00133] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Accepted: 05/22/2017] [Indexed: 01/15/2023] Open
Affiliation(s)
- Andrew S. Day
- Department of Paediatrics, Christchurch Hospital, Christchurch, New Zealand
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Mustafa Adamji
- Department of Paediatrics, Christchurch Hospital, Christchurch, New Zealand
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Clinical Utility of Fecal Calprotectin Monitoring in Asymptomatic Patients with Inflammatory Bowel Disease: A Systematic Review and Practical Guide. Inflamm Bowel Dis 2017; 23:894-902. [PMID: 28511198 PMCID: PMC5434712 DOI: 10.1097/mib.0000000000001082] [Citation(s) in RCA: 114] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND In asymptomatic patients with inflammatory bowel disease (IBD), "monitoring" involves repeated testing aimed at early recognition of disease exacerbation. We aimed to determine the usefulness of repeated fecal calprotectin (FC) measurements to predict IBD relapses by a systematic literature review. METHODS An electronic search was performed in Medline, Embase, and Cochrane from inception to April 2016. Inclusion criteria were prospective studies that followed patients with IBD in remission at baseline and had at least 2 consecutive FC measurements with a test interval of 2 weeks to 6 months. Methodological assessment was based on the second Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. RESULTS A total of 1719 articles were identified; 193 were retrieved for full text review. Six studies met eligibility for inclusion. The time interval between FC tests varied between 1 and 3 months. Asymptomatic patients with IBD who had repeated FC measurements above the study's cutoff level had a 53% to 83% probability of developing disease relapse within the next 2 to 3 months. Patients with repeated normal FC values had a 67% to 94% probability to remain in remission in the next 2 to 3 months. The ideal FC cutoff for monitoring could not be identified because of the limited number studies meeting inclusion criteria and heterogeneity between selected studies. CONCLUSIONS Two consecutively elevated FC values are highly associated with disease relapse, indicating a consideration to proactively optimize IBD therapy plans. More prospective data are necessary to assess whether FC monitoring improves health outcomes.
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Siddiqui I, Majid H, Abid S. Update on clinical and research application of fecal biomarkers for gastrointestinal diseases. World J Gastrointest Pharmacol Ther 2017; 8:39-46. [PMID: 28217373 PMCID: PMC5292605 DOI: 10.4292/wjgpt.v8.i1.39] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Revised: 12/13/2016] [Accepted: 01/02/2017] [Indexed: 02/07/2023] Open
Abstract
Gastrointestinal (GI) diseases comprise a large spectrum of clinical conditions ranging from indigestion to inflammatory bowel diseases (IBDs) and carcinomas. Endoscopy is the usual method employed to diagnose these condition. Another noninvasive way to assess and diagnose GI conditions are fecal biomarkers. Fecal biomarkers provide information regarding a specific disease process and are perhaps more acceptable to clinicians and patients alike because of their non-invasivity compared to endoscopy. Aim of this review was to evaluate the current status of the fecal biomarkers in clinical and research for in GI diseases. Multiple types of fecal biomarkers are discussed in this review including; markers to assess IBD, which are released as a results of an inflammatory insults to intestinal epithelia such as antimicrobial peptides (lactoferrin) or inflammation related proteins (calprotectin). While markers related to function of digestion are primarily related to partially digested food or mucosal proteins such as abnormal amount of fecal fat α1-antitrypsin, elastase and secretary IgA. The upcoming fecal biomarker like M2 pyruvate kinase and neutrophil gelatinase associated lipocalin are discussed as well. Apart from above mention, the fecal biomarkers under exploration for possible clinical use in future are also discussed. These include cathelicidins, osteoprotegerin, β-glucuronidase, Eosinophil proteins, etc.
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Zhang Y, Wang PX, Zhang HJ. Role of biomarkers in diagnosis and evaluation of disease activity of Crohn's disease. Shijie Huaren Xiaohua Zazhi 2016; 24:4389-4395. [DOI: 10.11569/wcjd.v24.i32.4389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Crohn's disease (CD) is a group of chronic, relapsing inflammatory gastrointestinal diseases with unknown etiology. The goals of treatment are to induce the transition from active stage into inactive stage and to maintain remission. Therefore, it is important to diagnose and assess disease activity in patients with CD. Recently, noninvasive markers for intestinal inflammation have been wildly adopted in clinical practice in order to differentiate CD from other diseases, to grade inflammation, to assess the response to therapy, and to demonstrate recurrent inflammation after medical or surgically-induced remission. Fecal and serum calprotectins are among the best-studied noninvasive biomarkers of inflammation in CD which have attracted clinicians' attention. This paper gives an overview of the clinical implications of biomarkers for diagnosing and monitoring disease activity of CD.
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Abstract
Inflammatory disorders of childhood, such as juvenile idiopathic arthritis (JIA) and inflammatory bowel disease (IBD) are a challenge for laboratory diagnostics. Firstly, the classical inflammatory markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) often inadequately reflect disease activity but on the other hand there are few specific biomarkers that can be helpful in managing these diseases. Acute phase proteins reflect the systemic inflammatory response insufficiently as their increase is only the indirect result of local inflammatory processes. Modern inflammation diagnostics aim to reflect these local processes and to allow precise monitoring of disease activity. Experimental biomarkers, such as S100 proteins can detect subclinical inflammatory activity. In addition, established laboratory parameters exist for JIA [antinuclear antibodies (ANA), rheumatoid factor (RF), antibodies against cyclic citrullinated peptide (anti-CCP)] and for chronic IBD (fecal calprotectin) that are useful in the treatment of these diseases.
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Utility of surrogate markers for the prediction of relapses in inflammatory bowel diseases. J Gastroenterol 2016; 51:531-47. [PMID: 26975751 DOI: 10.1007/s00535-016-1191-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Accepted: 02/21/2016] [Indexed: 02/04/2023]
Abstract
Patients with diagnosed inflammatory bowel disease (IBD) will commonly experience a clinical relapse in spite of a prolonged therapy-induced period of clinical remission. The current methods of assessing subclinical levels of low-grade inflammation which predispose patients to relapse are not optimal when considering both cost and patient comfort. Over the past few decades, much investigation has discovered that proteins such as calprotectin that are released from inflammatory cells are capable of indicating disease activity. Along with C-reactive protein and erythrocyte sedimentation rate, calprotectin has now become part of the current methodology for assessing IBD activity. More recently, research has identified that other fecal and serum biomarkers such as lactoferrin, S100A12, GM-CSF autoantibodies, α1-antitrypsin, eosinophil-derived proteins, and cytokine concentrations have variable degrees of utility in monitoring gastrointestinal tract inflammation. In order to provide direction toward novel methods of predicting relapse in IBD, we provide an up-to-date review of these biomarkers and their potential utility in the prediction of clinical relapse, given their observed activities during various stages of clinical remission.
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46
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Boyapati RK, Rossi AG, Satsangi J, Ho GT. Gut mucosal DAMPs in IBD: from mechanisms to therapeutic implications. Mucosal Immunol 2016; 9:567-82. [PMID: 26931062 DOI: 10.1038/mi.2016.14] [Citation(s) in RCA: 113] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2015] [Accepted: 12/31/2015] [Indexed: 02/06/2023]
Abstract
Endogenous damage-associated molecular patterns (DAMPs) are released during tissue damage and have increasingly recognized roles in the etiology of many human diseases. The inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), are immune-mediated conditions where high levels of DAMPs are observed. DAMPs such as calprotectin (S100A8/9) have an established clinical role as a biomarker in IBD. In this review, we use IBD as an archetypal common chronic inflammatory disease to focus on the conceptual and evidential importance of DAMPs in pathogenesis and why DAMPs represent an entirely new class of targets for clinical translation.
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Affiliation(s)
- R K Boyapati
- MRC Centre for Inflammation Research, Queens Medical Research Institute, Edinburgh, UK.,Gastrointestinal Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK
| | - A G Rossi
- MRC Centre for Inflammation Research, Queens Medical Research Institute, Edinburgh, UK
| | - J Satsangi
- Gastrointestinal Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK
| | - G-T Ho
- MRC Centre for Inflammation Research, Queens Medical Research Institute, Edinburgh, UK.,Gastrointestinal Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK
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Wright EK, Kamm MA, De Cruz P, Hamilton AL, Ritchie KJ, Keenan JI, Leach S, Burgess L, Aitchison A, Gorelik A, Liew D, Day AS, Gearry RB. Comparison of Fecal Inflammatory Markers in Crohn's Disease. Inflamm Bowel Dis 2016; 22:1086-1094. [PMID: 26818420 DOI: 10.1097/mib.0000000000000671] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Fecal biomarkers are used increasingly to monitor Crohn's disease (CD). However, the relative accuracy of different markers in identifying inflammation has been poorly evaluated. We evaluated fecal calprotectin (FC), lactoferrin (FL), and S100A12 (FS) using endoscopic validation in a prospective study of the progression of CD after intestinal resection. METHODS Data were collected from 135 participants in a prospective, randomized, controlled trial aimed at preventing postoperative CD recurrence. Three hundred nineteen stool samples were tested for FC, FL, and FS preoperatively and 6, 12, and 18 months after resection. Colonoscopy was performed at 6 and/or 18 months. Endoscopic recurrence was assessed blindly using the Rutgeerts score. C-reactive protein (CRP) and Crohn's Disease Activity Index (CDAI) were assessed. RESULTS FC, FL, and FS concentrations were elevated preoperatively (median: 1347, 40.9, and 8.4 μg/g, respectively). At 6 months postoperatively, marker concentrations decreased (166, 3.0, 0.9 μg/g) and were higher in recurrent disease than remission (275 versus 72 μg/g, P < 0.001; 5.7 versus 1.6 μg/g, P = 0.007; 2.0 versus 0.8 μg/g, P = 0.188). FC > 135 μg/g, FL > 3.4 μg/g, and FS > 10.5 μg/g indicated endoscopic recurrence (score ≥ i2) with a sensitivity, specificity, and negative predictive value (NPV) of 0.87, 0.66, and 91%; 0.70, 0.68, and 81%; 0.91, 0.12, and 71%, respectively. FC and FL correlated significantly with the presence and severity of endoscopic recurrence, whereas FS, CRP and CDAI did not. CONCLUSIONS FC was the optimal fecal marker for monitoring disease activity in postoperative CD and was superior to CRP and CDAI. FL offered modest sensitivity for detecting recurrent disease, whereas S100A12 was sensitive but had low specificity and NPV.
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Affiliation(s)
- Emily K Wright
- *Department of Gastroenterology, St Vincent's Hospital and University of Melbourne, Melbourne, Australia; †Imperial College London, London, United Kingdom; ‡Department of Surgery, University of Otago, Christchurch, New Zealand; §School of Women's and Children's Health, University of NSW, Sydney, Australia; ‖Department of Paediatrics, University of Otago, Christchurch, New Zealand; ¶Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Australia; and **Department of Medicine, University of Otago, Christchurch, New Zealand
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Abstract
AIM: To determine serum levels of S100A12 in patients with ulcerative colitis (UC) and to explore its potential role in the diagnosis of UC and evaluation of disease development.
METHODS: Serum samples were collected from 66 patients with active UC (A-UC), 24 patients with UC in remission (R-UC) and 20 healthy controls. S100A12 levels were determined by ELISA. The role of S100A12 in the diagnosis and evaluation of disease development was then investigated.
RESULTS: The levels of serum S100A12 were significantly higher in patients with A-UC (725.6 pg/mL ± 239.6 pg/mL) compared with R-UC patients (311.2 pg/mL ± 87.5 pg/mL) and healthy controls (218.6 pg/mL ± 76.8 pg/mL) (P < 0.001). S100A12 was found to be markedly increased in severe UC patients compared with mild and moderate UC patients (P < 0.05). S100A12 was positively correlated with serum C-reactive protein (CRP) in UC patients. Moreover, S100A12 was found to be markedly decreased in UC patients after receiving effective treatment compared with that before treatment (P< 0.05).
CONCLUSION: S100A12 is markedly increased in the sera of UC patients. It can be used to diagnose the disease and predict the disease progression, suggesting that S100A12 is a useful marker for the prediction of UC.
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Heilmann RM, Volkmann M, Otoni CC, Grützner N, Kohn B, Jergens AE, Steiner JM. Fecal S100A12 concentration predicts a lack of response to treatment in dogs affected with chronic enteropathy. Vet J 2016; 215:96-100. [PMID: 27017054 DOI: 10.1016/j.tvjl.2016.03.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Revised: 02/24/2016] [Accepted: 03/01/2016] [Indexed: 12/31/2022]
Abstract
S100A12 is a potential biomarker of gastrointestinal inflammation in dogs and fecal S100A12 concentrations are correlated with disease severity and outcome. The aim of the present study was to investigate whether there was any association between pre-treatment fecal S100A12 concentrations in dogs affected with chronic enteropathy (CE) and the response to treatment. Dogs affected with CE were recruited into the study and were classified as antibiotic-responsive diarrhea (ARD; n = 9), food-responsive diarrhea (FRD; n = 30) or idiopathic inflammatory bowel disease (IBD; n = 25). They were also grouped based on their response to treatment as complete remission (n = 35), partial response (n = 25) or no response (n = 4). Fecal S100A12 concentrations, measured by ELISA, were elevated in dogs affected with IBD compared with those from dogs affected with FRD (P = 0.010) or ARD (P = 0.025). Dogs with IBD that did not respond to treatment (n = 4) had significantly greater fecal S100A12 concentrations than dogs in complete remission (P = 0.009). Measurement of fecal S100A12 at the time of diagnosis discriminated between dogs with IBD that were refractory to therapy (≥2700 ng/g fecal S100A12) from those with at least a partial response (<2700 ng/g fecal S100A12), with a sensitivity of 100% and a specificity of 76%. These preliminary results suggest that testing of fecal S100A12 may be useful for predicting the lack of response to treatment in dogs affected with CE. The utility of serial fecal S100A12 measurements for monitoring dogs undergoing treatment for CE warrants further investigation.
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Affiliation(s)
- Romy M Heilmann
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4474, USA.
| | - Maria Volkmann
- Clinic for Small Animals, Department of Veterinary Medicine, Freie Universität of Berlin, DE-14163 Berlin, Germany
| | - Cristiane C Otoni
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA
| | - Niels Grützner
- Farm Animal Clinic, Department of Clinical Veterinary Medicine, Vetsuisse Faculty Bern, CH-3012 Bern, Switzerland
| | - Barbara Kohn
- Clinic for Small Animals, Department of Veterinary Medicine, Freie Universität of Berlin, DE-14163 Berlin, Germany
| | - Albert E Jergens
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA
| | - Jörg M Steiner
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4474, USA
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50
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Liverani E, Scaioli E, Digby RJ, Bellanova M, Belluzzi A. How to predict clinical relapse in inflammatory bowel disease patients. World J Gastroenterol 2016; 22:1017-1033. [PMID: 26811644 PMCID: PMC4716017 DOI: 10.3748/wjg.v22.i3.1017] [Citation(s) in RCA: 100] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2015] [Revised: 07/07/2015] [Accepted: 11/09/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohn’s disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse.
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