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Zhang Z, Wang HM, Xu ZX, Luan WY, Lin SX, Miao YD. Application of single-cell sequencing in the study of immune cell infiltration in inflammatory bowel disease and colorectal cancer. World J Gastrointest Oncol 2025; 17:107382. [DOI: 10.4251/wjgo.v17.i6.107382] [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] [Received: 03/21/2025] [Revised: 04/14/2025] [Accepted: 05/07/2025] [Indexed: 06/13/2025] Open
Abstract
The rapid advancement of single-cell sequencing (SCS) technology has provided new insights into the relationship between inflammatory bowel disease (IBD) and colorectal cancer (CRC). This technique allows for detailed cellular analysis, enabling researchers to uncover the infiltration patterns of immune cells within the gut microenvironment and their roles in disease progression. This review summarizes significant research findings on the interplay between IBD and CRC, the characteristics of immune cell infiltration, and potential therapeutic targets identified through SCS. The aim is to offer references for future clinical studies and treatment strategies in this field.
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Affiliation(s)
- Zheng Zhang
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The Second Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
- Research and Translational Center for Immunological Disorders, Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Hui-Min Wang
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The Second Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Zhen-Xi Xu
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The Second Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
- Research and Translational Center for Immunological Disorders, Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Wen-Yu Luan
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The Second Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
- Research and Translational Center for Immunological Disorders, Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Si-Xiang Lin
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The Second Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
- Research and Translational Center for Immunological Disorders, Binzhou Medical University, Yantai 264100, Shandong Province, China
| | - Yan-Dong Miao
- Cancer Center, Yantai Affiliated Hospital of Binzhou Medical University, The Second Medical College of Binzhou Medical University, Yantai 264100, Shandong Province, China
- Research and Translational Center for Immunological Disorders, Binzhou Medical University, Yantai 264100, Shandong Province, China
- Guangdong Provincial Key Laboratory of Medical Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, Guangdong Province, China
- Department of Oncology, Xinhui District People’s Hospital, Jiangmen 529100, Guangdong Province, China
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Sassun R, Roufael F, Crippa J, Magistro C, Bertoglio C, Achilli P, Dinuzzi VP, Montroni I, Maggioni D, Spinelli A, Costanzi A, Siracusa C, Dominici R, Leoni V, Larson DW, Mari G, Advanced International Mini‐invasive Surgery Academy Clinical Research Network. Impact of elective surgery on tumor necrosis factor-α, interleukin-6 and quality of life in uncomplicated diverticular disease. Colorectal Dis 2025; 27:e70132. [PMID: 40491034 DOI: 10.1111/codi.70132] [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: 12/03/2024] [Revised: 03/23/2025] [Accepted: 04/07/2025] [Indexed: 06/11/2025]
Abstract
AIM Growing evidence suggests that immune/inflammatory pathways play a crucial role in the persistence of symptoms in diverticular disease (DD). We hypothesize that chronic diverticulitis triggers a self-sustained inflammatory status which can be detected by measuring the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The aim of this study was to investigate the systemic levels of TNF-α and IL-6 before and after elective surgery in patients with DD, and their relationship with the gastrointestinal quality of life index (GIQLI) score. METHOD This prospective multicentric study enrolled patients from the Diverticular Disease Registry (DDR-Trial, NCT04907383). All adult patients diagnosed with symptomatic uncomplicated diverticular disease (SUDD), uncomplicated recurrent diverticulitis (URD) and smouldering diverticulitis (SmD) between 1st December 2022 and 31st December 2023 were included in this study. Exclusion criteria were as follows: no surgery, a concurrent chronic immunomodulated systemic disease, a SARS-CoV-2-positive test in the previous 12 months, a history of cancer in the previous 5 years, patients treated with immunomodulators, an American Society of Anesthesiologists category of class IV, and complicated acute diverticulitis. RESULTS Seventy-two patients were included: 52 (72%) with URD, 11 (15%) with SUDD, and nine (13%) with SmD. The median postsurgery - presurgery (Δ)IL-6 and ΔTNF-α levels were -16.8 and -17.3 pg/mL, respectively (p < 0.001 for both; Wilcoxon test). Spearman correlation revealed a significant, negative association between the ΔGIQLI and the ΔIL-6, as well as the ΔTNF-α (p < 0.001 for both). Greater reduction in the levels of IL-6 and TNF-α following surgery are associated with higher GIQLI scores postoperatively. CONCLUSION Patients with chronic diverticulitis may experience persistent systemic inflammation driven by a colonic trigger. Surgical removal of this trigger appears to enhance GIQLI outcomes reducing IL-6 and TNF-α across surgery.
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Affiliation(s)
- Richard Sassun
- General Surgery Residency Program, University of Milan, Milan, Italy
- General Surgery Unit, Pio XI Hospital, ASST Brianza, Desio, Monza, Italy
| | - Francesca Roufael
- General Surgery Residency Program, University of Milan, Milan, Italy
- General Surgery Unit, Pio XI Hospital, ASST Brianza, Desio, Monza, Italy
| | - Jacopo Crippa
- General Surgery Unit, Vizzolo-Predabissi, ASST Melegnano Martesana, Milan, Italy
| | - Carmelo Magistro
- General Surgery Unit, Vizzolo-Predabissi, ASST Melegnano Martesana, Milan, Italy
| | | | - Pietro Achilli
- Department of Mini-Invasive Surgery, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | | | - Isacco Montroni
- General Surgery Unit, Ospedale Santa Maria Delle Croci, Ravenna, Italy
| | - Dario Maggioni
- General Surgery Unit, Pio XI Hospital, ASST Brianza, Desio, Monza, Italy
| | - Antonino Spinelli
- Division of Colon & Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Andrea Costanzi
- General Surgery Unit, Merate Hospital, ASST Lecco, Merate, Italy
| | - Claudia Siracusa
- Laboratory of Clinical Pathology and Toxicology, Hospital Pio XI of Desio, ASST-Brianza, Desio, MB, Italy
| | - Roberto Dominici
- Laboratory of Clinical Pathology and Toxicology, Hospital Pio XI of Desio, ASST-Brianza, Desio, MB, Italy
| | - Valerio Leoni
- Laboratory of Clinical Pathology and Toxicology, Hospital Pio XI of Desio, ASST-Brianza, Desio, MB, Italy
| | - David Wesley Larson
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Giulio Mari
- General Surgery Unit, Pio XI Hospital, ASST Brianza, Desio, Monza, Italy
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Koshiba R, Kakimoto K, Mizuta N, Numa K, Kinoshita N, Nakazawa K, Hirata Y, Miyazaki T, Higuchi K, Nakamura S, Nishikawa H. C-reactive protein-to-lymphocyte ratio is a novel biomarker for predicting the long-term efficacy of ustekinumab treatment in ulcerative colitis. PLoS One 2024; 19:e0305324. [PMID: 39208267 PMCID: PMC11361563 DOI: 10.1371/journal.pone.0305324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 05/28/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND AND AIM Ustekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. Predicting treatment efficacy in advance would be useful for selecting a therapeutic agent. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment. MATERIALS AND METHODS We retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at Osaka Medical and Pharmaceutical University Hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment. RESULTS Of the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. Baseline C-reactive protein-to-lymphocyte ratio values were significantly higher in the non-remission than in the remission group. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6-62.4, p = 0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (odds ratio: 10, confidence interval: 1.78-56.1, p = 0.009) and that at week 8 (odds ratio: 12, confidence interval: 2.16-66.5, p = 0.005) were significantly associated with clinical remission at week 48. CONCLUSIONS The baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment.
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Affiliation(s)
- Ryoji Koshiba
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Kazuki Kakimoto
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Noboru Mizuta
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Keijiro Numa
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Naohiko Kinoshita
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Kei Nakazawa
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Yuki Hirata
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Takako Miyazaki
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Kazuhide Higuchi
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Shiro Nakamura
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Hiroki Nishikawa
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
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Sataranatarajan K, Adhikari S, Nguyen N, Narasimhan M, Balani J, Muthukumar A. Performance Evaluation of Open Channel Buhlmann Fecal Calprotectin Turbo Assay on Abbott Alinity C Analyzer. Diagnostics (Basel) 2024; 14:1744. [PMID: 39202232 PMCID: PMC11353904 DOI: 10.3390/diagnostics14161744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 07/28/2024] [Accepted: 08/06/2024] [Indexed: 09/03/2024] Open
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal (GI) tract. Fecal calprotectin (fCAL) is a noninvasive laboratory test used in the diagnosis and monitoring of IBDs such as Crohn's disease and ulcerative colitis. The fCAL send-out test that our facility has been offering so far uses an ELISA-based method. In the current study, we sought to validate the performance of a Buhlmann fCAL turbo assay in an automated Abbott Alinity C analyzer (AFCAL) in our core laboratory. Five-day imprecision studies showed good performance for both within-run (5.3%) and between-day (2.5%) measurements. The reportable range was verified as 30-20,000 µg/g. Deming regression and Bland-Altman analysis indicated a strong correlation of r = 0.99 with a low, acceptable bias of 1.8% for AFCAL relative to the predicate Buhlmann fCAL ELISA results. AFCAL's clinical performance was determined retrospectively in 62 patients with ICD codes for IBD. Overall, the implementation of AFCAL in our routine clinical testing has improved our turnaround time, reduced the cost per test, and significantly increased our clinician satisfaction.
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Affiliation(s)
| | - Shishir Adhikari
- Core Laboratory, Clements University Hospital, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; (S.A.); (N.N.)
| | - Ngoc Nguyen
- Core Laboratory, Clements University Hospital, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; (S.A.); (N.N.)
| | - Madhusudhanan Narasimhan
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; (K.S.); (M.N.); (J.B.)
| | - Jyoti Balani
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; (K.S.); (M.N.); (J.B.)
| | - Alagarraju Muthukumar
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; (K.S.); (M.N.); (J.B.)
- Core Laboratory, Clements University Hospital, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; (S.A.); (N.N.)
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Bahaa A, Elbaz T, Elmakhzangy H, Shehata M, Abd El-Kareem D, Gaber A, Hashem MB, El Raziky M. Assessment of IBD disease activity by Interleukin-6 and serum amyloid A in relation with fecal calprotectin and endoscopic indices. Arab J Gastroenterol 2024; 25:299-305. [PMID: 39039004 DOI: 10.1016/j.ajg.2024.07.003] [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: 03/14/2024] [Accepted: 07/05/2024] [Indexed: 07/24/2024]
Abstract
BACKGROUND AND STUDY AIMS Close monitoring of disease activity in IBD patients is essential to avoid long term complications. Although endoscopic assessment is the ideal monitoring tool, the usage of noninvasive biomarkers is more practical and patient friendly. We aimed to study the performance of Interleukin-6(IL-6) and Serum Amyloid A(SAA) as serum biomarkers in assessment of the disease activity of IBD patients in correlation to C-reactive protein (CRP), Fecal Calprotectin (FC) and endoscopic indices. METHODS 83 IBD (26 CD and 57 UC) patients on stable treatment regimen were recruited. Serum markers included CRP, CBC, IL-6, SAA were analyzed, together with FC. These markers were compared with the endoscopic and clinical disease parameters. Harvey-Bradshaw Index (HBI) and the Simple Clinical Colitis Activity Index (SCCAI) were used to assess clinical activity in CD and UC patients, respectively. Endoscopic activity was recorded using the Simple Endoscopic Score (SES) for Crohn's disease or the Mayo Endoscopic Score (MES) for ulcerative colitis. RESULTS In prediction of disease activity, IL-6, SAA and CRP demonstrated good area under receiver operating characteristics (AUC) (>0.7), with FC being the best (0.94) for endoscopically active disease (P < 0.01). Combining FC and IL-6 or SAA improved its discriminative accuracy with an AUC (∼0.96). CONCLUSIONS FC most accurately predicts endoscopic disease activity in IBD patients, in comparison to other studied serological biomarkers. The serum IL-6 and SAA are potential predictors of endoscopic disease activity, and they might be valuable for assessment of disease activity. Finally, a composite score of FC and SAA or IL-6 can increased its diagnostic accuracy.
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Affiliation(s)
- Ahmed Bahaa
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt; Integrated Clinical and Research Centre for Intestinal Disorders (ICRID), Faculty of Medicine, Cairo University, Egypt
| | - Tamer Elbaz
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt; Integrated Clinical and Research Centre for Intestinal Disorders (ICRID), Faculty of Medicine, Cairo University, Egypt
| | - Hesham Elmakhzangy
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt
| | - Mohammed Shehata
- Chemical Pathology Department, Faculty of Medicine, Cairo University, Egypt
| | | | - AbdelAziz Gaber
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt; Integrated Clinical and Research Centre for Intestinal Disorders (ICRID), Faculty of Medicine, Cairo University, Egypt
| | - Mohamed B Hashem
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt; Integrated Clinical and Research Centre for Intestinal Disorders (ICRID), Faculty of Medicine, Cairo University, Egypt
| | - Maissa El Raziky
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Egypt
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Mestrovic A, Perkovic N, Bozic D, Kumric M, Vilovic M, Bozic J. Precision Medicine in Inflammatory Bowel Disease: A Spotlight on Emerging Molecular Biomarkers. Biomedicines 2024; 12:1520. [PMID: 39062093 PMCID: PMC11274502 DOI: 10.3390/biomedicines12071520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/30/2024] [Accepted: 07/06/2024] [Indexed: 07/28/2024] Open
Abstract
Inflammatory bowel diseases (IBD) remain challenging in terms of understanding their causes and in terms of diagnosing, treating, and monitoring patients. Modern diagnosis combines biomarkers, imaging, and endoscopic methods. Common biomarkers like CRP and fecal calprotectin, while invaluable tools, have limitations and are not entirely specific to IBD. The limitations of existing markers and the invasiveness of endoscopic procedures highlight the need to discover and implement new markers. With an ideal biomarker, we could predict the risk of disease development, as well as the possibility of response to a particular therapy, which would be significant in elucidating the pathogenesis of the disease. Recent research in the fields of machine learning, proteomics, epigenetics, and gut microbiota provides further insight into the pathogenesis of the disease and is also revealing new biomarkers. New markers, such as BAFF, PGE-MUM, oncostatin M, microRNA panels, αvβ6 antibody, and S100A12 from stool, are increasingly being identified, with αvβ6 antibody and oncostatin M being potentially close to being presented into clinical practice. However, the specificity of certain markers still remains problematic. Furthermore, the use of expensive and less accessible technology for detecting new markers, such as microRNAs, represents a limitation for widespread use in clinical practice. Nevertheless, the need for non-invasive, comprehensive markers is becoming increasingly important regarding the complexity of treatment and overall management of IBD.
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Affiliation(s)
- Antonio Mestrovic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Nikola Perkovic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Dorotea Bozic
- Department of Gastroenterology, University Hospital of Split, Spinciceva 2, 21000 Split, Croatia; (A.M.); (N.P.); (D.B.)
| | - Marko Kumric
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Marino Vilovic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
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Xin R. Inflammatory Gene Panel Guiding the Study of Genetics in Inflammatory Bowel Disease. Mol Diagn Ther 2024; 28:389-401. [PMID: 38635139 DOI: 10.1007/s40291-024-00709-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/02/2024] [Indexed: 04/19/2024]
Abstract
Inflammatory bowel disease (IBD) is a complex disease that develops through a sequence of molecular events that are still poorly defined. This process is driven by a multitude of context-dependent genes that play different roles based on their environment. The complexity and multi-faceted nature of these genes make it difficult to study the genetic basis of IBD. The goal of this article is to review the key genes in the pathophysiology of IBD and highlight new technology that can be used in further research. This paper examines Nanostring RNA probe technology, which uses tissue analyzed without the use of enzymes, transcription, or amplification. Nanostring offers several panels of genes to test, including an inflammation panel of 234 genes. This article analyzes this panel and reviews the literature for each gene's effect in IBD for use as a framework to review the pathophysiology of the disease. The panel was narrowed to 26 genes with significant evidence of mechanistic potential in IBD, which were then categorized into specific areas of pathogenesis. These include gut barrier breakdown, inappropriate recognition of commensal bacteria, immune cell activation, proinflammatory cytokine release, and subsequent impairment of the anti-inflammatory response. The eventual goal of this paper is the creation of a customized panel of IBD genes that can be used to better understand the genetic mechanism of IBD and aid in the development of future therapies in IBD.
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Affiliation(s)
- Ryan Xin
- Columbia University Irving Medical Center, 177 Fort Washington Avenue, New York, NY, 10032, USA.
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Sarb OF, Sarb AD, Iacobescu M, Vlad IM, Milaciu MV, Ciurmarnean L, Vacaras V, Tantau AI. From Gut to Brain: Uncovering Potential Serum Biomarkers Connecting Inflammatory Bowel Diseases to Neurodegenerative Diseases. Int J Mol Sci 2024; 25:5676. [PMID: 38891863 PMCID: PMC11171869 DOI: 10.3390/ijms25115676] [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: 03/29/2024] [Revised: 05/12/2024] [Accepted: 05/18/2024] [Indexed: 06/21/2024] Open
Abstract
Inflammatory bowel diseases (IBDs) are characterized by chronic gastrointestinal inflammation due to abnormal immune responses to gut microflora. The gut-brain axis is disrupted in IBDs, leading to neurobiological imbalances and affective symptoms. Systemic inflammation in IBDs affects the brain's inflammatory response system, hormonal axis, and blood-brain barrier integrity, influencing the gut microbiota. This review aims to explore the association between dysregulations in the gut-brain axis, serum biomarkers, and the development of cognitive disorders. Studies suggest a potential association between IBDs and the development of neurodegeneration. The mechanisms include systemic inflammation, nutritional deficiency, GBA dysfunction, and the effect of genetics and comorbidities. The objective is to identify potential correlations and propose future research directions to understand the impact of altered microbiomes and intestinal barrier functions on neurodegeneration. Serum levels of vitamins, inflammatory and neuronal damage biomarkers, and neuronal growth factors have been investigated for their potential to predict the development of neurodegenerative diseases, but current results are inconclusive and require more studies.
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Affiliation(s)
- Oliviu-Florentiu Sarb
- Department of Neuroscience, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (O.-F.S.); (I.-M.V.)
- Department of Internal Medicine, 4th Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (M.-V.M.); (L.C.); (A.-I.T.)
| | - Adriana-Daniela Sarb
- Department of Internal Medicine, Heart Institute, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Maria Iacobescu
- Department of Proteomics and Metabolomics, MEDFUTURE Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Irina-Maria Vlad
- Department of Neuroscience, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (O.-F.S.); (I.-M.V.)
| | - Mircea-Vasile Milaciu
- Department of Internal Medicine, 4th Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (M.-V.M.); (L.C.); (A.-I.T.)
| | - Lorena Ciurmarnean
- Department of Internal Medicine, 4th Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (M.-V.M.); (L.C.); (A.-I.T.)
| | - Vitalie Vacaras
- Department of Neuroscience, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (O.-F.S.); (I.-M.V.)
| | - Alina-Ioana Tantau
- Department of Internal Medicine, 4th Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (M.-V.M.); (L.C.); (A.-I.T.)
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Wang P, Qian X, Jiang W, Wang H, Wang Y, Zhou Y, Zhang Y, Huang Y, Zhai X. Cord Blood Transplantation for Very Early-Onset Inflammatory Bowel Disease Caused by Interleukin-10 Receptor Deficiency. J Clin Immunol 2024; 44:67. [PMID: 38372823 DOI: 10.1007/s10875-024-01669-x] [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: 11/06/2023] [Accepted: 02/06/2024] [Indexed: 02/20/2024]
Abstract
PURPOSE Interleukin-10 receptor (IL-10R) deficiency can result in life-threatening very early-onset inflammatory bowel disease (VEO-IBD). Umbilical cord blood transplantation (UCBT) is a curative therapy for patients with IL-10R deficiency. This study aimed to investigate the efficacy of UCBT in treating IL-10R deficiency and develop a predictive model based on pre-transplant factors. METHODS Eighty patients with IL-10R deficiency who underwent UCBT between July 2015 and April 2023 were retrospectively analyzed. Cox proportional hazards regression and random survival forest were used to develop a predictive model. RESULTS Median age at transplant was 13.0 months (interquartile range [IQR], 8.8-25.3 months). With a median follow-up time of 29.4 months (IQR, 3.2-57.1 months), the overall survival (OS) rate was 65.0% (95% confidence interval [CI], 55.3%-76.3%). The engraftment rate was 85% (95% CI, 77%-93%). The cumulative incidences of acute and chronic graft-versus-host disease were 48.2% (95% CI, 37.1%-59.4%) and 12.2% (95% CI, 4.7%-19.8%), respectively. VEO-IBD-associated clinical symptoms were resolved in all survivors. The multivariate analysis showed that IL-6 and stool occult blood were independent prognostic risk factors. The multivariate Cox proportional hazards regression model with stool occult blood, length- or height-for-age Z-score, medical history of sepsis, and cord blood total nucleated cells showed good discrimination ability, with a bootstrap concordance index of 0.767-0.775 in predicting OS. CONCLUSION Better inflammation control before transplantation and higher cord blood total nucleated cell levels can improve patient prognosis. The nomogram can successfully predict OS in patients with IL-10R deficiency undergoing UCBT.
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Affiliation(s)
- Ping Wang
- Department of Hematology/Oncology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
| | - Xiaowen Qian
- Department of Hematology/Oncology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
| | - Wenjin Jiang
- Department of Hematology/Oncology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
| | - Hongsheng Wang
- Department of Hematology/Oncology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
| | - Yuhuan Wang
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
| | - Ying Zhou
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
| | - Ye Zhang
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
| | - Ying Huang
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China
| | - Xiaowen Zhai
- Department of Hematology/Oncology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China.
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Irwin S, Chupina Estrada A, Nelson B, Bullock A, Limketkai B, Ho W, Acton S, Chesnel L, Koon HW. ADS024, a single-strain live biotherapeutic product of Bacillus velezensis alleviates dextran sulfate-mediated colitis in mice, protects human colonic epithelial cells against apoptosis, and maintains epithelial barrier function. Front Microbiol 2024; 14:1284083. [PMID: 38268707 PMCID: PMC10806143 DOI: 10.3389/fmicb.2023.1284083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 12/11/2023] [Indexed: 01/26/2024] Open
Abstract
Epithelial cell apoptosis and compromised gut barrier function are features of inflammatory bowel disease. ADS024 is a single-strain live biotherapeutic product (LBP) of Bacillus velezensis under development for treating ulcerative colitis (UC). The cytoprotective effects of the sterile filtrate of ADS024's secreted products on UC patient-derived colonic tissues, human primary colonic epithelial cells (HPEC), and human colonic epithelial T84 cells were evaluated. ADS024 filtrate significantly inhibited apoptosis and inflammation with reduced Bcl-2 Associated X-protein (BAX) and tumor necrosis factor (TNF) mRNA expression in fresh colonic explants from UC patients. Exposure to UC patient-derived serum exosomes (UCSE) induced apoptosis with increased cleaved caspase 3 protein expression in HPECs. ADS024 filtrate diminished the UCSE-mediated apoptosis by inhibiting cleaved caspase 3. TNFα and interferon-gamma (IFNγ) damaged epithelial barrier integrity with reduced transepithelial electrical resistance (TEER). ADS024 filtrate partially attenuated the TEER reduction and restored tight junction protein 1 (TJP1) expression. Oral live ADS024 treatment reduced weight loss, disease activity, colonic mucosal injury, and colonic expression of interleukin 6 (IL-6) and TNFα in dextran sodium sulfate (DSS)-treated mice with colitis. Thus, ADS024 may protect the colonic epithelial barrier in UC via anti-inflammatory, anti-apoptotic, and tight-junction protection mechanisms.
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Affiliation(s)
- Sophie Irwin
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, United States
| | - Andrea Chupina Estrada
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, United States
| | - Becca Nelson
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, United States
| | - Ashlen Bullock
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, United States
| | - Berkeley Limketkai
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, United States
| | - Wendy Ho
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, United States
| | - Susan Acton
- Adiso Therapeutics Inc., Concord, MA, United States
| | | | - Hon Wai Koon
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, United States
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11
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Nystuen KL, McNamee SM, Akula M, Holton KM, DeAngelis MM, Haider NB. Alzheimer's Disease: Models and Molecular Mechanisms Informing Disease and Treatments. Bioengineering (Basel) 2024; 11:45. [PMID: 38247923 PMCID: PMC10813760 DOI: 10.3390/bioengineering11010045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/15/2023] [Accepted: 12/22/2023] [Indexed: 01/23/2024] Open
Abstract
Alzheimer's Disease (AD) is a complex neurodegenerative disease resulting in progressive loss of memory, language and motor abilities caused by cortical and hippocampal degeneration. This review captures the landscape of understanding of AD pathology, diagnostics, and current therapies. Two major mechanisms direct AD pathology: (1) accumulation of amyloid β (Aβ) plaque and (2) tau-derived neurofibrillary tangles (NFT). The most common variants in the Aβ pathway in APP, PSEN1, and PSEN2 are largely responsible for early-onset AD (EOAD), while MAPT, APOE, TREM2 and ABCA7 have a modifying effect on late-onset AD (LOAD). More recent studies implicate chaperone proteins and Aβ degrading proteins in AD. Several tests, such as cognitive function, brain imaging, and cerebral spinal fluid (CSF) and blood tests, are used for AD diagnosis. Additionally, several biomarkers seem to have a unique AD specific combination of expression and could potentially be used in improved, less invasive diagnostics. In addition to genetic perturbations, environmental influences, such as altered gut microbiome signatures, affect AD. Effective AD treatments have been challenging to develop. Currently, there are several FDA approved drugs (cholinesterase inhibitors, Aß-targeting antibodies and an NMDA antagonist) that could mitigate AD rate of decline and symptoms of distress.
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Affiliation(s)
- Kaden L. Nystuen
- Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, MA 01003, USA
| | - Shannon M. McNamee
- Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
| | - Monica Akula
- Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
| | - Kristina M. Holton
- Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA
- Harvard Stem Cell Institute, Cambridge, MA 02138, USA
- Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Margaret M. DeAngelis
- Department of Ophthalmology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA
| | - Neena B. Haider
- Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
- Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
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12
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Tatsumi Y, Kakimoto K, Hara A, Mizuta N, Numa K, Kinoshita N, Nakazawa K, Koshiba R, Hirata Y, Ota K, Miyazaki T, Nakamura S, Sakagami K, Arimitsu S, Ito H, Nishikawa H. Biomarkers for Monitoring of Changes in Disease Activity in Ulcerative Colitis. J Clin Med 2023; 12:7165. [PMID: 38002777 PMCID: PMC10672609 DOI: 10.3390/jcm12227165] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 11/01/2023] [Accepted: 11/07/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND In recent years, various biomarkers of ulcerative colitis (UC) have emerged; however, few studies have simultaneously examined the utility of multiple biomarkers for monitoring disease activity. Additionally, serum leucine-rich alpha-2 glycoprotein (LRG), a new biomarker, may show a blunt response to anti-TNF antibody therapy. This prospective study explored effective biomarkers that could monitor disease activity changes in patients with UC. In addition, we examined the effect of anti-TNF antibody therapy on changes in LRG. METHODS Blood and stool samples were collected twice from patients with UC: at baseline and at least 8 weeks later. Changes in serum LRG, interleukin (IL)-6, prealbumin (pre-Alb), high-sensitivity C-reactive protein (hs-CRP), CRP, and fecal calprotectin (FC) were measured and correlated with changes in disease activity. The relationship between anti-TNF antibody therapy and LRG levels was also examined in patients with the same disease activity. RESULTS Forty-eight patients with UC (96 samples) were analyzed. ΔLRG and ΔIL-6 correlated strongly with the change in the partial Mayo (pMayo) score between the two time points (ΔpMayo) (r = 0.686, 0.635, respectively). In contrast, FC and IL-6 were particularly accurate predictors of clinical remission, and their area under the curves (AUCs) were significantly higher than that of CRP (AUC: 0.81, 0.76 vs. 0.50; p = 0.001, 0.005). No association was found between the administration of anti-TNF antibody preparations and the LRG values. CONCLUSIONS Correlations were found between changes in UC disease activity and LRG, IL-6, pre-Alb, hs-CRP, CRP, and FC. LRG reflects disease activity during anti-TNF antibody therapy.
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Affiliation(s)
- Yoshihiro Tatsumi
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
| | - Kazuki Kakimoto
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
- Kinshukai Infusion Clinic, Osaka-shi 530-0011, Japan; (K.S.); (S.A.); (H.I.)
| | - Azusa Hara
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
- Kinshukai Infusion Clinic, Osaka-shi 530-0011, Japan; (K.S.); (S.A.); (H.I.)
| | - Noboru Mizuta
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
| | - Keijiro Numa
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
| | - Naohiko Kinoshita
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
| | - Kei Nakazawa
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
| | - Ryoji Koshiba
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
| | - Yuki Hirata
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
- Kinshukai Infusion Clinic, Osaka-shi 530-0011, Japan; (K.S.); (S.A.); (H.I.)
| | - Kazuhiro Ota
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
| | - Takako Miyazaki
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
- Kinshukai Infusion Clinic, Osaka-shi 530-0011, Japan; (K.S.); (S.A.); (H.I.)
| | - Shiro Nakamura
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
| | - Kayoko Sakagami
- Kinshukai Infusion Clinic, Osaka-shi 530-0011, Japan; (K.S.); (S.A.); (H.I.)
| | - Shoko Arimitsu
- Kinshukai Infusion Clinic, Osaka-shi 530-0011, Japan; (K.S.); (S.A.); (H.I.)
| | - Hiroaki Ito
- Kinshukai Infusion Clinic, Osaka-shi 530-0011, Japan; (K.S.); (S.A.); (H.I.)
| | - Hiroki Nishikawa
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki City 569-8686, Japan; (Y.T.); (A.H.); (N.M.); (K.N.); (N.K.); (K.N.); (R.K.); (Y.H.); (K.O.); (T.M.); (S.N.); (H.N.)
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Abdel Hamed EF, Mostafa NE, Farag SM, Ibrahim MN, Ibrahim BH, Rashed HE, Radwan M, Mohamed SY, El Hendawy R, Fawzy EM. Human protozoa infection and dysplasia in ulcerative colitis: a neglected aspect in a prominent disease. Parasitol Res 2023; 122:2709-2718. [PMID: 37710023 PMCID: PMC10567919 DOI: 10.1007/s00436-023-07972-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 09/06/2023] [Indexed: 09/16/2023]
Abstract
The chance of getting colorectal cancer (CRC) is higher in people with chronic ulcerative colitis (UC). The impact of parasitic infections on UC is underappreciated. The purpose of this study was to look into the effect of intestinal protozoal infections on the dysplastic changes generated by UC. The research included 152 adult patients with histologically confirmed UC and 152 healthy controls. Fecal samples were examined for the presence of parasites and fecal calprotectin (FC). The enzyme-linked immunosorbent assay measured serum anti-p53 antibodies (p53Abs) and metallothioneins (MTs). The advanced oxidation protein products (AOPPs) and reduced glutathione (GSH) levels were measured by a spectrophotometric method in all subjects. Serum C-reactive protein (CRP) and IL-6 were also measured. In addition, histopathological and immunohistochemical investigations of intestinal tissue were done. Our results exhibited significant increases in FC and CRP, IL-6, AOPPs, MTs, and p53Abs in ulcerative colitis patients with parasitic infections compared to those without parasites. In contrast, GSH levels showed a significant decrease in the same group compared with other groups. Histopathological and immunohistochemical assessments of intestinal tissue signified severe inflammation and strong expression of PD-L1 in patients with parasitic infections compared to others without parasitic infections. Our research indicated a greater frequency of intestinal protozoa in UC patients with elevated inflammatory and dysplastic biomarker levels. This suggests that these parasites may be involved in the etiology of chronic UC and the associated carcinogenetic process. This is the first report of a link between parasitic infections and dysplastic alterations in UC patients.
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Affiliation(s)
- Enas F Abdel Hamed
- Department of Medical Parasitology, Faculty of Medicine, Zagazig University, El Kawmia Square, Zagazig, Sharkia Governorate, Egypt.
| | - Nahed E Mostafa
- Department of Medical Parasitology, Faculty of Medicine, Zagazig University, El Kawmia Square, Zagazig, Sharkia Governorate, Egypt
| | - Shaimaa M Farag
- Department of Medical Parasitology, Faculty of Medicine, Zagazig University, El Kawmia Square, Zagazig, Sharkia Governorate, Egypt
| | - Mohamed N Ibrahim
- Clinical Laboratories Department, College of Applied Medical Sciences, Jouf University, Qurrayat, Kingdom of Saudi Arabia
| | - Basma H Ibrahim
- Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Sharkia, Egypt
| | - Hayam E Rashed
- Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Sharkia, Egypt
| | - Mona Radwan
- Department of Community and Occupational Medicine, Faculty of Medicine, Zagazig University, Zagazig, Sharkia, Egypt
| | - Salem Y Mohamed
- Department of Internal Medicine, Gastroenterology & Hepatology Unit, Zagazig University, Zagazig, Egypt
| | - Ramy El Hendawy
- Department of Tropical Medicine, Zagazig University, Zagazig, Egypt
| | - Eman M Fawzy
- Department of Medical Parasitology, Faculty of Medicine, Zagazig University, El Kawmia Square, Zagazig, Sharkia Governorate, Egypt
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14
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van Stigt AC, Dalm VASH, Nagtzaam NMA, van Hagen PM, Dik WA, IJspeert H. Soluble Interleukin-2 Receptor/White Blood Cell Ratio Reflects Granulomatous Disease Progression in Common Variable Immune Deficiency. J Clin Immunol 2023; 43:1754-1757. [PMID: 37542638 PMCID: PMC10661782 DOI: 10.1007/s10875-023-01560-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 07/21/2023] [Indexed: 08/07/2023]
Affiliation(s)
- Astrid C van Stigt
- Erasmus MC, University Medical Center Rotterdam, Laboratory Medical Immunology, Department of Immunology, Rotterdam, The Netherlands
- Erasmus MC, University Medical Center Rotterdam, Department of Internal Medicine, Division of Allergy & Clinical Immunology, Rotterdam, The Netherlands
- Erasmus MC, University Medical Center Rotterdam, Academic Center for Rare Immunological Diseases (RIDC), Rotterdam, The Netherlands
| | - Virgil A S H Dalm
- Erasmus MC, University Medical Center Rotterdam, Laboratory Medical Immunology, Department of Immunology, Rotterdam, The Netherlands
- Erasmus MC, University Medical Center Rotterdam, Department of Internal Medicine, Division of Allergy & Clinical Immunology, Rotterdam, The Netherlands
- Erasmus MC, University Medical Center Rotterdam, Academic Center for Rare Immunological Diseases (RIDC), Rotterdam, The Netherlands
| | - Nicole M A Nagtzaam
- Erasmus MC, University Medical Center Rotterdam, Laboratory Medical Immunology, Department of Immunology, Rotterdam, The Netherlands
- Erasmus MC, University Medical Center Rotterdam, Academic Center for Rare Immunological Diseases (RIDC), Rotterdam, The Netherlands
| | - P Martin van Hagen
- Erasmus MC, University Medical Center Rotterdam, Laboratory Medical Immunology, Department of Immunology, Rotterdam, The Netherlands
- Erasmus MC, University Medical Center Rotterdam, Department of Internal Medicine, Division of Allergy & Clinical Immunology, Rotterdam, The Netherlands
- Erasmus MC, University Medical Center Rotterdam, Academic Center for Rare Immunological Diseases (RIDC), Rotterdam, The Netherlands
| | - Willem A Dik
- Erasmus MC, University Medical Center Rotterdam, Laboratory Medical Immunology, Department of Immunology, Rotterdam, The Netherlands
- Erasmus MC, University Medical Center Rotterdam, Academic Center for Rare Immunological Diseases (RIDC), Rotterdam, The Netherlands
| | - Hanna IJspeert
- Erasmus MC, University Medical Center Rotterdam, Laboratory Medical Immunology, Department of Immunology, Rotterdam, The Netherlands.
- Erasmus MC, University Medical Center Rotterdam, Academic Center for Rare Immunological Diseases (RIDC), Rotterdam, The Netherlands.
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15
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Feng W, Zhu L, Liu Y, Xu L, Shen H. C-reactive protein/albumin ratio and IL-6 are associated with disease activity in patients with ulcerative colitis. J Clin Lab Anal 2023; 37:e24843. [PMID: 36725336 PMCID: PMC9978084 DOI: 10.1002/jcla.24843] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 01/02/2023] [Accepted: 01/05/2023] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Cytokines are key mediators of the inflammation in ulcerative colitis (UC); there are inconsistent data on cytokines profile in patients with UC. C-reactive protein/albumin ratio (CRP/ALB) has also been found as an inflammatory indicator. However, the role of CRP/ALB in UC remains unclear. We aimed to evaluate the CRP/ALB ratio and cytokines profile in patients with UC. We further explore the association between CRP/ALB and inflammatory markers, such as erythrocyte sedimentation rate (ESR), fecal calprotectin (FC) and cytokines. METHODS One hundred thirty UC patients and 65 controls were included in the study. Clinical and laboratory findings were retrospectively reviewed; differences in variables between two groups were examined using the Mann-Whitney U-test. The association between CRP/ALB, cytokines, and clinical parameters was determined by Spearman's correlation test. RESULTS CRP/ALB levels were significantly elevated in active UC patients. The optimal cutoff level of the CRP/ALB was 0.083. The patients with active UC had a median interleukin-6 (IL-6) level of 7.715 pg/ml (interquartile ranges, IQR 3.475-14.63), which was significantly higher than those in remission (2.95 pg/ml, IQR 2.17-5.44) (p < 0.001). Positive correlations between CRP/ALB and inflammatory markers were also observed. CONCLUSIONS Our results suggest that CRP/ALB and IL-6 could be potential biomarkers for assessment of clinical activity in Chinese patients with UC.
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Affiliation(s)
- Wan Feng
- Department of GastroenterologyAffiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine)NanjingChina
| | - Lei Zhu
- Department of GastroenterologyAffiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine)NanjingChina
| | - Yajun Liu
- Department of GastroenterologyAffiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine)NanjingChina
| | - Luzhou Xu
- Department of GastroenterologyAffiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine)NanjingChina
| | - Hong Shen
- Department of GastroenterologyAffiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine)NanjingChina
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16
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Uspenskiy YP, Ivanov SV, Krasichkov AS, Galagudza MM, Fominykh YA. Relationship between Undernutrition and Anemia in Patients with Ulcerative Colitis. GASTROENTEROLOGY INSIGHTS 2022; 14:27-36. [DOI: 10.3390/gastroent14010003] [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: 01/03/2025] Open
Abstract
This study aimed to assess the relationship between malnutrition and anemia in patients with ulcerative colitis (UC). The cross-sectional retrospective study included 80 patients with UC. Body mass index and total body fat mass were derived retrospectively from bioimpedance measurements. Anemia was diagnosed retrospectively according to WHO criteria. A binary logistic regression was performed to study the relationship between nutritional status parameters and anemia, and adjusted for demographic and disease-associated characteristics. The prevalence of anemia in the study population was 40.0%. Among all included patients, 86.3% had acute disease corresponding to S1–S3 disease behavior. In the adjusted binary logistic model, total serum protein level below 64 g/L and low body fat percentage were associated with high odds for the of development of anemia, with odds ratios of 5.1 (95% CI 1.5; 17.8; p = 0.01) and 8.5 (95% CI 1.1; 63.6; p = 0.037), respectively. The adjusted model included sex, age, disease activity, extent of gut involvement, quantity of relapses from disease onset, and treatment with immunosuppressive drugs as confounders. Hypoproteinemia and low body fat percentage were associated with anemia in patients with UC. These results suggested that undernutrition may be involved as one of the causative factors of anemia in UC.
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Affiliation(s)
- Yury P. Uspenskiy
- Department of Faculty Therapy, Saint Petersburg State Pediatric Medical University, 2 Litovskaya Street, 194100 Saint Petersburg, Russia
- Department of Internal Medicine, Faculty of Dentistry, Pavlov First Saint Petersburg State Medical University, 6–8 Lev Tolstoy Street, 197022 Saint Petersburg, Russia
| | - Sergei V. Ivanov
- Department of Faculty Therapy, Saint Petersburg State Pediatric Medical University, 2 Litovskaya Street, 194100 Saint Petersburg, Russia
- Department of Internal Medicine, Faculty of Dentistry, Pavlov First Saint Petersburg State Medical University, 6–8 Lev Tolstoy Street, 197022 Saint Petersburg, Russia
| | - Alexander S. Krasichkov
- Department of Radio Engineering Systems, Saint Petersburg Electrotechnical University “LETI”, 5 Professor Popov Street, 197376 Saint Petersburg, Russia
| | - Michael M. Galagudza
- Department of Microcirculation and Myocardial Metabolism, Institute of Experimental Medicine, Almazov National Medical Research Centre, 15B Parkhomenko Street, 194021 Saint Petersburg, Russia
- Laboratory of Radio and Optoelectronic Instruments for Bioinformation Technologies for Early Diagnostics of Live System Pathologies, Institute for Analytical Instrumentation, Russian Academy of Sciences, 31–33A Ivan Chernykh Street, 198095 Saint Petersburg, Russia
| | - Yulia A. Fominykh
- Department of Faculty Therapy, Saint Petersburg State Pediatric Medical University, 2 Litovskaya Street, 194100 Saint Petersburg, Russia
- Department of Internal Medicine, Faculty of Dentistry, Pavlov First Saint Petersburg State Medical University, 6–8 Lev Tolstoy Street, 197022 Saint Petersburg, Russia
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17
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Yadav V, House A, Matiz S, McCoubrey LE, Bettano KA, Bhave L, Wang M, Fan P, Zhou S, Woodhouse JD, Poimenidou E, Dou L, Basit AW, Moy LY, Saklatvala R, Hegde LG, Yu H. Ileocolonic-Targeted JAK Inhibitor: A Safer and More Effective Treatment for Inflammatory Bowel Disease. Pharmaceutics 2022; 14:2385. [PMID: 36365202 PMCID: PMC9698010 DOI: 10.3390/pharmaceutics14112385] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 10/29/2022] [Accepted: 11/03/2022] [Indexed: 07/30/2023] Open
Abstract
Janus kinase (JAK) inhibitors, such as tofacitinib (Xeljanz) and filgotinib (Jyseleca), have been approved for treatment of ulcerative colitis with several other JAK inhibitors in late-stage clinical trials for inflammatory bowel disease (IBD). Despite their impressive efficacy, the risk of adverse effects accompanying the use of JAK inhibitors has brought the entire class under scrutiny, leading to them receiving an FDA black box warning. In this study we investigated whether ileocolonic-targeted delivery of a pan-JAK inhibitor, tofacitinib, can lead to increased tissue exposure and reduced systemic exposure compared to untargeted formulations. The stability of tofacitinib in the presence of rat colonic microbiota was first confirmed. Next, in vivo computed tomography imaging was performed in rats to determine the transit time and disintegration site of ileocolonic-targeted capsules compared to gastric release capsules. Pharmacokinetic studies demonstrated that systemic drug exposure was significantly decreased, and colonic tissue exposure increased at 10 mg/kg tofacitinib dosed in ileocolonic-targeted capsules compared to gastric release capsules and an oral solution. Finally, in a rat model of LPS-induced colonic inflammation, targeted tofacitinib capsules significantly reduced concentrations of proinflammatory interleukin 6 in colonic tissue compared to a vehicle-treated control (p = 0.0408), unlike gastric release tofacitinib capsules and orally administered dexamethasone. Overall, these results support further development of ileocolonic-targeted tofacitinib, and potentially other specific JAK inhibitors in pre-clinical and clinical development, for the treatment of IBD.
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Affiliation(s)
- Vipul Yadav
- Intract Pharma Ltd., London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UK
| | - Aileen House
- Merck & Co., Inc., 126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ 07065, USA
| | - Silvia Matiz
- Intract Pharma Ltd., London Bioscience Innovation Centre, 2 Royal College Street, London NW1 0NH, UK
| | - Laura E. McCoubrey
- UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK
| | - Kimberly A. Bettano
- Merck & Co., Inc., 126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ 07065, USA
| | - Leena Bhave
- Merck & Co., Inc., 126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ 07065, USA
| | - Meiyao Wang
- Merck & Co., Inc., 126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ 07065, USA
- Karuna Therapeutics, Inc., 99 High St Floor 26, Boston, MA 02110, USA
| | - Peter Fan
- Merck & Co., Inc., 126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ 07065, USA
- Treeline Biosciences, 500 Arsenal Street, Suite 201, Watertown, MA 02472, USA
| | - Siqun Zhou
- Merck & Co., Inc., 126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ 07065, USA
| | - Janice D. Woodhouse
- Merck & Co., Inc., 126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ 07065, USA
| | | | - Liu Dou
- School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou 510275, China
| | - Abdul W. Basit
- UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK
| | - Lily Y. Moy
- Merck & Co., Inc., 126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ 07065, USA
| | - Robert Saklatvala
- Merck & Co., Inc., 126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ 07065, USA
- Kallyope, 430 East 29th Street, 10th Floor, New York, NY 10016, USA
| | | | - Hongshi Yu
- Merck & Co., Inc., 126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ 07065, USA
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Bamola VD, Dubey D, Samanta P, Kedia S, Ahuja V, Madempudi RS, Neelamraju J, Chaudhry R. Role of a probiotic strain in the modulation of gut microbiota and cytokines in inflammatory bowel disease. Anaerobe 2022; 78:102652. [PMID: 36198385 DOI: 10.1016/j.anaerobe.2022.102652] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 09/24/2022] [Accepted: 09/26/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVE To assess the effect of a probiotic strain Bacillus clausii UBBC-07 on gut microbiota and cytokines in IBD patients. METHOD Patients were randomly allocated to either placebo or probiotic Bacillus clausii UBBC-07 for four weeks along with the standard medical treatment (SMT). Enrolled patients were evaluated before and after intervention for presence of the given probiotic, change in gut microbiota, change in serum cytokines, serotonin and dopamine, symptoms of disease, physical, behavioral and psychological parameters. RESULTS Probiotic strain Bacillus clausii UBBC-07 showed good survival in IBD patients in the treatment group (p < 0.01) without any reported adverse event. Metagenomic analysis showed that the given probiotic strain was able to modulate the gut microbiota in treated group. Phylum Firmicutes was increased and phylum Bacteroidetes was decreased in the probiotic treated group. A significant increase was observed in the abundance of anaerobic bacterial genera Lactobacillus, Bifidobacterium and Faecalibacterium in the probiotic treated group (p < 0.01) as compared to placebo group. Significant increase was observed in IL-10 (p < 0.05) and variable decrease in the secretion of IL-1β, TNF- α, IL-6, IL -17 and IL -23 in probiotic treated group. In the treatment group a significant decrease in the symptoms of IBD and improvement in the psychological parameter to various degrees was noted. CONCLUSION These results indicated that probiotic strain B clausii UBBC-07 affected the gut microbiota and cytokine secretion and shown efficacy in IBD patients.
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Affiliation(s)
- V Deepak Bamola
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Divya Dubey
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Projoyita Samanta
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, 110029, India
| | - Ratna Sudha Madempudi
- Centre for Research & Development, Unique Biotech Ltd., Plot No. 2, Phase-II, Alexandria Knowledge Park, Hyderabad, Telangana, 500078, India
| | - Jayanthi Neelamraju
- Centre for Research & Development, Unique Biotech Ltd., Plot No. 2, Phase-II, Alexandria Knowledge Park, Hyderabad, Telangana, 500078, India
| | - Rama Chaudhry
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, 110029, India.
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Zahirović A, Berlec A. Targeting IL-6 by engineered Lactococcus lactis via surface-displayed affibody. Microb Cell Fact 2022; 21:143. [PMID: 35842694 PMCID: PMC9287920 DOI: 10.1186/s12934-022-01873-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 07/06/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Dysregulated production of interleukin (IL)-6 is implicated in the pathology of inflammatory bowel disease (IBD). Neutralization of IL-6 in the gut by safe probiotic bacteria may help alleviate intestinal inflammation. Here, we developed Lactococcus lactis with potent and selective IL-6 binding activity by displaying IL-6-specific affibody on its surface. RESULTS Anti-IL-6 affibody (designated as ZIL) was expressed in fusion with lactococcal secretion peptide Usp45 and anchoring protein AcmA. A high amount of ZIL fusion protein was detected on bacterial surface, and its functionality was validated by confocal microscopy and flow cytometry. Removal of IL-6 from the surrounding medium by the engineered L. lactis was evaluated using enzyme-linked immunosorbent assay. ZIL-displaying L. lactis sequestered recombinant human IL-6 from the solution in a concentration-dependent manner by up to 99% and showed no binding to other pro-inflammatory cytokines, thus proving to be highly specific for IL-6. The removal was equally efficient across different IL-6 concentrations (150-1200 pg/mL) that were found to be clinically relevant in IBD patients. The ability of engineered bacteria to capture IL-6 from cell culture supernatant was assessed using immunostimulated human monocytic cell lines (THP-1 and U-937) differentiated into macrophage-like cells. ZIL-displaying L. lactis reduced the content of IL-6 in the supernatants of both cell lines in a concentration-dependent manner by up to 94%. Dose response analysis showed that bacterial cell concentrations of 107 and 109 CFU/mL (colony forming units per mL) were required for half-maximal removal of recombinant and macrophage-derived IL-6, respectively. CONCLUSION The ability of ZIL-displaying L. lactis to bind pathological concentrations of IL-6 at common bacterial doses suggests physiological significance.
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Affiliation(s)
- Abida Zahirović
- Department of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia
| | - Aleš Berlec
- Department of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia. .,Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
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20
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Dworzański W, Cholewińska E, Fotschki B, Juśkiewicz J, Ognik K. Oxidative, epigenetic changes and fermentation processes in the intestine of rats fed high-fat diets supplemented with various chromium forms. Sci Rep 2022; 12:9817. [PMID: 35701510 PMCID: PMC9198011 DOI: 10.1038/s41598-022-13328-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Accepted: 05/23/2022] [Indexed: 11/13/2022] Open
Abstract
The aim of the study was to determine how feeding rats a high-fat diet (F) supplemented with various forms of chromium affects the responses of the immune and redox systems, as well as epigenetic changes in the ileal tissue and the course of fermentation processes in the caecum. The rats received a pharmacologically relevant dose 0.3 mg Cr/kg body weight in form of chromium(III) picolinate (Cr-Pic), chromium (III)-methionine (Cr-Met), or chromium nanoparticles (Cr-NPs). The F increased DNA oxidation and raised the level of interleukin IL-6. The F was shown to reduce the intensity of fermentation processes in the caecum while increasing the activity of potentially harmful enzymes in the faeces. The addition of Cr in the form of Cr-NPs and Cr-Met in rats fed F beneficially increased mobilization of enzymes of the DNA repair pathway. All forms of Cr, but especially Cr-NPs, beneficially decreased the activity of caecal bacterial β-glucuronidase, faecal β-glucosidase and β-glucuronidase. However, due to the increase in level of cytokine IL-2 in small intestinal wall, induced by all tested forms of chromium, it is difficult to state conclusively that this element can mitigate unfavourable pro-inflammatory and oxidative changes induced by a F in the small intestinal wall.
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Affiliation(s)
- Wojciech Dworzański
- Chair and Department of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090, Lublin, Poland
| | - Ewelina Cholewińska
- Department of Biochemistry and Toxicology, Faculty of Animal Sciences and Bioeconomy, University of Life Sciences in Lublin, Akademicka 13, 20-950, Lublin, Poland.
| | - Bartosz Fotschki
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland
| | - Jerzy Juśkiewicz
- Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland.
| | - Katarzyna Ognik
- Department of Biochemistry and Toxicology, Faculty of Animal Sciences and Bioeconomy, University of Life Sciences in Lublin, Akademicka 13, 20-950, Lublin, Poland
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21
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Werner MCF, Wirgenes KV, Shadrin AA, Lunding SH, Rødevand L, Hjell G, Ormerod MBEG, Haram M, Agartz I, Djurovic S, Melle I, Aukrust P, Ueland T, Andreassen OA, Steen NE. Limited association between infections, autoimmune disease and genetic risk and immune activation in severe mental disorders. Prog Neuropsychopharmacol Biol Psychiatry 2022; 116:110511. [PMID: 35063598 DOI: 10.1016/j.pnpbp.2022.110511] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 12/23/2021] [Accepted: 01/13/2022] [Indexed: 10/19/2022]
Abstract
BACKGROUND Low-grade inflammation may be part of the underlying mechanism of schizophrenia and bipolar disorder. We investigated if genetic susceptibility, infections or autoimmunity could explain the immune activation. METHODS Seven immune markers were selected based on indicated associations to severe mental disorders (IL-1Ra, sIL-2R, IL-18, sgp130, sTNFR-1, APRIL, ICAM-1) and measured in plasma of patients with schizophrenia (SCZ, N = 732) and bipolar spectrum disorders (BD, N = 460) and healthy controls (HC, N = 938). Information on rate of infections and autoimmune diseases were obtained from Norwegian national health registries for a twelve-year period. Polygenic risk scores (PRS) of SCZ and BD were calculated from genome-wide association studies. Analysis of covariance were used to test effects of infection rate, autoimmune disease and PRS on differences in immune markers between patients and HC. RESULTS Infection rate differed between all groups (BD > HC > SCZ, all p < 0.001) whereas autoimmune disease was more frequent in BD compared to SCZ (p = 0.004) and HC (p = 0.003). sIL-2R was positively associated with autoimmune disease (p = 0.001) and negatively associated with PRS of SCZ (p = 0.006) across SCZ and HC; however, associations represented only small changes in the difference of sIL-2R levels between SCZ and HC. CONCLUSION There were few significant associations between rate of infections, autoimmune disease or PRS and altered immune markers in SCZ and BD, and the detected associations represented only small changes in the immune aberrations. The findings suggest that most of the low-grade inflammation in SCZ and BD is explained by other factors than the underlying PRS, autoimmunity and infection rates.
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Affiliation(s)
- Maren Caroline Frogner Werner
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Katrine Verena Wirgenes
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
| | - Alexey A Shadrin
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Synve Hoffart Lunding
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Linn Rødevand
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Gabriela Hjell
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry, Ostfold Hospital, Graalum, Norway
| | | | - Marit Haram
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Ingrid Agartz
- NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden
| | - Srdjan Djurovic
- Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Ingrid Melle
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Thor Ueland
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen - Thrombosis Research and Expertise Center (TREC), University of Tromsø, Tromsø, Norway
| | - Ole Andreas Andreassen
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Nils Eiel Steen
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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22
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Selective Forms of Therapy in the Treatment of Inflammatory Bowel Diseases. J Clin Med 2022; 11:jcm11040994. [PMID: 35207271 PMCID: PMC8879972 DOI: 10.3390/jcm11040994] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 02/05/2022] [Accepted: 02/08/2022] [Indexed: 12/17/2022] Open
Abstract
Selective interference with the functioning of the immune system consisting of the selective blockade of pro-inflammatory factors is a modern, promising, and developing strategy for the treatment of diseases resulting from dysregulation of the immune system, including inflammatory bowel disease. Inhibition of the TNF alpha pathway, group 12/23 cytokines, and lymphocyte migration is used in the treatment of severe or moderate ulcerative colitis and Crohn’s disease. Intracellular signal transduction by influencing the phosphorylation of SAT (signal transducer and activator of transcription) proteins remains in clinical trials.
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23
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Werner MCF, Wirgenes KV, Shadrin A, Lunding SH, Rødevand L, Hjell G, Ormerod MBEG, Haram M, Agartz I, Djurovic S, Melle I, Aukrust P, Ueland T, Andreassen OA, Steen NE. Immune marker levels in severe mental disorders: associations with polygenic risk scores of related mental phenotypes and psoriasis. Transl Psychiatry 2022; 12:38. [PMID: 35082268 PMCID: PMC8792001 DOI: 10.1038/s41398-022-01811-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 12/22/2021] [Accepted: 01/10/2022] [Indexed: 12/13/2022] Open
Abstract
Several lines of evidence implicate immune abnormalities in the pathophysiology of severe mental disorders (SMD) and comorbid mental disorders. Here, we use the data from genome-wide association studies (GWAS) of autoimmune diseases and mental phenotypes associated with SMD to disentangle genetic susceptibilities of immune abnormalities in SMD. We included 1004 patients with SMD and 947 healthy controls (HC) and measured plasma levels of IL-1Ra, sIL-2R, gp130, sTNFR-1, IL-18, APRIL, and ICAM-1. Polygenic risk scores (PRS) of six autoimmune disorders, CRP, and 10 SMD-related mental phenotypes were calculated from GWAS. General linear models were applied to assess the association of PRS with immune marker abnormalities. We found negative associations between PRS of educational attainment and IL-1Ra (P = 0.01) and IL-18 (P = 0.01). There were nominal positive associations between PRS of psoriasis and sgp130 (P = 0.02) and PRS of anxiety and IL-18 (P = 0.03), and nominal negative associations between PRS of anxiety and sIL-2R (P = 0.02) and PRS of educational attainment and sIL-2R (P = 0.03). Associations explained minor amounts of the immune marker plasma-level difference between SMD and HC. Different PRS and immune marker associations in the SMD group compared to HC were shown for PRS of extraversion and IL-1Ra ([interaction effect (IE), P = 0.002), and nominally for PRS of openness and IL-1Ra (IE, P = 0.02) and sTNFR-1 (IE, P = 0.04). Our findings indicate polygenic susceptibilities to immune abnormalities in SMD involving genetic overlap with SMD-related mental phenotypes and psoriasis. Associations might suggest immune genetic factors of SMD subgroups characterized by autoimmune or specific mental features.
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Affiliation(s)
- Maren Caroline Frogner Werner
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Katrine Verena Wirgenes
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
| | - Alexey Shadrin
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Synve Hoffart Lunding
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Linn Rødevand
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Gabriela Hjell
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Psychiatry, Ostfold Hospital, Graalum, Norway
| | | | - Marit Haram
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Ingrid Agartz
- NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
- Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden
| | - Srdjan Djurovic
- Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
- NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Ingrid Melle
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
- Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Thor Ueland
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
- K.G. Jebsen - Thrombosis Research and Expertise Center (TREC), University of Tromsø, Tromsø, Norway
| | - Ole Andreas Andreassen
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Nils Eiel Steen
- NORMENT, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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24
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Kini A, Zhao B, Basic M, Roy U, Iljazovic A, Odak I, Ye Z, Riederer B, Di Stefano G, Römermann D, Koenecke C, Bleich A, Strowig T, Seidler U. Upregulation of antimicrobial peptide expression in slc26a3-/- mice with colonic dysbiosis and barrier defect. Gut Microbes 2022; 14:2041943. [PMID: 35230892 PMCID: PMC8890434 DOI: 10.1080/19490976.2022.2041943] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 02/09/2022] [Indexed: 02/04/2023] Open
Abstract
Genetic defects in SLC26A3 (DRA), an intestinal Cl-/HCO3- exchanger, result in congenital chloride diarrhea (CLD), marked by lifelong acidic diarrhea and a high risk of inflammatory bowel disease. Slc26a3-/- mice serve as a model to understand the pathophysiology of CLD and search for treatment options. This study investigates the microbiota changes in slc26a3-/- colon, the genotype-related causes for the observed microbiota alterations, its inflammatory potential, as well as the corresponding host responses. The luminal and the mucosa-adherent cecal and colonic microbiota of cohoused slc26a3-/- and wt littermates were analyzed by 16S rRNA gene sequencing. Fecal microbiota transfer from cohoused slc26a3-/- and wt littermates to germ-free wt mice was performed to analyze the stability and the inflammatory potential of the communities.The cecal and colonic luminal and mucosa-adherent microbiota of slc26a3-/- mice was abnormal from an early age, with a loss of diversity, of short-chain fatty acid producers, and an increase of pathobionts. The transfer of slc26a3-/- microbiota did not result in intestinal inflammation and the microbial diversity in the recipient mice normalized over time. A strong increase in the expression of Il22, Reg3β/γ, Relmβ, and other proteins with antimicrobial functions was observed in slc26a3-/- colon from juvenile age, while the mucosal and systemic inflammatory signature was surprisingly mild. The dysbiotic microbiota, low mucosal pH, and mucus barrier defect in slc26a3-/- colon are accompanied by a stark upregulation of the expression of a panel of antimicrobial proteins. This may explain the low inflammatory burden in the gut of these mice.
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Affiliation(s)
| | - Bei Zhao
- Microbial Immune Regulation Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
| | | | - Urmi Roy
- Microbial Immune Regulation Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Aida Iljazovic
- Microbial Immune Regulation Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
| | - Ivan Odak
- Institute of Immunology Hannover Medical School Hannover, Germany
| | | | | | | | | | | | | | - Till Strowig
- Microbial Immune Regulation Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany
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25
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Wong WY, Chan BD, Leung TW, Chen M, Tai WCS. Beneficial and anti-inflammatory effects of formulated prebiotics, probiotics, and synbiotics in normal and acute colitis mice. J Funct Foods 2022. [DOI: 10.1016/j.jff.2021.104871] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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Zhang Y, Ren L, Sun J, Han F, Guo X. Increased Serum Soluble Interleukin-2 Receptor Associated with Severity of Acute Exacerbation of Chronic Obstructive Pulmonary Disease. Int J Chron Obstruct Pulmon Dis 2021; 16:2561-2573. [PMID: 34522094 PMCID: PMC8434832 DOI: 10.2147/copd.s321904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 08/23/2021] [Indexed: 11/23/2022] Open
Abstract
Background This study aimed to reveal the correlation between serum soluble interleukin-2 receptor (sIL-2R) and prognosis in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods A total of 315 patients diagnosed with AECOPD between December 2017 and June 2020 were enrolled. The patients were divided into the good and adverse groups based on the outcomes. An adverse outcome in COPD exacerbation was defined by the presence of at least one of the following: (1) death from a respiratory cause during hospitalisation or within 1 month of follow-up; (2) intensive care unit admission; (3) invasive or non-invasive mechanical ventilation; and (4) COPD-related emergency visit or readmission within 1 month of follow-up. A good outcome was considered as the absence of all the aforementioned issues. The patients underwent lung function (spirometry) assessment, and clinical and inflammatory profiles were collected. Univariate and multivariate analyses were performed to identify the correlation between serum sIL-2R concentration and other variables related to adverse outcomes of AECOPD. The receiver operating characteristic curve was used to show the predictive ability of sIL-2R for adverse outcomes of AECOPD. Results We enrolled 315 patients, of whom 161 and 154 had good and adverse outcomes, respectively. We demonstrated that patients with adverse outcomes of AECOPD had a higher concentration of serum sIL-2R than patients with good outcomes (p < 0.001). The increased serum sIL-2R was positively associated with mMRC scores (p < 0.001), GLOD grades (p < 0.001), frequent exacerbation (p < 0.001), and smoking (p < 0.001) in patients with AECOPD and negatively correlated with pulmonary function (p < 0.001). An elevated sIL-2R level was a predictor for the risk of adverse outcomes in AECOPD with a cut-off value of 860 U/mL. Conclusion Increased serum sIL-2R concentration correlated with the risk of the adverse outcomes in AECOPD, indicating that it can be a predictive factor contributing to the diagnosis and assessment of adverse outcomes in patients with AECOPD.
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Affiliation(s)
- Yue Zhang
- Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People's Republic of China
| | - Lianping Ren
- Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People's Republic of China
| | - Jinyuan Sun
- Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People's Republic of China
| | - Fengfeng Han
- Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People's Republic of China
| | - Xuejun Guo
- Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People's Republic of China
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Yang M, Yin Y, Zhang J, Yi W, Liu J, Chen D, Zhang H, Fan X, Zhang Y, Zhu M, Qin S, Lv Z, Yu F. Cytokines: Application in recurrence appraisal for differentiated thyroid carcinoma and their relation with radioiodine ablation. J Cell Biochem 2021; 122:1350-1359. [PMID: 34143519 DOI: 10.1002/jcb.30016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 04/15/2021] [Accepted: 05/06/2021] [Indexed: 11/09/2022]
Abstract
The limitations in discriminating preablation disease-active status of differentiated thyroid carcinoma (DTC) still represent a major challenge to radioiodine dose management. Cytokines, the small protein signaling molecules that constitute the thyroid tumor microenvironment, play significant roles in the facilitation of intercellular communication and the control of tumorigenesis. Also, more attention should be paid to the molecular events within the innate and adaptive immune systems that occur after the organism being exposed to ionizing radiation. Therefore, we implemented a study of 260 patients with DTC in thyroid hormone withdrawal status who were treated with total thyroidectomy to explore the relationship between cytokines and recurrence/active disease status. Besides, we made a cross-sectional study to analyze pre- and post-ablation serum concentration of cytokines of 86 patients with DTC. There was a relationship between clinicohistopathological characteristics of patients with DTC and the presence of cytokines. It is noteworthy that patients with recurrence/active disease were at a higher serum interleukin-2 receptor (IL-2R) level than the disease-free patients (213.59 ± 75.43 pg/ml vs. 186.80 ± 77.40 pg/ml, P = 0.005). Positive correlation was observed between serum IL-2R and thyroglobulin (Tg) (P = 0.003). We also found significant changes in the cytokine profile after radioiodine ablation, including the decrease of tumor necrosis factor-α and IL-8 (P < 0.001, P < 0.001, respectively), and increase of IL-2R (P < 0.001). Thus, we suggest that serum IL-2R may assist in evaluating the disease status during the post-thyroidectomy follow-up and radioiodine therapy has an immunoregulatory effect on serum cytokines.
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Affiliation(s)
- Mengdie Yang
- Department of Nuclear Medicine, Tongji University Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yuzhen Yin
- Shanghai Clinical College, Anhui Medical University, Shanghai, China
| | - Jiajia Zhang
- Department of Nuclear Medicine, Tongji University Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wanwan Yi
- Department of Nuclear Medicine, Tongji University Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jin Liu
- Department of Nuclear Medicine, Tongji University Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Duo Chen
- Department of Nuclear Medicine, Tongji University Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Han Zhang
- Department of Nuclear Medicine, Tongji University Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xin Fan
- Department of Nuclear Medicine, Tongji University Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yu Zhang
- Department of Nuclear Medicine, Tongji University Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Mengqin Zhu
- Department of Nuclear Medicine, Tongji University Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.,Shanghai Clinical College, Anhui Medical University, Shanghai, China
| | - Shanshan Qin
- Department of Nuclear Medicine, Tongji University Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zhongwei Lv
- Department of Nuclear Medicine, Tongji University Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Fei Yu
- Shanghai Clinical College, Anhui Medical University, Shanghai, China.,Institute of Molecular Imaging and Nuclide Therapy, Tongji University School of Medicine, Shanghai, China
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State M, Negreanu L, Voiosu T, Voiosu A, Balanescu P, Mateescu RB. Surrogate markers of mucosal healing in inflammatory bowel disease: A systematic review. World J Gastroenterol 2021; 27:1828-1840. [PMID: 33967560 PMCID: PMC8072191 DOI: 10.3748/wjg.v27.i16.1828] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/02/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mucosal healing (MH) has emerged as a key therapeutic target in inflammatory bowel disease (IBD), and achievement of this goal is documented by endoscopy with biopsy. However, colonoscopy is burdensome and invasive, and substitution with an accurate noninvasive biomarker is desirable. AIM To summarize published data regarding the performance of noninvasive biomarkers in assessing MH in IBD patients. METHODS We conducted a systematic review of studies that reported the performance of biomarkers in diagnosing MH in patients with IBD. The main outcome measure was to review the diagnostic accuracy of serum and fecal markers that showed promising utility in assessing MH. RESULTS We screened 1301 articles, retrieved 46 manuscripts and included 23 articles for full-text analysis. The majority of the included manuscripts referred to fecal markers (12/23), followed by circulatory markers (8/23); only 3/23 of the included manuscripts investigated combined markers (serum and/or fecal markers). Fecal calprotectin (FC) was the most investigated fecal marker for assessing MH. In ulcerative colitis, for cutoff levels ranging between 58 mcg/g and 490 mcg/g, the sensitivity was 89.7%-100% and the specificity was 62%-93.3%. For Crohn's disease, the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g (sensitivity 50%-95.9% and specificity 52.3%-100%). The best performance for a serum marker was observed for the endoscopic healing index, which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein. CONCLUSION Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization.
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Affiliation(s)
- Monica State
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest 020125, Romania
| | - Lucian Negreanu
- Department of Gastroenterology, Emergency University Hospital, Bucharest 050098, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
| | - Theodor Voiosu
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest 020125, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
| | - Andrei Voiosu
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest 020125, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
| | - Paul Balanescu
- Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
- Department of Internal Medicine and Research Methodology, Colentina Clinical Hospital, Bucharest 020125, Romania
| | - Radu Bogdan Mateescu
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest 020125, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania
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Clinical value of assessing serum levels of inflammatory cytokines in the early diagnosis of patients with primary liver carcinoma: a retrospective observational study. JOURNAL OF BIO-X RESEARCH 2021. [DOI: 10.1097/jbr.0000000000000084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Słowińska-Solnica K, Pawlica-Gosiewska D, Gawlik K, Owczarek D, Cibor D, Pocztar H, Mach T, Solnica B. Serum inflammatory markers in the diagnosis and assessment of Crohn's disease activity. Arch Med Sci 2021; 17:252-257. [PMID: 33488879 PMCID: PMC7811324 DOI: 10.5114/aoms/130842] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 11/24/2020] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION The aim of our study was to evaluate the diagnostic characteristics of selected inflammatory markers and the results of multiplication of their concentrations in the diagnosis and assessment of Crohn's disease (CD) activity. METHODS We studied 49 patients with CD and 31 healthy controls. The CD patients were assigned to subgroups with active and inactive disease based on the Crohn's Disease Activity Index score. Serum interleukins and C-reactive protein (CRP) were measured using immunoassays. RESULTS Serum CRP and interleukins: IL-6, IL-17A, IL-23 were significantly higher in the CD group than in controls, with the best diagnostic performance for IL-23. Only serum IL-6 and CRP were significantly higher in active than in inactive disease, with the better performance of CRP. Multiplication results did not perform better than individual multipliers. CONCLUSIONS Serum CRP may be useful in the assessment of CD activity and there is a need for introduction of IL-23 for the CD diagnosis.
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Affiliation(s)
| | | | - Katarzyna Gawlik
- Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland
| | - Danuta Owczarek
- Department of Gastroenterology and Hepatology, Jagiellonian University Medical College, Krakow, Poland
- Department of Gastroenterology and Hepatology, University Hospital, Krakow, Poland
| | - Dorota Cibor
- Department of Gastroenterology and Hepatology, Jagiellonian University Medical College, Krakow, Poland
- Department of Gastroenterology and Hepatology, University Hospital, Krakow, Poland
| | - Halina Pocztar
- Department of Gastroenterology and Hepatology, Jagiellonian University Medical College, Krakow, Poland
- Department of Gastroenterology and Hepatology, University Hospital, Krakow, Poland
| | - Tomasz Mach
- Department of Gastroenterology and Hepatology, Jagiellonian University Medical College, Krakow, Poland
- Department of Gastroenterology and Hepatology, University Hospital, Krakow, Poland
| | - Bogdan Solnica
- Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland
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