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1
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Morandi SC, Herzog EL, Munk M, Kreuzer M, Largiadèr CR, Wolf S, Zinkernagel M, Zysset-Burri DC. The gut microbiome and HLA-B27-associated anterior uveitis: a case-control study. J Neuroinflammation 2024; 21:120. [PMID: 38715051 PMCID: PMC11077820 DOI: 10.1186/s12974-024-03109-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 04/22/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion, disrupts immune equilibrium, and potentially triggers diseases including various human leucocyte antigen (HLA)-B27-associated autoinflammatory and autoimmune diseases such as inflammatory bowel disease (IBD) and spondyloarthropathy (SpA). This study assesses compositional and functional alterations of the GM in patients with HLA-B27-associated non-infectious anterior uveitis (AU) compared to healthy controls. METHODS The gut metagenomes of 20 patients with HLA-B27-associated non-infectious AU, 21 age- and sex-matched HLA-B27-negative controls, and 6 HLA-B27-positive healthy controls without a history of AU were sequenced using the Illumina NovaSeq 6000 platform for whole metagenome shotgun sequencing. To identify taxonomic and functional features with significantly different relative abundances between groups and to identify associations with clinical metadata, the multivariate association by linear models (MaAsLin) R package was applied. RESULTS Significantly higher levels of the Eubacterium ramulus species were found in HLA-B27-negative controls (p = 0.0085, Mann-Whitney U-test). No significant differences in microbial composition were observed at all other taxonomic levels. Functionally, the lipid IVA biosynthesis pathway was upregulated in patients (p < 0.0001, Mann-Whitney U-test). A subgroup analysis comparing patients with an active non-infectious AU to their age- and sex-matched HLA-B27-negative controls, showed an increase of the species Phocaeicola vulgatus in active AU (p = 0.0530, Mann-Whitney U-test). An additional analysis comparing AU patients to age- and sex-matched HLA-B27-positive controls, showed an increase of the species Bacteroides caccae in controls (p = 0.0022, Mann-Whitney U-test). CONCLUSION In our cohort, non-infectious AU development is associated with compositional and functional alterations of the GM. Further research is needed to assess the causality of these associations, offering potentially novel therapeutic strategies.
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Affiliation(s)
- Sophia C Morandi
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
- Department for BioMedical Research, University of Bern, Bern, Switzerland.
| | - Elio L Herzog
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
| | - Marion Munk
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Marco Kreuzer
- Department for BioMedical Research, University of Bern, Bern, Switzerland
- Interfaculty Bioinformatics Unit, University of Bern, Bern, Switzerland
| | - Carlo R Largiadèr
- Department of Clinical Chemistry, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland
| | - Sebastian Wolf
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for BioMedical Research, University of Bern, Bern, Switzerland
| | - Martin Zinkernagel
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for BioMedical Research, University of Bern, Bern, Switzerland
| | - Denise C Zysset-Burri
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for BioMedical Research, University of Bern, Bern, Switzerland
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Estruch JJ, Barken D, Bennett N, Krawiec DK, Ogilvie GK, Powers BE, Polansky BJ, Sueda MT. Evaluation of novel serological markers and autoantibodies in dogs with inflammatory bowel disease. J Vet Intern Med 2020; 34:1177-1186. [PMID: 32282988 PMCID: PMC7255684 DOI: 10.1111/jvim.15761] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 03/13/2020] [Indexed: 12/13/2022] Open
Abstract
Background The use of serological markers to diagnose inflammatory bowel disease (IBD) in humans is well‐established. Because of the frequency of IBD in dogs and resources required for its diagnosis with current methods, new approaches are desired. Objective The goal is to evaluate novel serologic markers to differentiate clinical cohorts in dogs with gastrointestinal (GI) disease and assess their potential to develop a serum‐based IBD diagnostic test. Animals Seventy dogs diagnosed with biopsy‐confirmed IBD, 23 dogs with non‐IBD predominantly acute GI diseases, and 58 normal dogs. Methods Prospective control study. ELISA methods were developed to detect autoantibodies to polymorphonuclear leukocytes (APMNA) and calprotectin (ACNA), antibodies against gliadins (AGA), microbial outer membrane porin C (ACA), and flagellins (AFA) isolated from diseased dogs based on clinical and histopathological scoring. Results IBD dogs displayed a 39%‐76% prevalence of seropositivity against selected serologic markers that markedly decreased to 0%‐13% in non‐IBD and normal dogs. ROC analysis showed statistical significance in differentiating the cohorts, with seropositivity against OmpC being the highest single performance marker. The combination of markers such as OmpC and APMNA reached specificities of 93%‐99% and 79%‐98% and sensitivities of 76%‐97% and 66%‐86% when comparing IBD versus normal cohorts and non‐IBD cohorts, respectively. Conclusion and Clinical Importance Seropositivity of canine immunoglobulins A against selected serologic markers in dogs appears promising in the detection and differentiation of IBD versus other acute GI conditions. Among them, antibody reactivity to Escherichia coli OmpC and canine autoantibodies against polymorphonuclear leukocytes displayed the highest single marker discriminating performance.
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Affiliation(s)
- Juan J Estruch
- Vetica Labs, Inc., 3525 Del Mar Heights Rd. Suite 106, San Diego, California, United States
| | - Derren Barken
- BaseChange Bioinformatics, 7465 Mission Gorge Road Suite #120, San Diego, California, United States
| | - Nicole Bennett
- California Veterinary Specialists Hospital, 2310 Faraday Ave, Carlsbad, California, United States.,California Veterinary Specialists Hospital, 2409 S. Vineyard Ave Suite O, Ontario, California, United States.,California Veterinary Specialists Hospital, 39809 Avenida Acacias, Suite E, Murrieta, California, United States
| | - Donald K Krawiec
- California Veterinary Specialists Hospital, 2310 Faraday Ave, Carlsbad, California, United States.,California Veterinary Specialists Hospital, 2409 S. Vineyard Ave Suite O, Ontario, California, United States.,California Veterinary Specialists Hospital, 39809 Avenida Acacias, Suite E, Murrieta, California, United States
| | - Gregory K Ogilvie
- California Veterinary Specialists Hospital, 2310 Faraday Ave, Carlsbad, California, United States.,California Veterinary Specialists Hospital, 2409 S. Vineyard Ave Suite O, Ontario, California, United States.,California Veterinary Specialists Hospital, 39809 Avenida Acacias, Suite E, Murrieta, California, United States
| | - Barbara E Powers
- CSU, Diagnostic Laboratories, 300 West Drake, Fort Collins, Colorado, United States
| | - Benjamin J Polansky
- California Veterinary Specialists Hospital, 2310 Faraday Ave, Carlsbad, California, United States.,California Veterinary Specialists Hospital, 2409 S. Vineyard Ave Suite O, Ontario, California, United States.,California Veterinary Specialists Hospital, 39809 Avenida Acacias, Suite E, Murrieta, California, United States
| | - Michael T Sueda
- California Veterinary Specialists Hospital, 2310 Faraday Ave, Carlsbad, California, United States.,California Veterinary Specialists Hospital, 2409 S. Vineyard Ave Suite O, Ontario, California, United States.,California Veterinary Specialists Hospital, 39809 Avenida Acacias, Suite E, Murrieta, California, United States
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Kao LT, Lin HC, Lee HC. Inflammatory bowel disease and bipolar disorder: A population-based cross-sectional study. J Affect Disord 2019; 247:120-124. [PMID: 30660021 DOI: 10.1016/j.jad.2019.01.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 12/28/2018] [Accepted: 01/13/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND To date, some experimental studies showed that inflammatory bowel disease (IBD) and bipolar disorder (BD) may share similar biological pathways. Nevertheless, only a few western studies have attempted to demonstrate the potential association between IBD and BD, and relevant findings are still conflicting. Therefore, this cross-sectional study aimed to evaluate the relationship between IBD and BD using a nationwide database in Taiwan. METHOD This study used data from the National Health Insurance Research Database. In total, 3590 patients with IBD and 14,360 propensity score-matched comparison patients without IBD were included in this study. Conditional logistic regressions were performed to evaluate the association between BD and IBD. RESULTS Results showed that BD was found in 26 (0.72%) patients with IBD and in 49 (0.34%) matched comparison patients without IBD. After adjustment, the adjusted odds ratio (OR) of BD for IBD patients was 2.10 (95% confidence interval (CI): 1.30∼3.38) compared to the comparison group. Additionally, this study showed that adjusted OR of BD for ulcerative colitis patients were 2.23 (95% CI: 1.31∼3.82) compared to the comparison group. LIMITATIONS we could not precisely determine the causal association between BD and IBD. CONCLUSIONS We concluded that patients with IBD were more likely to have BD than those comparison patients without IBD.
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Affiliation(s)
- Li-Ting Kao
- Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Sleep Research Center, Taipei Medical University Hospital, Taipei, Taiwan
| | - Herng-Ching Lin
- Sleep Research Center, Taipei Medical University Hospital, Taipei, Taiwan; School of Health Care Administration, Taipei Medical University, Taipei, Taiwan
| | - Hsin-Chien Lee
- Department of Psychiatry, Taipei Medical University-Shuang-Ho Hospital, New Taipei City, Taiwan; Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
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Otoni CC, Heilmann RM, García-Sancho M, Sainz A, Ackermann MR, Suchodolski JS, Steiner JM, Jergens AE. Serologic and fecal markers to predict response to induction therapy in dogs with idiopathic inflammatory bowel disease. J Vet Intern Med 2018; 32:999-1008. [PMID: 29624721 PMCID: PMC5980281 DOI: 10.1111/jvim.15123] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Revised: 11/26/2017] [Accepted: 02/24/2018] [Indexed: 12/14/2022] Open
Abstract
Background Little information is available of markers that assess the disease course in dogs with idiopathic inflammatory bowel disease (IBD). Objectives Evaluate relationship between disease severity and serum and fecal biomarkers in dogs with idiopathic IBD before and after treatment. Animals Sixteen dogs with idioptahic IBD and 13 healthy dogs. Methods Prospective case control study. Canine IBD activity index (CIBDAI) clinical score, serum concentrations of C‐reactive protein (CRP), perinuclear antineutrophil cytoplasmic antibodies (pANCA), and serum and fecal canine calprotectin (cCP) were measured before and after 21 days of treatment. Results Serum CRP (median 3.5 mg/L; range: 0.1‐52.4 mg/L), fecal cCP (median 92.3 μg/g; range: 0.03‐637.5 μg/g), and CIBDAI scores significantly increased in dogs with IBD before treatment compared with serum CRP (median 0.2 mg/L; range: 0.1‐11.8 mg/L; P < .001), fecal cCP (median 0.67 μg/g; range: 0.03‐27.9 μg/g; P < .001) and CIBDAI (P < .001) after treatment. No significant associations between CIBDAI scores and before or after treatment serum biomarkers. There was a significant association between fecal cCP and CIBDAI scores before treatment (rho = 0.60, P = .01). CRP and fecal cCP significantly decreased after treatment (median 3.5 mg/L v. 0.2 mg/L; P < .001 and 92.3 μg/g v. 0.67 μg/g; P = .001, respectively). Conclusions and Clinical Importance Our data indicate that measurement of fecal cCP concentration is a useful biomarker for noninvasive evaluation of intestinal inflammation. Dogs with severe signs of GI disease more often have abnormal markers than dogs having less severe disease.
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Affiliation(s)
- Cristiane C Otoni
- Internal Medicine Department, VCA Arboretum View Animal Hospital, 2551 Warrenville Road, Downers Grove, Illinois
| | - Romy M Heilmann
- Department of Small Animal Clinical Sciences, Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, Texas.,Department of Small Animal Medicine, Small Animal Clinic, College of Veterinary Medicine, University of Leipzig, Leipzig, Saxony, Germany
| | - Mercedes García-Sancho
- Department of Animal Medicine and Surgery, College of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain
| | - Angel Sainz
- Department of Animal Medicine and Surgery, College of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain
| | - Mark R Ackermann
- Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa
| | - Jan S Suchodolski
- Department of Small Animal Clinical Sciences, Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, Texas
| | - Jörg M Steiner
- Department of Small Animal Clinical Sciences, Gastrointestinal Laboratory, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, Texas
| | - Albert E Jergens
- Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, Iowa
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Olbjørn C, Cvancarova Småstuen M, Thiis-Evensen E, Nakstad B, Vatn MH, Perminow G. Serological markers in diagnosis of pediatric inflammatory bowel disease and as predictors for early tumor necrosis factor blocker therapy. Scand J Gastroenterol 2017; 52:414-419. [PMID: 27887202 DOI: 10.1080/00365521.2016.1259653] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To describe the prevalence of serological markers in newly diagnosed treatment-naïve pediatric inflammatory bowel disease (IBD), their utility in differentiating Crohn's disease (CD), ulcerative colitis (UC) and symptomatic non-IBD patients and whether serological markers are associated with early TNF blocker treatment. MATERIAL AND METHODS Ninety-six children and adolescents <18 years, 58 with IBD and 38 symptomatic non-IBD controls were included. At diagnosis and after 1-2 years, serological antibodies (anti-Saccharomyces cerevisiae antibodies (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), flagellin expressed by Clostridial phylum (anti-CBir1), outer membrane porin of Escherichia coli (anti-OmpC), Pseudomonas fluorescens-associated sequence (anti-I2), CRP, ESR and fecal calprotectin were analyzed. The choice of treatment was made at the discretion of the treating pediatrician. RESULTS Of the IBD patients, 20 (36%) and 26 (47%) were positive for ASCA and pANCA compared to 3(8%), p < .01 and 10 (27%), p = .04 of the controls. Thirteen (72%) of UC patients were pANCA positive, versus 13 (35%) of CD patients (p < .01). None of the UC patients was ASCA positive versus 20 (54%) of CD patients (p < .0001). Compared to conventionally treated patients, the 18 (49%) TNF blocker treated CD patients had higher presence of ASCA (p < .01), lower presence of pANCA (p = .02) and higher levels of fecal calprotectin, CRP and ESR at diagnosis. In multivariate analyses ASCA and pANCA status, but not CRP, ESR or calprotectin, were independently associated with early TNF blocker treatment. CONCLUSIONS ASCA and pANCA status were associated with having IBD and with early TNF blocker treatment in CD.
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Affiliation(s)
- Christine Olbjørn
- a Department of Pediatric and Adolescent Medicine , Akershus University Hospital , Lørenskog, Norway.,b Institute for Clinical Medicine, Campus Ahus , University of Oslo , Oslo, Norway
| | | | - Espen Thiis-Evensen
- d Department of Gastroenterology, Rikshospitalet , Oslo University Hospital , Oslo , Norway
| | - Britt Nakstad
- a Department of Pediatric and Adolescent Medicine , Akershus University Hospital , Lørenskog, Norway.,b Institute for Clinical Medicine, Campus Ahus , University of Oslo , Oslo, Norway
| | - Morten Harald Vatn
- e Epigen , Institute for Clinical Medicine, Campus Ahus, University of Oslo , Oslo , Norway
| | - Gøri Perminow
- f Department of Pediatrics, Ullevål , Oslo University Hospital , Oslo , Norway
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Kohashi M, Nishiumi S, Ooi M, Yoshie T, Matsubara A, Suzuki M, Hoshi N, Kamikozuru K, Yokoyama Y, Fukunaga K, Nakamura S, Azuma T, Yoshida M. A novel gas chromatography mass spectrometry-based serum diagnostic and assessment approach to ulcerative colitis. J Crohns Colitis 2014; 8:1010-21. [PMID: 24582087 DOI: 10.1016/j.crohns.2014.01.024] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2013] [Revised: 01/29/2014] [Accepted: 01/29/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS To improve the clinical course of ulcerative colitis (UC), more accurate serum diagnostic and assessment methods are required. We used serum metabolomics to develop diagnostic and assessment methods for UC. METHODS Sera from UC patients, Crohn's disease (CD) patients, and healthy volunteers (HV) were collected at multiple institutions. The UC and HV were randomly allocated to the training or validation set, and their serum metabolites were analyzed by gas chromatography mass spectrometry (GC/MS). Using the training set, diagnostic and assessment models for UC were established by multiple logistic regression analysis. Then, the models were assessed using the validation set. Additionally, to establish a diagnostic model for discriminating UC from CD, the CD patients' data were used. RESULTS The diagnostic model for discriminating UC from HV demonstrated an AUC of 0.988, 93.33% sensitivity, and 95.00% specificity in the training set and 95.00% sensitivity and 98.33% specificity in the validation set. Another model for discriminating UC from CD exhibited an AUC of 0.965, 85.00% sensitivity, and 97.44% specificity in the training set and 83.33% sensitivity in the validation set. The model for assessing UC showed an AUC of 0.967, 84.62% sensitivity, and 88.23% specificity in the training set and 84.62% sensitivity, 91.18% specificity, and a significant correlation with the clinical activity index (rs=0.7371, P<0.0001) in the validation set. CONCLUSIONS Our models demonstrated high performance and might lead to the development of a novel treatment selection method based on UC condition.
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Affiliation(s)
- Michitaka Kohashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
| | - Shin Nishiumi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
| | - Makoto Ooi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
| | - Tomoo Yoshie
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
| | - Atsuki Matsubara
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
| | - Makoto Suzuki
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
| | - Namiko Hoshi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
| | - Koji Kamikozuru
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
| | - Yoko Yokoyama
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
| | - Ken Fukunaga
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
| | - Shiro Nakamura
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
| | - Takeshi Azuma
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan
| | - Masaru Yoshida
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan; The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan; Division of Metabolomics Research, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
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Esmaily H, Sanei Y, Abdollahi M. Autoantibodies and an immune-based rat model of inflammatory bowel disease. World J Gastroenterol 2013; 19:7569-7576. [PMID: 24282347 PMCID: PMC3837255 DOI: 10.3748/wjg.v19.i43.7569] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2013] [Revised: 09/28/2013] [Accepted: 10/13/2013] [Indexed: 02/06/2023] Open
Abstract
The exact causes of inflammatory bowel disease (IBD) are not yet fully defined. From a vast body of literature, we know that the immune response has long been involved in the pathogenesis of IBD, including both ulcerative colitis and Crohn's disease. A variety of specific alterations can lead to immune activation and inflammation directed to the colon, as revealed by some animal models. Current research has focused on the role of antibodies in downstream events and mechanisms of autoimmunity and inflammation. It is not well known whether the production of antibodies is a serologic consequence of IBD, or if it is a result of barrier dysfunction induced by inflammation. Here, we present a new hypothesis to distinguish the complex links between genetic susceptibility, barrier dysfunction, commensal and pathologic microbial factors and inflammatory response (especially autoantibodies) in the pathogenesis of IBD. To ascertain the hypothesis, we developed a pilot model with the concept of the presence of antibodies against enteric bacterial antigens in IBD. Results confirmed our hypothesis. Our hypothesis suggests the possibility of subcutaneous vaccination of animals with administration of all or specific enteric bacterial antigens.
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Saadah OI, Al-Mughales JA. Serological markers of inflammatory bowel disease in children from the Western region of Saudi Arabia. Arab J Gastroenterol 2013; 14:78-82. [PMID: 23820506 DOI: 10.1016/j.ajg.2013.05.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2012] [Revised: 12/28/2012] [Accepted: 05/10/2013] [Indexed: 01/14/2023]
Abstract
BACKGROUND AND STUDY AIMS Serological markers including peri-nuclear anti-neutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) have been reported in relation to inflammatory bowel disease (IBD). The aim of this study was to ascertain the prevalence and diagnostic accuracy of pANCA and ASCA antibodies in Saudi children with IBD. PATIENTS AND METHODS A retrospective case-control study of children with IBD seen at King Abdulaziz University Hospital, Jeddah, between September 2002 and February 2012. RESULTS The study included 131 patients with IBD (86 Crohn's disease (CD) and 45 ulcerative colitis (UC)) and 67 non-IBD control subjects. Females comprised 51% of CD, 60% of UC and 52% of non-IBD controls. The mean age was 10.7±5.2years for CD, 8.9±5years for UC, and 11.2±6.8years for the non-IBD controls. Positive ASCA-IgA and ASCA-IgG were detected in 35.8% and 35% of CD patients and in 5.8% and 3.7% of the non-IBD controls, respectively. The pANCA was detected in 28.9% of UC patients and in none of the non-IBD controls. The pANCA recognised the myeloperoxidase (MPO) antibody in 36.4% of the patients with UC. No significant difference in the frequency of pANCA between extensive disease and disease limited to the rectosigmoid colon (p=0.48), and no significant difference in the ASCAs antibodies in patients with or without involvement of the terminal ileum (p=0.81). CONCLUSION The prevalence of ASCA and pANCA antibodies was low in Saudi children with IBD. Therefore, it may not be useful as a screening tool for IBD but it may be employed to aid the diagnosis in clinically suspected cases.
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Affiliation(s)
- Omar I Saadah
- Department of Paediatrics, Division of Gastroenterology, Faculty of Medicine, King Abdulaziz University Hospital, King Abdulaziz University, Jeddah, Saudi Arabia.
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Abstract
Inflammatory bowel disease (IBD) is a heterogeneous group of chronic inflammatory disorders of the gastrointestinal tract with two main distinguishable entities, Crohn’s disease (CD) and ulcerative colitis (UC). IBD-unclassified (IBD-U) is a diagnosis that covers the “grey” zone of diagnostic uncertainty between UC and CD. Current diagnosis of IBD relies on the clinical, endoscopic, radiological, histological and biochemical features, but this approach has shortcomings especially in cases of overlapping symptoms of CD and UC. The need for a diagnostic tool that would improve the conventional methods in IBD diagnosis directed the search towards potential immunological markers, since an aberrant immune response against microbial or endogenous antigens in a genetically susceptible host seems to be implicated in IBD pathogenesis. The spectrum of antibodies to different microbial antigens and autoantibodies associated with IBD is rapidly expanding. Most of these antibodies are associated with CD like anti-glycan antibodies: anti-Saccharomices cerevisiae (ASCA) and the recently described anti-laminaribioside (ALCA), anti-chitobioside (ACCA), anti-mannobioside (AMCA), anti-laminarin (anti-L) and anti-chitin (anti-C) antibodies; in addition to other antibodies that target microbial antigens: anti-outer membrane porin C (anti-OmpC), anti-Cbir1 flagellin and anti-I2 antibody. Also, autoantibodies targeting the exocrine pancreas (PAB) were shown to be highly specific for CD. In contrast, UC has been associated with anti-neutrophil cytoplasmic autoantibodies (pANCA) and antibodies against goblet cells (GAB). Current evidence suggests that serologic panels of multiple antibodies are useful in differential diagnosis of CD versus UC and can be a valuable aid in stratifying patients according to disease phenotype and risk of complications.
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Affiliation(s)
- Andrea Tesija Kuna
- University Department of Chemistry, Medical School University Hospital Sestre Milosrdnice, Zagreb, Croatia.
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10
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Del Valle-Pinero AY, Van Deventer HE, Fourie NH, Martino AC, Patel NS, Remaley AT, Henderson WA. Gastrointestinal permeability in patients with irritable bowel syndrome assessed using a four probe permeability solution. Clin Chim Acta 2013; 418:97-101. [PMID: 23328210 PMCID: PMC3594104 DOI: 10.1016/j.cca.2012.12.032] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2012] [Revised: 12/31/2012] [Accepted: 12/31/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND Abnormal gastrointestinal permeability has been linked to irritable bowel syndrome (IBS). The lactulose-to-mannitol ratio is traditionally used to assess small intestine permeability while sucralose and sucrose are used to assess colonic and gastric permeability respectively. We used a single 4-probe test solution to assess permeability throughout the gastrointestinal tract in IBS patients and healthy controls by measuring the recovery of the probes in urine after ingestion using a modified liquid chromatography mass spectrometry protocol. METHODS Fasting participants (N=59) drank a permeability test solution (100ml: sucralose, sucrose, mannitol, and lactulose). Urine was collected over a 5-h period and kept frozen until analysis. Urinary sugar concentrations were measured using a liquid chromatography/triple quadruple mass spectrometer. RESULTS Colonic permeability was significantly lower in IBS patients when compared to healthy controls (p=0.011). Gastric and small intestinal permeability did not significantly differ between the groups. CONCLUSIONS The study demonstrates the clinical potential of this non-invasive method for assessing alterations in gastrointestinal permeability in patients with IBS.
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Affiliation(s)
| | - Hendrick E. Van Deventer
- Department of Laboratory Medicine, NIH, DHHS, Bethesda, MD
- Warren Grant Magnuson Clinical Center, NIH, DHHS, Bethesda, MD
| | - Nicolaas H. Fourie
- Biobehavioral Branch, Intramural Research Program, NINR, NIH, DHHS, Bethesda, MD
| | - Angela C. Martino
- Biobehavioral Branch, Intramural Research Program, NINR, NIH, DHHS, Bethesda, MD
| | - Nayan S. Patel
- Biobehavioral Branch, Intramural Research Program, NINR, NIH, DHHS, Bethesda, MD
| | - Alan T. Remaley
- Department of Laboratory Medicine, NIH, DHHS, Bethesda, MD
- Warren Grant Magnuson Clinical Center, NIH, DHHS, Bethesda, MD
| | - Wendy A. Henderson
- Biobehavioral Branch, Intramural Research Program, NINR, NIH, DHHS, Bethesda, MD
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11
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Roggenbuck D, Reinhold D, Wex T, Goihl A, von Arnim U, Malfertheiner P, Büttner T, Porstmann T, Porstmann S, Liedvogel B, Bogdanos DP, Laass MW, Conrad K. Autoantibodies to GP2, the major zymogen granule membrane glycoprotein, are new markers in Crohn's disease. Clin Chim Acta 2010; 412:718-24. [PMID: 21195704 DOI: 10.1016/j.cca.2010.12.029] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2010] [Revised: 12/21/2010] [Accepted: 12/21/2010] [Indexed: 12/28/2022]
Abstract
BACKGROUND Crohn's disease (CD) is an inflammatory bowel disease (IBD) characterized by reactivity against microbial and self antigens. Zymogen granule glycoprotein 2 (GP2) was identified as the major autoantigen of CD-specific pancreatic autoantibodies (PAB). METHODS Human GP2 was expressed in the Spodoptera frugiperda 9 (Sf9) cell line using the baculovirus system, purified by Ni-chelate chromatography, and used as antigen for anti-GP2 IgA and IgG assessment by enzyme-linked immunosorbent assays (ELISA). Antibodies to mannan of Saccharomyces cerevisiae (ASCA), PAB, and anti-GP2 were investigated in sera of 178 CD patients, 100 ulcerative colitis (UC) patients, and 162 blood donors (BD). RESULTS Anti-GP2 IgG and IgA were found in 48/72 (66.7%) and 23/72 (31.9%) PAB positive and 5/106 (4.7%) and 1/106 (0.9%) PAB negative CD patients (p<0.0001), respectively. CD patients displayed significantly higher reactivity to GP2 than UC patients and BD (p<0.0001), respectively. Occurrence of anti-GP2 antibodies correlated with PAB reactivity (Spearmen's rho=0.493, p<0.00001). There was a significant relationship between the occurrence of ASCA IgG and anti-GP2 IgG (p=0.0307). CONCLUSIONS Anti-GP2 IgG and IgA constitute novel CD specific autoantibodies, the quantification of which could improve the serological diagnosis of IBD.
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Affiliation(s)
- Dirk Roggenbuck
- GA Generic Assays GmbH, 15827 Dahlewitz, Ludwig-Erhard Ring 3, Germany.
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12
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Benor S, Russell GH, Silver M, Israel EJ, Yuan Q, Winter HS. Shortcomings of the inflammatory bowel disease Serology 7 panel. Pediatrics 2010; 125:1230-6. [PMID: 20439597 DOI: 10.1542/peds.2009-1936] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE The goal was to compare the predictive values of the Prometheus Inflammatory Bowel Disease (IBD) Serology 7 (IBD7) panel (Prometheus Laboratories, San Diego, CA) with the predictive values of routine blood tests in a population of children referred for initial evaluation of suspected IBD. METHODS Medical records of pediatric patients referred for evaluation of IBD for whom IBD7 testing was performed at Prometheus Laboratories between January 2006 and November 2008 were reviewed. Patients underwent diagnosis by pediatric gastroenterologists on the basis of clinical, radiologic, endoscopic, and pathologic evaluations. RESULTS A total of 394 records were identified. We excluded 90 records on the basis of age of >21 years, previous diagnosis of IBD, or unclear diagnosis. The prevalence of IBD in this cohort was 38%. The sensitivity, specificity, positive predictive value, negative predictive value, and kappa value for the serological panel were 67%, 76%, 63%, 79%, and 42%, respectively, compared with values for a combination of 3 abnormal routine laboratory test results of 72%, 94%, 85%, 79%, and 47%. The antiflagellin antibody assay, the newest assay added to the panel, had sensitivity of 50% and specificity of 53%. Repeat serological testing failed to produce consistent results for 4 of 10 patients. CONCLUSION Despite its recent inclusion of the antiflagellin assay, the IBD7 panel has lower predictive values than routine laboratory tests in pediatric screening for IBD.
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Affiliation(s)
- Shira Benor
- Department of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Hardvard University, Boston, MA, USA.
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13
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Biological markers in inflammatory bowel disease: Practical consideration for clinicians. ACTA ACUST UNITED AC 2009; 33 Suppl 3:S158-73. [DOI: 10.1016/s0399-8320(09)73151-3] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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14
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Serological markers are associated with disease course in ulcerative colitis. A study in an unselected population-based cohort followed for 10 years. J Crohns Colitis 2008; 2:114-22. [PMID: 21172201 DOI: 10.1016/j.crohns.2007.10.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2007] [Accepted: 10/17/2007] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) have been proposed as markers for diagnosis and for subtyping of inflammatory bowel disease (IBD). The aim of this study was to investigate the association of p-ANCA and ASCA with a 10-year disease outcome in terms of cumulative rate of colectomy and relapse in a population-based European inception cohort of ulcerative colitis (UC) patients. METHODS Serum samples from 432 consenting patients were analysed for p-ANCA and ASCA. The results were compared with the cumulative colectomy rate, relapsing disease and total number of relapses. We used multiple regression analyses adjusted for age, sex, residence, disease extent at diagnosis, smoking, familial IBD and drug treatment to study the relationship between serological values and disease course. RESULTS The relapse rate was higher in the p-ANCA-positive patients: 82% (95% confidence interval [CI] 75-89%) compared with 67% (CI 62-72%, p=0.011) in the p-ANCA-negative patients. The risk of relapsing disease course was higher by a factor of 1.4 (CI 1.1-1.8, p=0.009) for p-ANCA-positive patients than for p-ANCA-negative patients, and the corresponding relative risk (RR) for the total number of relapses was 1.9 (CI 1.7-2.1, p<0.001). In ASCA-positive patients RR for the total number of relapses was 1.8 (CI 1.5-2.1, p<0.001). No significant association with colectomy rate was found for the presence of either p-ANCA or ASCA. CONCLUSION UC patients positive for p-ANCA and possibly for ASCA may have a more unfavourable long-term disease outcome in terms of relapse than UC patients without these markers.
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15
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Perinuclear antineutrophil cytoplasmic autoantibodies and anti-Saccharomyces cerevisiae antibodies as serological markers are not specific in the identification of Crohn's disease and ulcerative colitis. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2008; 22:33-6. [PMID: 18209778 DOI: 10.1155/2008/974540] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
OBJECTIVE To evaluate the diagnostic accuracy of perinuclear antineutrophil cytoplasmic autoantibodies (pANCAs) and anti-Saccharomyces cerevisiae antibodies (ASCAs), as single agents and in combination, for the diagnosis of Crohn's disease (CD) and ulcerative colitis (UC), including in cases of indeterminate colitis (IC). METHODS The sera from a total of 98 patients were studied: 77 with CD, 16 with UC and five with IC. The medical records of these patients were reviewed for disease diagnosis, demographic data, and patient symptoms and medications. ELISAs were utilized to detect the presence of ASCAs and deoxyribonuclease-sensitive pANCAs, and these results were then compared with the patients' clinical data. RESULTS For UC, a positive pANCA test alone provided a sensitivity of 50% and a specificity of 82%. For CD, a positive ASCA test alone provided a sensitivity of 40% and a specificity of 100%. A combination of pANCA-positive and ASCA-negative results showed a sensitivity of 50% and specificity of 90% for the diagnosis of UC. Similarly, the combination of ASCA-positive and pANCA-negative results provided a sensitivity and specificity of 32% and 100% for the diagnosis of CD, respectively. Interestingly, 80% of IC patients showed serology results consistent with UC. CONCLUSIONS Although this combination of serological markers provides a diagnostic tool with generally high specificities, the low sensitivities of these serological markers, most notably in terms of CD, preclude the possibility that they can replace the tools currently used for inflammatory bowel disease diagnosis and management. It is possible, however, that these serological markers may prove beneficial in the management of IC.
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16
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Papp M, Altorjay I, Lakatos PL. [Relevance of serologic studies in inflammatory bowel diseases]. Orv Hetil 2007; 148:887-896. [PMID: 17478404 DOI: 10.1556/oh.2007.28064] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The panel of serologic markers for inflammatory bowel diseases (IBDs) is rapidly expanding. Although anti- Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmic antibodies (atypical P-ANCA) remain the most widely investigated, an increasing amount of experimental data is available on newly discovered antibodies directed against various microbial antigens. Such antibodies include anti-OmpC (outer membrane porin C), anti- Pseudomonas fluorescens (anti-I2) and antiglycan antibodies (anti-laminaribioside carbohydrate antibody [ALCA]), anti-chitobioside carbohydrate antibody [ACCA]), anti-mannobioside carbohydrate antibody [AMCA]) and anti-CBir1; this latter is the first bacterial antigen to induce colitis in animal models of IBD and also leads to a pathological immune response in IBD patients (anti-flagellin antibody). The role of assessment of various antibodies in the current diagnostic algorithm of IBD is rather questionable due to their limited sensitivity. In contrast, the association of serologic markers with disease behavior and phenotype is getting more into the focus of interest. An increasing number of observations confirm that patients with Crohn's disease expressing multiple serologic markers at high titers are more likely to have complicated small bowel disease (e.g. stricture and/or perforation) and are at higher risk for surgery than those without, or with low titer of antibodies. Creating homogenous disease sub-groups based on serologic response may help develop more standardized therapeutic approaches and may help in a better understanding of the pathomechanism of IBD. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD.
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Affiliation(s)
- Mária Papp
- Debreceni Egyetem, Orvos- és Egészségtudományi Centrum Belgyógyászati Intézet, Gasztroenterológiai Tanszék, Debrecen.
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Papp M, Norman GL, Altorjay I, Lakatos PL. Utility of serological markers in inflammatory bowel diseases: gadget or magic? World J Gastroenterol 2007; 13:2028-2036. [PMID: 17465443 PMCID: PMC4319120 DOI: 10.3748/wjg.v13.i14.2028] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2007] [Revised: 03/02/2007] [Accepted: 03/12/2007] [Indexed: 02/06/2023] Open
Abstract
The panel of serologic markers for inflammatory bowel diseases (IBD) is rapidly expanding. Although anti-Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) remain the most widely investigated, an increasing amount of experimental data is available on newly discovered antibodies directed against various microbial antigens. The role of the assessment of various antibodies in the current IBD diagnostic algorithm is often questionable due to their limited sensitivity. In contrast, the association of serologic markers with disease behavior and phenotype is becoming increasingly well-established. An increasing number of observations confirms that patients with Crohn's disease expressing multiple serologic markers at high titers are more likely to have complicated small bowel disease (e.g. stricture and/or perforation) and are at higher risk for surgery than those without, or with low titers of antibodies. Creating homogenous disease sub-groups based on serologic response may help develop more standardized therapeutic approaches and may help in a better understanding of the pathomechanism of IBD. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD.
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18
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Cousins L, Graham M, Tooze R, Carter C, Miller JR, Powrie FM, Macpherson GG, Butcher GW. Eosinophilic bowel disease controlled by the BB rat-derived lymphopenia/Gimap5 gene. Gastroenterology 2006; 131:1475-85. [PMID: 17064701 DOI: 10.1053/j.gastro.2006.09.023] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2006] [Accepted: 07/21/2006] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS Many models of autoimmunity are associated with lymphopenia. Most involve a T-helper cell (Th)1-type disease, including the diabetic BioBreeding (BB) rat. To investigate the roles of identified susceptibility loci in disease pathogenesis, we bred PVG-RT1(u), lymphopenia (lyp)/lyp rats, congenic for the iddm1 (RT1(u)) and iddm2 (lyp, Gimap5(-/-)) diabetes susceptibility loci on the PVG background. Surprisingly, these rats developed a spontaneous, progressive, inflammatory bowel disease. To understand the disease pathogenesis, we undertook investigations at the genetic, histologic, and cellular levels. METHODS Genetically lymphopenic rats and congenic wild-type partners were compared for gross pathologic, histologic, and immunologic parameters, the latter including cytokines and autoantibodies. RESULTS Genetic analysis demonstrated that homozygosity at the lyp locus was required for disease. All rats developed disease, and the median age at humane killing was approximately 36 weeks. This panintestinal disease showed a conspicuous eosinophilic infiltrate in the submucosa and muscle layers, but the villi were unaffected. Diseased rats showed splenomegaly and massive enlargement of the mesenteric lymph nodes. This pathology resembles human eosinophilic gastroenteritis, and several further features indicate a Th2 basis. The rats developed high serum IgE and made IgG autoantibodies that detected a nonleukocytic cell present in the intestinal wall of all rats (including germ free). CONCLUSIONS The T-lymphopenic state associated with GIMAP5 deficiency renders rats generally susceptible to T-cell-mediated autoimmunity, but the immunoregulatory bias (Th1/Th2) of any disease depends on other genetic (or environmental) factors. In the present model, we suggest that defective peripheral tolerance to an intestine-specific autoantigen leads to uncontrolled inflammation of the intestinal wall.
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Affiliation(s)
- Lesley Cousins
- The Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
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19
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Reese GE, Constantinides VA, Simillis C, Darzi AW, Orchard TR, Fazio VW, Tekkis PP. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Am J Gastroenterol 2006; 101:2410-22. [PMID: 16952282 DOI: 10.1111/j.1572-0241.2006.00840.x] [Citation(s) in RCA: 176] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIMS The aim of this study was to assess the diagnostic precision of antiSaccharomyces cerevisiae (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) in inflammatory bowel disease (IBD) and evaluate their discriminative ability between ulcerative colitis (UC) and Crohn's disease (CD). METHODS Meta-analysis of studies reporting on ASCA and pANCA in IBD was performed. Sensitivity, specificity, and likelihood ratios (LR+, LR-) were calculated for different test combinations for CD, UC, and for IBD compared with controls. Meta-regression was used to analyze the effect of age, DNAse, colonic CD, and assay type. RESULTS Sixty studies comprising 3,841 UC and 4,019 CD patients were included. The ASCA+ with pANCA- test offered the best sensitivity for CD (54.6%) with 92.8% specificity and an area under the ROC (receiver operating characteristic) curve (AUC) of 0.85 (LR+ = 6.5, LR- = 0.5). Sensitivity and specificity of pANCA+ tests for UC were 55.3% and 88.5%, respectively (AUC of 0.82; LR+ = 4.5, LR- = 0.5). Sensitivity and specificity were improved to 70.3% and 93.4% in a pediatric subgroup when combined with an ASCA- test. Meta-regression analysis showed decreased diagnostic precision of ASCA for isolated colonic CD (RDOR = 0.3). CONCLUSIONS ASCA and pANCA testing are specific but not sensitive for CD and UC. It may be particularly useful for differentiating between CD and UC in the pediatric population.
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Affiliation(s)
- George E Reese
- Department of Biosurgery and Surgical Technology, Imperial College London, St Mary's Hospital, London, United Kingdom
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20
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Dendrinos KG, Becker JM, Stucchi AF, Saubermann LJ, LaMorte W, Farraye FA. Anti-Saccharomyces cerevisiae antibodies are associated with the development of postoperative fistulas following ileal pouch-anal anastomosis. J Gastrointest Surg 2006; 10:1060-4. [PMID: 16843878 DOI: 10.1016/j.gassur.2006.02.004] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2005] [Revised: 01/17/2006] [Accepted: 02/22/2006] [Indexed: 01/31/2023]
Abstract
Although serologic testing for perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) is reportedly useful in distinguishing ulcerative colitis (UC) from Crohn's disease (CD), there are few and conflicting reports assessing their utility in predicting postoperative complications after ileal pouch-anal anastomosis (IPAA). We examined the associations between postoperative complications such as pouchitis or fistulas and pANCA and ASCA antibodies in a group of patients who underwent IPAA for UC. We conducted a retrospective chart review of 34 patients initially diagnosed with UC (four of these patients had a diagnosis of indeterminate colitis) who underwent IPAA by a single surgeon, and who had pANCA and ASCA antibody levels measured during their clinical course. Study patients were assigned to four groups based on the pattern of antibody reactivity: pANCA+/ASCA- (16 patients), pANCA-/ASCA+ (nine patients), pANCA+/ASCA+ (five patients), and pANCA-/ASCA- (four patients). The median length of follow-up was 16 months (3-144 months). None of the patients (0 of 16) who were pANCA+/ASCA- had their preoperative diagnosis of UC changed after a median follow-up of 14 months (3-118 months). Of the nine patients with a preoperative diagnosis of UC who were pANCA-/ASCA+, four patients (44%) had their diagnosis changed postoperatively to CD based on clinical findings, with a median follow-up: 15 months (5-98 months). Of 16 patients who underwent IPAA and who were pANCA+/ASCA-, 15 of 16 (93.75%), were free of fistulas postoperatively, with a median follow-up of 14 months (3-118 months). Of nine patients with a preoperative diagnosis of UC who underwent IPAA and who were pANCA-/ASCA+, four of nine (44%; p = 0.04) developed fistulas postoperatively, with a median length of follow-up of 55 months (15-67 months). No relationship between serologic profiles or antibody titer levels and the development of pouchitis was identified. In a cohort of patients undergoing IPAA for UC, serologic profiles may be useful in identifying patients at risk of postoperative fistula formation. Patients who were pANCA-/ASCA+ were at increased risk for the development of fistulas postoperatively compared to patients who were pANCA+/ASCA-, and were also more likely to have their diagnosis changed postoperatively to CD. A larger study is needed to validate these observations.
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Affiliation(s)
- Kleanthis G Dendrinos
- Section of Gastroenterology, Boston Medical Center, Boston, Massachusetts 02118, USA
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21
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Mei L, Targan SR, Landers CJ, Dutridge D, Ippoliti A, Vasiliauskas EA, Papadakis KA, Fleshner PR, Rotter JI, Yang H. Familial expression of anti-Escherichia coli outer membrane porin C in relatives of patients with Crohn's disease. Gastroenterology 2006; 130:1078-85. [PMID: 16618402 DOI: 10.1053/j.gastro.2006.02.013] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2005] [Accepted: 01/04/2006] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Crohn's disease (CD) is a genetically complex disorder with strong familial aggregation. Pathogenesis appears to involve dysregulation of the immune response to endogenous bacteria. Anti-Escherichia coli outer membrane porin C (anti-OmpC) expression reflects an exaggerated response to commensal bacteria and occurs with higher frequency in CD. The aim of this study was to determine whether there is familial aggregation and genetic determination of anti-OmpC expression in CD families. METHODS Study groups consisted of 787 CD patients, 389 ulcerative colitis (UC) patients, 619 unaffected relatives, and 216 healthy controls. Serum anti-OmpC was detected by enzyme-linked immunosorbent assay. RESULTS CD patients had a greater percentage of anti-OmpC than UC patients and healthy controls. Anti-OmpC expression was more frequent in unaffected relatives from CD-only or mixed families, compared with healthy controls (P = .002 and .0001, respectively), and it was more frequent in UC patients from mixed families than those from UC-only families (P = .02). There was a significant familiality in anti-OmpC expression: P = .02 for qualitative concordance and P < .0001 for quantitative intraclass correlation. The heritability estimate for anti-OmpC level was .39 (P < .0001). CONCLUSIONS Anti-OmpC is a heritable immunophenotype. Increased anti-OmpC expression in the unaffected family members of CD patients suggests that anti-OmpC may be an immunologic risk marker for CD. That UC patients in mixed families had a higher response to OmpC than those in UC-only families indicates pathophysiologic heterogeneity within UC.
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Affiliation(s)
- Ling Mei
- Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA
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Luckschander N, Allenspach K, Hall J, Seibold F, Gröne A, Doherr MG, Gaschen F. Perinuclear Antineutrophilic Cytoplasmic Antibody and Response to Treatment in Diarrheic Dogs with Food Responsive Disease or Inflammatory Bowel Disease. J Vet Intern Med 2006. [DOI: 10.1111/j.1939-1676.2006.tb02849.x] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
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Koutroubakis IE, Drygiannakis D, Karmiris K, Drygiannakis I, Makreas S, Kouroumalis EA. Pancreatic autoantibodies in Greek patients with inflammatory bowel disease. Dig Dis Sci 2005; 50:2330-4. [PMID: 16416183 DOI: 10.1007/s10620-005-3056-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2005] [Accepted: 03/15/2005] [Indexed: 12/20/2022]
Abstract
Pancreatic autoantibodies (PAbs) have been suggested as a specific but not sensitive marker for Crohn's disease (CD). The aim of this study was to assess the value of detecting PAbs in Greek patients with ulcerative colitis (UC) and CD. Sera were collected from 150 patients with IBD (73 with UC and 77 with CD), 31 cases with non-IBD intestinal inflammation, 16 cases with other autoimmune diseases, and 104 healthy controls. Determination of PAbs was performed by a standard indirect immunofluorescence technique. PAbs were detected in 18 of 73 (24.7%) samples from UC patients and in 32 of 77 (41.6%) samples from CD patients. The prevalence of positive PAbs was significantly higher in CD than in UC (P = 0.04). None of the 104 samples from healthy controls and the 31 cases with non-IBD intestinal inflammation had detectable PAbs. One patient with Sjogren's syndrome was PAbs positive. No association of PAbs with IBD activity, IBD localization, or medical treatment was found. Patients with stenotic CD had a significantly higher prevalence of PAbs positivity (60%) compared with patients with inflammatory (28.6%) and fistulizing (41.2%) disease (P = 0.02). The prevalence of PAbs in Greek CD patients was found to be similar to that in previous reports. In contrast to these studies we found also increased prevalence of PAbs in UC patients. These findings suggest that PAbs should be considered as a specific marker for IBD rather than for CD.
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Routine testing of folate levels in geriatric assessment for dementia. J Am Geriatr Soc 1988; 497:141-146. [PMID: 3136199 DOI: 10.1016/j.cca.2019.07.033] [Citation(s) in RCA: 30] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 07/26/2019] [Accepted: 07/26/2019] [Indexed: 12/16/2022]
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