|
1
|
Yorulmaz E, Adalı G, Yorulmaz H, Taşan G, Gürses S, Ayaş MR, Tuncer İ. The Correlation between New Serological Markers and Disease Phenotype and Activation in Inflammatory Bowel Disease. Middle East J Dig Dis 2022; 14:294-303. [PMID: 36619271 PMCID: PMC9489435 DOI: 10.34172/mejdd.2022.286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 06/07/2022] [Indexed: 11/06/2022] Open
Abstract
Background: The aim of the study is to assess the correlation between a new antibody panel that is developed against glycans on Crohn's disease (CD) and ulcerative colitis (UC) differentiative diagnosis and disease properties. Methods: In the study, 137 CD and 122 UC patients and 90 controls were included. Anti-saccharomyces cerevisiae IgG (ASCA), anti-laminaribioside IgG (ALCA), anti-chitobioside IgA (ACCA), and anti-mannobioside IgG (AMCA) were tested in serum. Results: While at least 1 of the other 3 serological markers was positive in 89% of ASCA-positive patients, at least 1 of the other 3 serological markers was positive in 77% of ASCA-negative patients. Positivity ratio for a single anticarbohydrate was ALCA 18 (22%), ACCA 5 (12%), and AMCA 16 (23%). A significant correlation was found between ASCA positivity (P<0.001) in operated patients and between ASCA, ALCA, and ACCA positivity (P<0.05) in patients with stricturing and fistulizing CD. According to the ROC analysis, ASCA was found to have the highest area under the curve (0.70-0.82) (correlation coefficient interval 95%). A significant correlation was found between ASCA, ALCA, and ACCA positivity and high serum antibody levels and disease activation (P<0.05). Conclusion: ASCA, ALCA, and ACCA were found to be correlated with the disease complication and activation in CD. ASCA and ALCA were determined as the best markers in the differentiation between CD and UC.
Collapse
Affiliation(s)
- Elif Yorulmaz
- Department of Gastroenterology, University of Health Sciences, Bağcılar Training and Research Hospital, Istanbul, Turkey,Corresponding Author: Elif Yorulmaz, MD Department of Gastroenterology, University of Health Sciences, Bağcılar Training and Research Hospital, İstanbul, Turkey Tel:+90 0212 440 40 00 Fax:+90 0212 440 42 42
| | - Gupse Adalı
- Department of Gastroenterology, University of Health Sciences, Umraniye Training and Research Hospital, Istanbul, Turkey
| | - Hatice Yorulmaz
- Faculty of Health Sciences, Haliç University, Eyüp, İstanbul, Turkey
| | - Güralp Taşan
- Department of Gastroenterology, Istanbul Medeniyet University, School of Medicine, Goztepe, Istanbul, Turkey
| | - Seval Gürses
- Department of Biology, Trakya University, Edirne, Turkey
| | | | - İlyas Tuncer
- Department of Gastroenterology, Istanbul Medeniyet University, School of Medicine, Goztepe, Istanbul, Turkey
| |
Collapse
|
|
2
|
Ranjbar R, Ghasemian M, Maniati M, Hossein Khatami S, Jamali N, Taheri-Anganeh M. Gastrointestinal disorder biomarkers. Clin Chim Acta 2022; 530:13-26. [DOI: 10.1016/j.cca.2022.02.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/11/2022] [Accepted: 02/15/2022] [Indexed: 01/19/2023]
|
|
3
|
Lee SH, Turpin W, Espin-Garcia O, Raygoza Garay JA, Smith MI, Leibovitzh H, Goethel A, Turner D, Mack D, Deslandres C, Cino M, Aumais G, Panaccione R, Jacobson K, Bitton A, Steinhart AH, Huynh HQ, Princen F, Moayyedi P, Griffiths AM, Silverberg MS, Paterson AD, Xu W, Croitoru K. Anti-Microbial Antibody Response is Associated With Future Onset of Crohn's Disease Independent of Biomarkers of Altered Gut Barrier Function, Subclinical Inflammation, and Genetic Risk. Gastroenterology 2021; 161:1540-1551. [PMID: 34293299 DOI: 10.1053/j.gastro.2021.07.009] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 06/28/2021] [Accepted: 07/13/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Altered host immune reactivity to microbial antigens is hypothesized to trigger the onset of Crohn's disease (CD). We aimed to assess whether increased serum anti-microbial antibody response in asymptomatic first-degree relatives (FDRs) of CD patients is an independent risk factor for future CD development. METHODS We measured host serum antibody response to 6 microbial antigens at enrollment (Prometheus enzyme-linked immunosorbent assay test: anti-Saccharomyces cerevisiae antibodies immunoglobulin A/immunoglobulin G, anti-OmpC, anti-A4-Fla2, anti-FlaX, anti-CBir1) and derived the sum of positive antibodies (AS). We used samples at enrollment of prospectively followed healthy FDRs from a nested case-control cohort of the Crohn's and Colitis Canada Genetics Environment Microbial Project. Those who later developed CD (n = 77) were matched 1:4 by age, sex, follow-up duration, and geographic location with control FDRs remaining healthy (n = 307). To address our research aims, we fitted a multivariable conditional logistic regression model and performed causal mediation analysis. RESULTS High baseline AS (≥2) (43% of cases, 11% of controls) was associated with higher risk of developing CD (adjusted odds ratio, 6.5; 95% confidence interval, 3.4-12.7; P < .001). Importantly, this association remained significant when adjusted for markers of gut barrier function, fecal calprotectin, C-reactive protein, and CD-polygenic risk score, and in subjects recruited more than 3 years before diagnosis. Causal mediation analysis showed that the effect of high AS on future CD development is partially mediated (42%) via preclinical gut inflammation. CONCLUSIONS Our results suggest that increased anti-microbial antibody responses are associated with risk of future development of CD, independent of biomarkers of abnormal gut barrier function, subclinical inflammation, and CD-related genetic risks. This suggests that anti-microbial antibody responses are an early predisease event in the development of CD.
Collapse
Affiliation(s)
- Sun-Ho Lee
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Williams Turpin
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Osvaldo Espin-Garcia
- Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto and Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Juan Antonio Raygoza Garay
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Michelle I Smith
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Haim Leibovitzh
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Ashleigh Goethel
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada
| | - Dan Turner
- The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - David Mack
- Division of Gastroenterology, Hepatology & Nutrition, Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada
| | - Colette Deslandres
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, CHU Sainte-Justine, University of Montreal, Quebec, Canada
| | - Maria Cino
- Division of Gastroenterology, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Guy Aumais
- Hôpital Maisonneuve-Rosemont, Department of Medicine, University of Montreal, Montreal, Quebec, Canada
| | - Remo Panaccione
- Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
| | - Kevan Jacobson
- Canadian Gastro-Intestinal Epidemiology Consortium, Canada, British Columbia Children's Hospital, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada
| | - Alain Bitton
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - A Hillary Steinhart
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Hien Q Huynh
- Division of Gastroenterology and Nutrition, Stollery Children's Hospital, University of Alberta, Edmonton, Alberta, Canada
| | | | - Paul Moayyedi
- Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Anne M Griffiths
- Division of Gastroenterology, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Mark S Silverberg
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Andrew D Paterson
- Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto and Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; Genetics and Genome Biology, The Hospital for Sick Children Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Wei Xu
- Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto and Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
| | - Kenneth Croitoru
- Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Gastroenterology & Hepatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
| | | |
Collapse
|
|
4
|
Kim MJ, Kim E, Kang B, Lee Y, Kang ES, Choe YH. Anti- Saccharomyces cerevisiae Antibody in Pediatric Crohn's Disease Patients without Mucosal Healing Is a Useful Marker of Mucosal Damage. Gut Liver 2021; 15:763-770. [PMID: 33376230 PMCID: PMC8444098 DOI: 10.5009/gnl20212] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 09/24/2020] [Accepted: 09/25/2020] [Indexed: 12/12/2022] Open
Abstract
Background/Aims We evaluated whether anti-Saccharomyces cerevisiae antibody (ASCA) titers are associated with diagnostic findings, disease activity, Paris classification phenotypes, and persistence after infliximab (IFX) treatment in children with Crohn’s disease (CD). We also investigated the role of ASCA as a predictor of mucosal healing (MH) and clinical remission (CR). Methods This study included 61 CD patients aged 19 years or younger who were diagnosed and treated between September 2010 and January 2019 and followed for at least 1 year. ASCA was regularly measured at the diagnosis of CD and at least 1 year after IFX therapy. Results The average follow-up period was 3.8±3.4 years (range, 1.0 to 7.2 years). Regression analysis showed that the ASCA titer was the only factor associated with Simple Endoscopic Score for Crohn's Disease (SES-CD) or CR among all the parameters. In patients who had achieved MH (SES-CD=0), ASCA immunoglobulin G (IgG) was not associated with MH, but in patients without MH, ASCA IgG was associated with SES-CD (p=0.005) and CR (p<0.001). The cutoff value of ASCA IgG in patients with CR was 21.8 units. However, there was no difference in the relapse rate between the ASCA IgG-positive and -negative groups during the follow-up period. Conclusions In patients who have not achieved MH, ASCA IgG is closely related to mucosal damage and CR. Unlike Western studies, ASCA IgG may be more helpful in predicting prognosis than immunoglobulin A in Korean patients, but it is not an appropriate indicator to predict the relapse of CD. (Gut Liver 2021;15-770)
Collapse
Affiliation(s)
- Mi Jin Kim
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eunsil Kim
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ben Kang
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Yoon Lee
- Department of Pediatrics, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Eun-Suk Kang
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yon Ho Choe
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|
|
5
|
Halligan S, Boone D, Archer L, Ahmad T, Bloom S, Rodriguez-Justo M, Taylor SA, Mallett S. Prognostic biomarkers to identify patients likely to develop severe Crohn's disease: a systematic review. Health Technol Assess 2021; 25:1-66. [PMID: 34225839 DOI: 10.3310/hta25450] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Identification of biomarkers that predict severe Crohn's disease is an urgent unmet research need, but existing research is piecemeal and haphazard. OBJECTIVE To identify biomarkers that are potentially able to predict the development of subsequent severe Crohn's disease. DESIGN This was a prognostic systematic review with meta-analysis reserved for those potential predictors with sufficient existing research (defined as five or more primary studies). DATA SOURCES PubMed and EMBASE searched from inception to 1 January 2016, updated to 1 January 2018. REVIEW METHODS Eligible studies were studies that compared biomarkers in patients who did or did not subsequently develop severe Crohn's disease. We excluded biomarkers that had insufficient research evidence. A clinician and two statisticians independently extracted data relating to predictors, severe disease definitions, event numbers and outcomes, including odds/hazard ratios. We assessed risk of bias. We searched for associations with subsequent severe disease rather than precise estimates of strength. A random-effects meta-analysis was performed separately for odds ratios. RESULTS In total, 29,950 abstracts yielded just 71 individual studies, reporting 56 non-overlapping cohorts. Five clinical biomarkers (Montreal behaviour, age, disease duration, disease location and smoking), two serological biomarkers (anti-Saccharomyces cerevisiae antibodies and anti-flagellin antibodies) and one genetic biomarker (nucleotide-binding oligomerisation domain-containing protein 2) displayed statistically significant prognostic potential. Overall, the strongest association with subsequent severe disease was identified for Montreal B2 and B3 categories (odds ratio 4.09 and 6.25, respectively). LIMITATIONS Definitions of severe disease varied widely, and some studies confounded diagnosis and prognosis. Risk of bias was rated as 'high' in 92% of studies overall. Some biomarkers that are used regularly in daily practice, for example C-reactive protein, were studied too infrequently for meta-analysis. CONCLUSIONS Research for individual biomarkers to predict severe Crohn's disease is scant, heterogeneous and at a high risk of bias. Despite a large amount of potential research, we encountered relatively few biomarkers with data sufficient for meta-analysis, identifying only eight biomarkers with potential predictive capability. FUTURE WORK We will use existing data sets to develop and then validate a predictive model based on the potential predictors identified by this systematic review. Contingent on the outcome of that research, a prospective external validation may prove clinically desirable. STUDY REGISTRATION This study is registered as PROSPERO CRD42016029363. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 45. See the NIHR Journals Library website for further project information.
Collapse
Affiliation(s)
- Steve Halligan
- Centre for Medical Imaging, University College London, London, UK
| | - Darren Boone
- Centre for Medical Imaging, University College London, London, UK
| | - Lucinda Archer
- Centre for Prognosis Research, School of Primary, Community and Social Care, Keele University, Keele, UK
| | - Tariq Ahmad
- Department of Gastroenterology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
| | - Stuart Bloom
- Department of Gastroenterology, University College Hospital, London, UK
| | | | - Stuart A Taylor
- Centre for Medical Imaging, University College London, London, UK
| | - Sue Mallett
- Centre for Medical Imaging, University College London, London, UK
| |
Collapse
|
|
6
|
In vitro diagnostics for the medical dermatologist. Part I: Autoimmune tests. J Am Acad Dermatol 2021; 85:287-298. [PMID: 33852926 DOI: 10.1016/j.jaad.2021.02.090] [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: 10/19/2020] [Revised: 02/10/2021] [Accepted: 02/24/2021] [Indexed: 11/24/2022]
Abstract
Despite the expansion of available in vitro laboratory tests at a rate far exceeding that of dermatologic pharmaceuticals, the existing literature is dominated by discussion of the latter. With the advent of numerous new tests, it can be difficult for practicing dermatologists to stay up-to-date on the available options, methodologies, and recommendations for when to order one test over another. Understanding the inherent strengths and weaknesses of these options is necessary to inform appropriate ordering and proper interpretation of the results. The first article in this continuing medical education series summarizes information on methodology, test characteristics, and limitations of several in vitro laboratory tests used for the work up of undifferentiated patients suspected of having dermatologic autoimmune diseases and it provides a general guide to ordering these tests.
Collapse
|
|
7
|
Choe YH. Precision medicine for pediatric inflammatory bowel disease: a perspective. PRECISION AND FUTURE MEDICINE 2020. [DOI: 10.23838/pfm.2020.00058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
|
|
8
|
Anti-Saccharomyces cerevisiae Antibodies as a Prognostic Biomarker in Children With Crohn Disease. J Pediatr Gastroenterol Nutr 2019; 69:82-87. [PMID: 30789863 DOI: 10.1097/mpg.0000000000002311] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVE Although anti-Saccharomyces cerevisiae antibodies (ASCAs) could be a useful biomarker in differentiating Crohn disease (CD) from ulcerative colitis (UC), their role as prognostic markers in children with CD has been underinvestigated. This longitudinal prospective observational study aimed to assess the prognostic value of ASCA status among children with CD managed using biologics. METHODS The study population comprised children with inflammatory bowel disease diagnosed with CD from 2012 to 2018. Cox regression model with adjustment for a priori covariates was used to examine the response to anti-tumor necrosis factor (TNF) biological therapy among ASCA-positive patients in comparison to ASCA-negative patients. RESULTS There were 273 measurements available from the study cohort comprising children with CD, who were followed up for a median duration of 14 months (interquartile range 5-42). ASCA-positive patients had a higher risk for moderate to severe clinical disease (odds ratio 2.88; 95% confidence interval [CI] 1.2-7.55) and extensive endoscopic distribution (odds ratio 3.30; CI 1.12-9.74) at baseline in comparison to ASCA-negative patients, respectively. In comparison to ASCA immunoglobulin G (IgG)-negative patients, ASCA IgG-positive patients who were treated with biologics had a significantly lower relapse rate (adjusted hazard ratio 0.12; CI 0.02-0.93). Ten (14%) patients had an unstable ASCA value with either ASCA immunoglobulin A or ASCA IgG status changing from positive to negative or vice versa. CONCLUSIONS ASCA-positive children with CD present with more extensive (endoscopic) and clinically severe disease. ASCA IgG is a useful prognostic marker among children with CD who receive biologics.
Collapse
|
|
9
|
Horn MP, Peter AM, Righini Grunder F, Leichtle AB, Spalinger J, Schibli S, Sokollik C. PR3-ANCA and panel diagnostics in pediatric inflammatory bowel disease to distinguish ulcerative colitis from Crohn's disease. PLoS One 2018; 13:e0208974. [PMID: 30557305 PMCID: PMC6296712 DOI: 10.1371/journal.pone.0208974] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 11/28/2018] [Indexed: 02/07/2023] Open
Abstract
Background Accurate classification of patients with inflammatory bowel disease into the subtypes ulcerative colitis (UC) and Crohn’s disease (CD) is still a challenge, but important for therapy and prognosis. Objectives To evaluate the diagnostic utility of anti-neutrophil cytoplasmic antibodies specific for proteinase-3 (PR3-ANCA) for ulcerative colitis (UC) and the value of an antibody panel incorporating PR3-ANCA to differentiate between Crohn’s disease (CD) and UC. Study design In this cohort study, 122 pediatric and adolescent individuals were retrospectively included (61 IBD patients of two clinical centers, 61 non-IBD controls). All subjects had a comprehensive antibody profile done from stored sera taken close to time of diagnosis. By employing quasi-exhaustive logistic regression the best discriminative model for UC and CD,subjects was determined in a training cohort and confirmed in a validation cohort. Results PR3-ANCA was specifically associated with UC (odds ratio (OR), 17.6; 95% confidence interval (CI); 3.6, 87); P < .001). A four antibody-panel including PR3-ANCA had an AUC of 90.81% (95%CI; 81.93, 99.69) to distinguish between UC and CD in the training cohort. In a smaller external validation cohort, the AUC was 84.13% (95%CI; 64.21, 100) for accurate diagnosis of CD and UC. Conclusion PR3-ANCA is highly specific for UC. The differentiating capability of a panel, which contains PR3-ANCA and weighs broadly available antibodies, is superior and utilization of the panel can support accurate classification in the work-up of pediatric and adolescent patients with IBD patients.
Collapse
Affiliation(s)
- Michael P. Horn
- University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Anna Maria Peter
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University Children‘s Hospital, Inselspital, University of Bern, Bern, Switzerland
| | - Franziska Righini Grunder
- Division of Pediatric Gastroenterology, Children's Hospital of Lucerne, Lucerne, Switzerland
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Sainte-Justine University Health Centre, Montreal, Canada
| | - Alexander B. Leichtle
- University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- IDSC–Insel Data Science Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Johannes Spalinger
- Division of Pediatric Gastroenterology, Children's Hospital of Lucerne, Lucerne, Switzerland
| | - Susanne Schibli
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University Children‘s Hospital, Inselspital, University of Bern, Bern, Switzerland
| | - Christiane Sokollik
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University Children‘s Hospital, Inselspital, University of Bern, Bern, Switzerland
- * E-mail:
| |
Collapse
|
|
10
|
Hamilton AL, Kamm MA, De Cruz P, Wright EK, Selvaraj F, Princen F, Gorelik A, Liew D, Lawrance IC, Andrews JM, Bampton PA, Sparrow MP, Florin TH, Gibson PR, Debinski H, Gearry RB, Macrae FA, Leong RW, Kronborg I, Radford-Smith G, Selby W, Bell SJ, Brown SJ, Connell WR. Serologic antibodies in relation to outcome in postoperative Crohn's disease. J Gastroenterol Hepatol 2017; 32:1195-1203. [PMID: 27976801 DOI: 10.1111/jgh.13677] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Revised: 11/21/2016] [Accepted: 12/11/2016] [Indexed: 01/02/2023]
Abstract
BACKGROUND AND AIM Disease recurs frequently after Crohn's disease resection. The role of serological antimicrobial antibodies in predicting recurrence or as a marker of recurrence has not been well defined. METHODS A total of 169 patients (523 samples) were prospectively studied, with testing peri-operatively, and 6, 12 and 18 months postoperatively. Colonoscopy was performed at 18 months postoperatively. Serologic antibody presence (perinuclear anti-neutrophil cytoplasmic antibody [pANCA], anti-Saccharomyces cerevisiae antibodies [ASCA] IgA/IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2, anti-Fla-X) and titer were tested. Quartile sum score (range 6-24), logistic regression analysis, and correlation with phenotype, smoking status, and endoscopic outcome were assessed. RESULTS Patients with ≥ 2 previous resections were more likely to be anti-OmpC positive (94% vs 55%, ≥ 2 vs < 2, P = 0.001). Recurrence at 18 months was associated with anti-Fla-X positivity at baseline (49% vs 29%; positive vs negative, P = 0.033) and 12 months (52% vs 31%, P = 0.04). Patients positive (n = 28) for all four antibacterial antibodies (anti-CBir1, anti-OmpC, anti-A4-Fla2, and anti-Fla-X) at baseline were more likely to experience recurrence at 18 months than patients negative (n = 32) for all four antibodies (82% vs 18%, P = 0.034; odds ratio 6.4, 95% confidence interval 1.16-34.9). The baseline quartile sum score for all six antimicrobial antibodies was higher in patients with severe recurrence (Rutgeert's i3-i4) at 18 months, adjusted for clinical risk factors (odds ratio 1.16, 95% confidence interval 1.01-1.34, P = 0.039). Smoking affected antibody status. CONCLUSIONS Anti-Fla-X and presence of all anti-bacterial antibodies identifies patients at higher risk of early postoperative Crohn's disease recurrence. Serologic screening pre-operatively may help identify patients at increased risk of recurrence.
Collapse
Affiliation(s)
- Amy L Hamilton
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Michael A Kamm
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Peter De Cruz
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.,Austin Health, Melbourne, Victoria, Australia
| | - Emily K Wright
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | | | - Fred Princen
- Prometheus Laboratories, San Diego, California, USA
| | - Alexandra Gorelik
- Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Victoria, Australia
| | - Danny Liew
- Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Victoria, Australia
| | - Ian C Lawrance
- School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.,Centre for Inflammatory Bowel Diseases, Saint John of God Hospital, Subiaco, Western Australia, Australia.,Harry Perkins Institute for Medical Research, Nedlands, Western Australia, Australia.,Fiona Stanley Hospital, Perth, Western Australia, Australia
| | - Jane M Andrews
- Department of Gastroenterology and Hepatology, University of Adelaide, Adelaide, South Australia, Australia.,Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Peter A Bampton
- Department of Gastroenterology and Hepatology, Flinders Medical Centre and Flinders University, Adelaide, South Australia, Australia
| | - Miles P Sparrow
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia
| | - Timothy H Florin
- Immunity Infection and Inflammation Program, Mater Research Institute-University of Queensland, and School of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Translational Research Institute, Woolloongabba, Queensland, Australia
| | - Peter R Gibson
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia.,Department of Gastroenterology, Monash University, Melbourne, Victoria, Australia
| | - Henry Debinski
- Melbourne Gastrointestinal Investigation Unit, Cabrini Hospital, Melbourne, Victoria, Australia
| | - Richard B Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Finlay A Macrae
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.,Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Rupert W Leong
- Gastroenterology and Liver Services, Concord and Bankstown Hospitals and University of New South Wales, Sydney, New South Wales, Australia
| | - Ian Kronborg
- Department of Gastroenterology, Western Hospital, Melbourne, Victoria, Australia
| | - Graham Radford-Smith
- Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.,IBD Group Queensland Institute of Medical Research, University of Queensland, Brisbane, Queensland, Australia
| | - Warwick Selby
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Sally J Bell
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.,Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Steven J Brown
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia
| | - William R Connell
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia
| |
Collapse
|
|
11
|
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.
Collapse
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
| |
Collapse
|
|
12
|
El-Matary W, Dupuis K, Sokoro A. Anti-Saccharomyces cerevisiae antibody titres correlate well with disease activity in children with Crohn's disease. Acta Paediatr 2015; 104:827-30. [PMID: 25877674 DOI: 10.1111/apa.13026] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2015] [Revised: 03/15/2015] [Accepted: 04/10/2015] [Indexed: 12/12/2022]
Abstract
AIM The role of noninvasive biologic markers for disease activity is very important in children with Crohn's disease. The aim of this study was to assess an association between disease activity and quantitative serum anti-Saccharomyces cerevisiae antibody (ASCA) titres. METHODS Anti-Saccharomyces cerevisiae antibody immunoglobulin (Ig) A and immunoglobulin G titres, paediatric Crohn's disease activity index (PCDAI), serum albumin and C-reactive protein (CRP) were repeatedly measured simultaneously in children with Crohn's disease. A possible association between ASCA IgA and IgG titres and changes in PCDAI was examined. RESULTS Serial 136 measurements of ASCA IgA and IgG titres were documented in 57 children with Crohn's disease over a mean duration of 3.1 ± 2.1 years. In a univariate linear regression model, there were significant correlations between ASCA IgA titres and PCDAI (p < 0.001), CRP (p <0.01) and low serum albumin (p < 0.001), respectively. Similarly, ASCA IgG titres significantly correlated with PCDAI, CRP and low serum albumin. CONCLUSION Both ASCA IgA and IgG titres seemed to correlate well with clinical Crohn's disease activity in children. Measuring these antibodies may be considered during routine clinical care for those patients.
Collapse
Affiliation(s)
- Wael El-Matary
- Section of Paediatric Gastroenterology; Departments of Paediatrics; Faculty of Medicine; University of Manitoba; Winnipeg MB Canada
- The Children's Hospital Research Institute of Manitoba; University of Manitoba; Winnipeg MB Canada
| | - Karine Dupuis
- Section of Paediatric Gastroenterology; Departments of Paediatrics; Faculty of Medicine; University of Manitoba; Winnipeg MB Canada
| | - AbdulRazaq Sokoro
- Internal Medicine and Pathology; Faculty of Medicine; University of Manitoba; Winnipeg MB Canada
| |
Collapse
|
|
13
|
O'Donnell S, Crotty PL, O'Sullivan M, Breslin N, O'Connor HJ, O'Morain CA, Ryan BM. Isolated active ileitis: is it a mild subtype of Crohn's disease? Inflamm Bowel Dis 2013; 19:1815-1822. [PMID: 23751397 DOI: 10.1097/mib.0b013e31828dc68b] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Ileal intubation is being increasingly performed at colonoscopy and has in turn lead to an increasingly recognized subgroup of patients-those with mild terminal ileal inflammation, an entity that we have coined isolated active ileitis (IAI). The aims of this study were to define the natural history of IAI and determine if IAI shares a similar genetic and serologic profile with Crohn's disease (CD). METHODS Patients with IAI were identified from our institution's histopathology and endoscopy databases. Cases attended for repeat colonoscopy and blood were analyzed for the expression of antineutrophil cytoplasmic antibody, anti-OmpC, anti-Saccharomyces cerevisiae antigen (ASCA) IgA, ASCA IgG, and anti-CBir antibodies and NOD2 genotyping. Age and sex-matched healthy controls, CD, and UC cases were also recruited. RESULTS Sixty-three patients with IAI were recruited. There was no significant difference in the prevalence of antibodies between IAI cases and healthy controls for antineutrophil cytoplasmic antibody, OmpC, ASCA IgA, or ASCA IgG. The presence of all 5 antibodies was significantly higher in the CD group than the IAI group, P < 0.05. There were 28.6% of CD cases that carried one or more NOD2 variants, compared to 26.2% of the IAI cohort and 6.1% of healthy controls. Forty-three cases underwent follow-up ileocolonoscopy. Six of 43 cases (14%) had definite CD. CONCLUSIONS A majority of IAI cases developed persistent symptoms and terminal ileal abnormalities; however, only 14% developed classical, histological, or radiological features of CD. Although patients with IAI have a low level of seropositivity, similar to healthy controls, they do share an excess of NOD2 mutations with CD cases.
Collapse
Affiliation(s)
- Sarah O'Donnell
- Department of Gastroenterology, AMNCH/Trinity College Dublin, Dublin, Ireland.
| | | | | | | | | | | | | |
Collapse
|
|
14
|
Prideaux L, De Cruz P, Ng SC, Kamm MA. Serological antibodies in inflammatory bowel disease: a systematic review. Inflamm Bowel Dis 2012; 18:1340-55. [PMID: 22069240 DOI: 10.1002/ibd.21903] [Citation(s) in RCA: 137] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2011] [Accepted: 08/25/2011] [Indexed: 12/13/2022]
Abstract
The diagnosis of inflammatory bowel disease (IBD) is traditionally based on a combination of clinical, endoscopic, histological, and radiological criteria. However, further testing is needed in cases of diagnostic uncertainty and in predicting disease course. This systematic review focuses on the potential for 10 serological antibodies to fill these roles: pANCA, ASCA, anti-OmpC, anti-CBir1, anti-I2, ALCA, ACCA, AMCA, anti-L, and anti-C. We discuss their prevalence in IBD and health; their role in disease diagnosis and risk stratification; their stability over time; their presence in unaffected relatives; their association with genetic variants; and differences across ethnic groups. Serological antibodies have some role in primary diagnosis and in differentiating between Crohn's disease and ulcerative colitis. In indeterminate colitis, preoperative measurement of serological antibodies can help to predict the likelihood of complications among patients undergoing pouch surgery. The combined presence and magnitude of a large panel of antibodies appear to be of value in predicting disease progression. There is currently insufficient evidence to recommend the use of antibody testing to predict responses to treatment or surgery in patients with IBD.
Collapse
Affiliation(s)
- Lani Prideaux
- Department of Gastroenterology, St Vincent's Hospital Melbourne, Australia
| | | | | | | |
Collapse
|
|
15
|
Abstract
The search for the underlying trigger of an inappropriate inflammatory reaction characteristic of inflammatory bowel diseases (IBD) has led to the discovery of several antibodies. The panel of serologic markers for IBD is rapidly expanding. Serologic markers hold the promise of helping researchers and clinicians to better understand IBD heterogeneity and natural history. The real importance of the antibodies produced against various microbial and autoantigens is still uncertain. Whether these antibodies play a primary role in the pathogenesis of IBD, or their presence is only a consequence of the inflamed mucosa is a fundamental question that remains to be clarified. The impact of the routine evaluation of these serologic markers in the everyday clinical IBD diagnostic algorithm is questionable due to their limited sensitivity. Despite their great potential, the routine use of serologic markers for diagnosis and follow-up is currently not justified. However, their correlation with disease phenotype and behavior is more established. A combination of serum markers has been shown to be of more value compared to using single markers alone. The ongoing challenge is how to best utilize these serologic markers to provide clinically relevant information in a cost-effective manner. Further prospective clinical trials are needed to determine their exact role in pathogenesis and practical clinical importance. We review the current standpoint of the clinical impact of various established and newly suggested markers in Crohn's disease and ulcerative colitis.
Collapse
Affiliation(s)
- László Herszényi
- Second Department of Medicine, Semmelweis University, Budapest, Hungary.
| | | |
Collapse
|
|
16
|
Petersen AM, Schou C, Mirsepasi H, Engberg J, Friis-Møller A, Nordgaard-Lassen I, Wildt S, Krogfelt KA. Seroreactivity to E. coli outer membrane protein C antibodies in active inflammatory bowel disease; diagnostic value and correlation with phylogroup B2 E. coli infection. Scand J Gastroenterol 2012; 47:155-61. [PMID: 22150030 DOI: 10.3109/00365521.2011.639080] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Several serologic tests, including anti-outer membrane porin C antibody (Omp C), are used for screening and as marker of disease course in inflammatory bowel diseases (IBD). Our aim was to investigate possible differences in Omp C level in patients with active and inactive IBD compared to controls. METHODS All blood samples were tested for Omp C. Disease activity was evaluated by Harvey Bradshaw Index, Simple Clinical Activity Index and Modified Pouchitis Disease Activity Index. RESULTS Blood samples were collected from 113 patients and 60 controls. Patients with active IBD did not have a higher level of Omp C than patients in remission. Surprisingly, in patients with active Crohn's disease a significantly lower level of Omp C was found compared with patients with inactive Crohn's disease (p < 0.05). All other groups among patients with IBD did have a significantly higher level of Omp C, compared with controls, including patients with acute gastroenteritis (p < 0.05). Although IBD patients with phylogroup B2 E. coli cultured from their fecal samples, were more likely to have a positive Omp C test (p < 0.05), this could not explain the low Omp C level in the subgroup of patients with active Crohn's disease. CONCLUSIONS Omp C titer was not raised in patients with active IBD compared with patients in remission. In addition, there was no difference in Omp C level in patients with active Crohn's disease compared with controls. These observations do not support the use of Omp C serology testing, either in disease activity assessment, or in screening for active Crohn's disease.
Collapse
Affiliation(s)
- Andreas Munk Petersen
- Department of Microbiological Surveillance and Research, Statens Serum Institut, Unit of Gastrointestinal and Serological Research, Copenhagen, Denmark.
| | | | | | | | | | | | | | | |
Collapse
|
|
17
|
Eser A, Papay P, Primas C, Pernicka E, Harrer M, Dejaco C, Novacek G, Lichtenberger C, Angelberger S, Kazemi L, Mikulits A, Vogelsang H, Reinisch W. The impact of intestinal resection on serum levels of anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with Crohn's disease. Aliment Pharmacol Ther 2012; 35:292-9. [PMID: 22146122 DOI: 10.1111/j.1365-2036.2011.04932.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Antibodies to Saccharomyces cerevisiae (ASCA) are highly prevalent in sera of patients with Crohn's disease and have been proposed to identify subgroups of patients with a disabling disease course. AIM To investigate the impact of intestinal resection on serum levels of ASCA in patients with Crohn's disease and the predictive value of ASCA levels on surgical recurrence. METHODS Sera from 60 patients who underwent 'curative' intestinal resection due to stricturing and/or penetrating complications were collected preoperatively and during post-operative follow-up (week 2, months 4, 8 and 11 ± 1). Measurement of ASCA IgG and IgA isotypes were performed using ELISA. Re-operation rate was associated with ASCA status and serum levels. RESULTS At baseline 44/60 (73%) of patients were rated as positive for ASCA IgG, 45/60 (75%) for ASCA IgA and 52/60 (87%) as positive for at least one of both. ASCA serum levels remained stable during first year from resection. After a median of 106 months 10 of 40 (25%) patients with long-term follow-up underwent one or more intestinal re-operations. Neither ASCA positivity nor absolute ASCA serum levels were predictive of surgical recurrence. CONCLUSIONS Serum ASCA levels remain stable after curative intestinal resection in Crohn's disease. This indicates the persistence of both stimulus and immunological mechanism operative in the production of ASCA even after complete surgical resection of macroscopically inflamed intestinal tissue. After intestinal resection, neither ASCA positivity nor ASCA serum levels predict the risk of surgical recurrence during long-term follow-up.
Collapse
Affiliation(s)
- A Eser
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Austria
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
18
|
Daperno M, Castiglione F, de Ridder L, Dotan I, Färkkilä M, Florholmen J, Fraser G, Fries W, Hebuterne X, Lakatos PL, Panés J, Rimola J, Louis E. Results of the 2nd part Scientific Workshop of the ECCO. II: Measures and markers of prediction to achieve, detect, and monitor intestinal healing in inflammatory bowel disease. J Crohns Colitis 2011; 5:484-498. [PMID: 21939926 DOI: 10.1016/j.crohns.2011.07.003] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2011] [Accepted: 07/08/2011] [Indexed: 12/13/2022]
Abstract
The healing of the intestine is becoming an important objective in the management of inflammatory bowel diseases. It is associated with improved disease outcome. Therefore the assessment of this healing both in clinical studies and routine practice is a key issue. Endoscopy for the colon and terminal ileum and computerized tomography or magnetic resonance imaging for the small bowel are the most direct ways to evaluate intestinal healing. However, there are many unsolved questions about the definition and the precise assessment of intestinal healing using these endoscopic and imaging techniques. Furthermore, these are relatively invasive and expensive procedures that may be inadequate for regular patients' monitoring. Therefore, biomarkers such as C-reactive protein and fecal calprotectin have been proposed as surrogate markers for intestinal healing. Nevertheless, the sensitivity and specificity of these markers for the prediction of healing may be insufficient for routine practice. New stool, blood or intestinal biomarkers are currently studied and may improve our ability to monitor intestinal healing in the future.
Collapse
Affiliation(s)
- Marco Daperno
- Gastroenterology Division, AO Ordine Mauriziano, Torino, Italy
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
19
|
Abstract
OBJECTIVE The gold standard for the diagnosis and evaluation of Crohn disease (CD) is endoscopy/colonoscopy, although this is invasive, costly, and associated with risks to the patient. Recently, circulating microRNAs (miRNAs) have emerged as promising noninvasive biomarkers. Here, we examined the utility of serum miRNAs as biomarkers of CD in children. PATIENTS AND METHODS Studies were conducted using sera samples from patients with pediatric CD, healthy controls, and a comparison group of patients with pediatric celiac disease. Serum miRNA levels were explored initially using a microfluidic quantitative reverse transcription-polymerase chain reaction array platform. Findings were subsequently validated using quantitative reverse transcription-polymerase chain reaction in larger validation sample sets. The diagnostic utility of CD-associated serum miRNA was examined using receiver operating characteristic analysis. RESULTS A survey of miRNA levels in the sera of control and patients with CD detected significant elevation of 24 miRNAs, 11 of which were chosen for further validation. All of the candidate biomarker miRNAs were confirmed in an independent CD sample set (n = 46). To explore the specificity of the CD-associated miRNAs, they were measured in the sera of patients with celiac disease (n = 12); none were changed compared with healthy controls. Receiver operating characteristic analyses revealed that serum miRNAs have promising diagnostic utility, with sensitivities for CD above 80%. Significant decreases in serum miRNAs were observed in 24 incident patients with pediatric CD after 6 months of treatment. CONCLUSIONS The present study identifies 11 CD-associated serum miRNA with encouraging diagnostic potential. Our findings suggest serum miRNAs may prove useful as noninvasive biomarkers in CD.
Collapse
|
|
20
|
Abstract
OBJECTIVE The gold standard for the diagnosis and evaluation of Crohn disease (CD) is endoscopy/colonoscopy, although this is invasive, costly, and associated with risks to the patient. Recently, circulating microRNAs (miRNAs) have emerged as promising noninvasive biomarkers. Here, we examined the utility of serum miRNAs as biomarkers of CD in children. PATIENTS AND METHODS Studies were conducted using sera samples from patients with pediatric CD, healthy controls, and a comparison group of patients with pediatric celiac disease. Serum miRNA levels were explored initially using a microfluidic quantitative reverse transcription-polymerase chain reaction array platform. Findings were subsequently validated using quantitative reverse transcription-polymerase chain reaction in larger validation sample sets. The diagnostic utility of CD-associated serum miRNA was examined using receiver operating characteristic analysis. RESULTS A survey of miRNA levels in the sera of control and patients with CD detected significant elevation of 24 miRNAs, 11 of which were chosen for further validation. All of the candidate biomarker miRNAs were confirmed in an independent CD sample set (n = 46). To explore the specificity of the CD-associated miRNAs, they were measured in the sera of patients with celiac disease (n = 12); none were changed compared with healthy controls. Receiver operating characteristic analyses revealed that serum miRNAs have promising diagnostic utility, with sensitivities for CD above 80%. Significant decreases in serum miRNAs were observed in 24 incident patients with pediatric CD after 6 months of treatment. CONCLUSIONS The present study identifies 11 CD-associated serum miRNA with encouraging diagnostic potential. Our findings suggest serum miRNAs may prove useful as noninvasive biomarkers in CD.
Collapse
|
|
21
|
Rieder F, Lopez R, Franke A, Wolf A, Schleder S, Dirmeier A, Schirbel A, Rosenstiel P, Dotan N, Schreiber S, Rogler G, Klebl F. Characterization of changes in serum anti-glycan antibodies in Crohn's disease--a longitudinal analysis. PLoS One 2011; 6:e18172. [PMID: 21573154 PMCID: PMC3089599 DOI: 10.1371/journal.pone.0018172] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2010] [Accepted: 02/27/2011] [Indexed: 12/20/2022] Open
Abstract
Introduction Anti-glycan antibodies are a promising tool for differential diagnosis and disease stratification of patients with Crohn's disease (CD). We longitudinally assessed level and status changes of anti-glycan antibodies over time in individual CD patients as well as determinants of this phenomenon. Methods 859 serum samples derived from a cohort of 253 inflammatory bowel disease (IBD) patients (207 CD, 46 ulcerative colitis (UC)) were tested for the presence of anti-laminarin (Anti-L), anti-chitin (Anti-C), anti-chitobioside (ACCA), anti-laminaribioside (ALCA), anti-mannobioside (AMCA) and anti-Saccharomyces cerevisiae (gASCA) antibodies by ELISA. All patients had at least two and up to eleven serum samples taken during the disease course. Results Median follow-up time for CD was 17.4 months (Interquartile range (IQR) 8.0, 31.6 months) and for UC 10.9 months (IQR 4.9, 21.0 months). In a subgroup of CD subjects marked changes in the overall immune response (quartile sum score) and levels of individual markers were observed over time. The marker status (positive versus negative) remained widely stable. Neither clinical phenotype nor NOD2 genotype was associated with the observed fluctuations. In a longitudinal analysis neither changes in disease activity nor CD behavior led to alterations in the levels of the glycan markers. The ability of the panel to discriminate CD from UC or its association with CD phenotypes remained stable during follow-up. In the serum of UC patients neither significant level nor status changes were observed. Conclusions While the levels of anti-glycan antibodies fluctuate in a subgroup of CD patients the antibody status is widely stable over time.
Collapse
Affiliation(s)
- Florian Rieder
- Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
22
|
Abstract
At diagnosis, the clinical presentation of both entities of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), can be highly heterogeneous, leading to a delay in correct identification or differentiation between CD and UC in a subgroup of patients. In addition, the natural history of IBD patients is strikingly variable. During the life of a CD patient, in the majority of instances, stricturing or perforating complications occur, leading to surgery. Serologic antiglycan antibodies directed against various microbial carbohydrate epitopes are useful in differentiation of CD vs. UC and are a promising tool for identification of CD patients at risk for rapid progression and need for surgical intervention. Instruments for prediction of CD behavior are critical, as the use of immunomodulators and/or biologicals early in the disease course might be justified for patients with a high hazard for complicated disease behavior.
Collapse
|
|
23
|
Rieder F, Schleder S, Wolf A, Dirmeier A, Strauch U, Obermeier F, Lopez R, Spector L, Fire E, Yarden J, Rogler G, Dotan N, Klebl F. Serum anti-glycan antibodies predict complicated Crohn's disease behavior: a cohort study. Inflamm Bowel Dis 2010; 16:1367-75. [PMID: 20024902 DOI: 10.1002/ibd.21179] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND A high proportion of patients with Crohn's disease (CD) over time develop complications like fistulae and strictures, requiring surgery. We tested a panel of antiglycan antibodies for predicting the occurrence of complications and CD-related surgery in an adult patient cohort. METHODS Serum samples of 149 CD patients of the German inflammatory bowel disease (IBD) network were tested for the presence of anti-laminarin IgA (Anti-L), anti-chitin IgA (Anti-C), anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-mannobioside IgG (AMCA), and anti-Saccaromyces cerevisiae IgG (gASCA) carbohydrate antibodies by enzyme-linked immunosorbent assay (ELISA) (IBDX(R) panel, Glycominds, Lod, Israel) in a blinded fashion. Clinical data were available on occurrence of complicated disease or CD-related surgery as well as disease activity, onset, and location. RESULTS The median follow-up of the patients without any previous complication or surgery at time of sample procurement was 53.7 months. Overall, 26.3% developed a complication and 17.1% underwent CD-related surgery, respectively. Positivity for gASCA, AMCA, ACCA, and Anti-L alone or an increasing frequency of positive serum antibodies independently predicted a faster progression toward a more severe disease course. Once a complication or surgery had occurred only positivity for Anti-L or more than 3 markers out of the whole panel indicated progression to an additional surgery or complication. The antibody status of most patients remained stable over time. CONCLUSIONS This is the first study showing the clinical value of serum antiglycan antibodies for prediction of a more complicated disease course in adult patients with CD.
Collapse
Affiliation(s)
- Florian Rieder
- Department of Internal Medicine I, University of Regensburg, Regensburg, Germany.
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
24
|
Standaert-Vitse A, Sendid B, Joossens M, François N, Vandewalle-El Khoury P, Branche J, Van Kruiningen H, Jouault T, Rutgeerts P, Gower-Rousseau C, Libersa C, Neut C, Broly F, Chamaillard M, Vermeire S, Poulain D, Colombel JF. Candida albicans colonization and ASCA in familial Crohn's disease. Am J Gastroenterol 2009; 104:1745-53. [PMID: 19471251 DOI: 10.1038/ajg.2009.225] [Citation(s) in RCA: 163] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Anti-Saccharomyces cerevisiae antibodies (ASCAs) are present in 50-60% of patients with Crohn's disease (CD) and in 20-25% of their healthy relatives (HRs). The yeast, Candida albicans, has been shown to generate ASCAs, but the presence of C. albicans in the digestive tract of CD patients and their HRs has never been investigated. Therefore, we studied C. albicans carriage in familial CD and its correlation with ASCAs. METHODS Study groups consisted of 41 CD families composed of 129 patients and 113 HRs, and 14 control families composed of 76 individuals. Mouth swabs and stool specimens were collected for isolation, identification, and quantification of yeasts. Serum samples were collected for detection of ASCAs and anti-C. albicans mannan antibodies (ACMAs). RESULTS C. albicans was isolated significantly more frequently from stool samples from CD patients (44%) and their HRs (38%) than from controls (22%) (P<0.05). The prevalence of ACMAs was similar between CD patients, their HRs, and controls (22, 19, and 21%, respectively, P=0.845), whereas the prevalence of ASCAs was significantly increased in CD families (72 and 34% in CD and HRs, respectively, in contrast to 4% in controls, P<0.0001). AMCA levels correlated with C. albicans colonization in all populations. ASCA levels correlated with C. albicans colonization in HRs but not in CD patients. CONCLUSIONS CD patients and their first-degree HRs are more frequently and more heavily colonized by C. albicans than are controls. ASCAs correlate with C. albicans colonization in HRs but not in CD. In HRs, ASCAs could result from an altered immune response to C. albicans. In CD, a subsequent alteration in sensing C. albicans colonization could occur with disease onset.
Collapse
Affiliation(s)
- Annie Standaert-Vitse
- INSERM, U799, Faculté de Médecine, Pôle Recherche, Université de Lille 2, Lille, France
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
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: 78] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
|
|
26
|
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.
Collapse
|
|
27
|
Papp M, Altorjay I, Dotan N, Palatka K, Foldi I, Tumpek J, Sipka S, Udvardy M, Dinya T, Lakatos L, Kovacs A, Molnar T, Tulassay Z, Miheller P, Norman GL, Szamosi T, Papp J, Lakatos PL. New serological markers for inflammatory bowel disease are associated with earlier age at onset, complicated disease behavior, risk for surgery, and NOD2/CARD15 genotype in a Hungarian IBD cohort. Am J Gastroenterol 2008; 103:665-681. [PMID: 18047543 DOI: 10.1111/j.1572-0241.2007.01652.x] [Citation(s) in RCA: 102] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Antibodies to Saccharomyces cerevisiae (S. cerevisiae) (ASCA) and porin protein-C of Escherichia coli (anti-OmpC) are associated with disease phenotype and may be of diagnostic importance in inflammatory bowel diseases (IBD). Our aim was to determine whether a panel of new antibodies against bacterial proteins and carbohydrates could help differentiate among the various forms of IBD, and whether they were associated with particular clinical manifestations in a Hungarian cohort of IBD patients. METHODS Six hundred fifty-two well-characterized, unrelated, consecutive IBD patients (CD [Crohn's disease] 557, men/women 262/295, duration 8.1 +/- 11.3 yr; ulcerative colitis [UC] 95, men/women 44/51, duration 8.9 +/- 9.8 yr) and 100 healthy and 48 non-IBD gastrointestinal (GI) controls were investigated. Sera were assayed for anti-OmpC and antibodies against a mannan epitope of S. cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by reviewing the patients' medical charts. RESULTS Sixty-six percent of the CD patients had at least one of the investigated antibodies. Among glycan antibodies, gASCA or the combination of gASCA and atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) was most accurate for differentiating between CD and UC. ASCA and gASCA assays performed similarly. Increasing amount and level of antibody responses toward gASCA, ALCA, ACCA, AMCA, and OmpC were associated with more complicated disease behavior (P < 0.0001) and need for surgery in CD (P= 0.023). A serological dosage effect was also observed. gASCA and AMCA antibodies were associated with NOD2/CARD15, in addition to a gene-dosage effect. No serotype-phenotype associations were found in UC. CONCLUSIONS Antibody response to this new panel of serological markers was associated with complicated disease phenotype, NOD2/CARD15 genotype, and a need for surgery in this eastern European IBD cohort.
Collapse
Affiliation(s)
- Maria Papp
- 2nd Department of Medicine, University of Debrecen, Debrecen, Hungary
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
28
|
Peyrin-Biroulet L, Standaert-Vitse A, Branche J, Chamaillard M. IBD serological panels: facts and perspectives. Inflamm Bowel Dis 2007; 13:1561-6. [PMID: 17636565 DOI: 10.1002/ibd.20226] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Beyond a defective innate immune response in inflammatory bowel disease (IBD), an increased immunological response toward microbial and self antigens has been intrinsically linked to the pathogenesis of such common immunopathologies of the gut. Mounting evidence indicates that increased seroreactivity toward certain antigens are a predictive and quantitative heritable trait, including the anti-Saccharomyces cerevisiae antibody (ASCA). Consistently, Candida albicans and Crohn's disease-associated NOD2 mutations have been recently identified as immunogen and genetic determinants for ASCA, respectively. In clinical practice, current panels of serological markers are not recommended for diagnosis, stratifying, and monitoring IBD. Therefore, prospective studies and highly sensitive serological panels of markers are eagerly awaited before guiding clinical decisions. Better understanding of the serological response in IBD might also provide new insights into their epidemiology and pathophysiology.
Collapse
|
|
29
|
Papp M, Altorjay I, Norman GL, Shums Z, Palatka K, Vitalis Z, Foldi I, Lakos G, Tumpek J, Udvardy ML, Harsfalvi J, Fischer S, Lakatos L, Kovacs A, Bene L, Molnar T, Tulassay Z, Miheller P, Veres G, Papp J, Lakatos PL. Seroreactivity to microbial components in Crohn's disease is associated with ileal involvement, noninflammatory disease behavior and NOD2/CARD15 genotype, but not with risk for surgery in a Hungarian cohort of IBD patients. Inflamm Bowel Dis 2007; 13:984-992. [PMID: 17417801 DOI: 10.1002/ibd.20146] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Antibodies directed against Saccharomyces cerevisiae (ASCA), perinuclear components of neutrophils (pANCA), and porin protein C of Escherichia coli (anti-OmpC) are reported to be associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Since limited data are available from Eastern Europe, we assessed the above antibodies in Hungarian IBD patients. METHODS In all, 653 well-characterized, unrelated consecutive IBD patients (Crohn's disease [CD]: 558, m/f: 263/295, duration: 8.1 +/- 10.7 years; ulcerative colitis [UC]: 95, m/f: 44/51, duration: 8.9 +/- 9.8 years) and 100 healthy subjects were investigated. Sera were assayed for anti-Omp and ASCA by enzyme-linked immunosorbent assay (ELISA) and ANCA by indirect immunofluorescence assay (IIF). TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS Anti-Omp, ASCA, and atypical pANCA antibodies were present in 31.2%, 59.3%, and 13.8% of CD, 24.2%, 13.7%, and 48.5% of UC patients, and in 20%, 16%, and 5.6% of controls, respectively. ASCA and anti-Omp positivity were associated with increased risk for CD (odds ratio [OR](ASCA) = 7.65, 95% confidence interval [CI]: 4.37-13.4; OR(Omp) = 1.81, 95% CI: 1.08-3.05). In a logistic regression analysis, anti-Omp and ASCA were independently associated with ileal and noninflammatory disease, but not with a risk for surgery or response to steroids or infliximab. A serology dosage effect was also observed. ASCA and anti-Omp antibodies were associated with NOD2/CARD15, in addition to a gene dosage effect. No associations were found in UC. CONCLUSIONS Serological markers were useful in the differentiation between CD and UC in an Eastern European IBD cohort. Reactivity to microbial components was associated with disease phenotype and NOD2/CARD15 genotype, further supporting the role of altered microbial sensing in the pathogenesis of CD.
Collapse
Affiliation(s)
- Maria Papp
- 2nd Department of Medicine, University of Debrecen, Debrecen, Hungary
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Odes S, Friger M, Vardi H, Claessens G, Bossuyt X, Riis L, Munkholm P, Wolters F, Yona H, Hoie O, Beltrami M, Tsianos E, Katsanos K, Mouzas I, Clofent J, Monteiro E, Messori A, Politi P, O'Morain C, Limonard C, Russel M, Vatn M, Moum B, Stockbrugger R, Vermeire S. Role of ASCA and the NOD2/CARD15 mutation Gly908Arg in predicting increased surgical costs in Crohn's disease patients: a project of the European Collaborative Study Group on Inflammatory Bowel Disease. Inflamm Bowel Dis 2007; 13:874-881. [PMID: 17278126 DOI: 10.1002/ibd.20122] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
BACKGROUND NOD2/CARD15, the first identified susceptibility gene in Crohn's disease (CD), is associated with ileal stenosis and increased frequency of surgery. Anti-Saccharomyces cerevisiae antibody (ASCA), a serological marker for CD, is associated with ileal location and a high likelihood for surgery. We hypothesized that the presence of ASCA and NOD2/CARD15 mutations could predict increased health care cost in CD. METHODS CD patients in a prospectively designed community-based multinational European and Israeli cohort (n = 228) followed for mean 8.3 (SD 2.6) years had blood drawn for measurement of ASCA (IgG, IgA), Arg702Trp, Gly908Arg, and Leu1007fsinsC. Days spent in the hospital and the costs of medical and surgical hospitalizations and medications were calculated. RESULTS The median duration of surgical hospitalizations was longer in Gly908Arg-positive than -negative patients, 3.5 and 1.5 days/patient-year (P < 0.01), and in ASCA-positive than -negative patients, 1.1 and 0 days/patient-year (P < 0.001). Median surgical hospitalization cost was 1,580 euro/patient-year in Gly908Arg-positive versus 0 euro/patient-year in -negative patients (P < 0.01), and 663 euro/patient-year in ASCA-positive versus 0 euro/patient-year in -negative patients (P < 0.001). Differences in cost of medications between groups were not significant. The effect of Gly908Arg was expressed in countries with higher Gly908Arg carriage rates. ASCA raised surgical costs independently of the age at diagnosis of disease. Arg702Trp and Leu1007fsinsC did not affect the cost of health care. CONCLUSIONS Since CD patients positive for Gly908Arg and ASCA demonstrated higher health care costs, it is possible that measurement of Gly908Arg and ASCA at disease diagnosis can forecast the expensive CD patients.
Collapse
Affiliation(s)
- Shmuel Odes
- Gastroenterology and Hepatology Department, Soroka Hospital and Ben Gurion University of Negev, Beer Sheva, Israel.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
31
|
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.
Collapse
Affiliation(s)
- Mária Papp
- Debreceni Egyetem, Orvos- és Egészségtudományi Centrum Belgyógyászati Intézet, Gasztroenterológiai Tanszék, Debrecen.
| | | | | |
Collapse
|
|
32
|
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.
Collapse
|
|
33
|
Müller S, Styner M, Seibold-Schmid B, Flogerzi B, Mähler M, Konrad A, Seibold F. Anti-Saccharomyces cerevisiae antibody titers are stable over time in Crohn's patients and are not inducible in murine models of colitis. World J Gastroenterol 2006; 11:6988-94. [PMID: 16437604 PMCID: PMC4717042 DOI: 10.3748/wjg.v11.i44.6988] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate ASCA production over time in CD and murine colitis in order to further our understanding of their etiology. MATERIALS AND METHODS Sixty-six CD patients were compared to ulcerative colitis (UC) and irritable bowel syndrome patients with respect to ASCA production as measured by ELISA. ASCA IgG or IgA positivity as well as change in titers over a period of up to 3 years (Delta IgG/A) was correlated with clinical parameters such as CD activity index (CDAI) and C-reactive protein levels (CRP). Moreover, two murine models of colitis (DSS and IL-10 knock out) were compared to control animals with respect to ASCA titers after oral yeast exposure. RESULTS ASCA IgG and IgA titers are stable over time in CD and non-CD patients. Fistular disease was associated with a higher rate of ASCA IgA positivity (P = 0.014). Ileal disease was found to have a significant influence on the Delta IgG of ASCA (P = 0.032). There was no correlation found between ASCA positivity or Delta IgG/A and clinical parameters of CD: CDAI and CRP. In mice, neither healthy animals nor animals with DSS-induced or spontaneous colitis exhibited a marked increase in ASCA titers after high-dose yeast exposure. On the other hand, mice immunized intraperitoneally with mannan plus adjuvant showed a marked and significant increase in ASCA titers compared to adjuvant-only immunized controls (P = 0.014). CONCLUSION The propensity to produce ASCA in a subgroup of CD patients is largely genetically predetermined as evidenced by their stability and lack of correlation with clinical disease activity parameters. Furthermore, in animal models of colitis, mere oral exposure of mice to yeast does not lead to the induction of marked ASCA titers irrespective of concomitant colonic inflammation. Hence, environment may play only a minor role in inducing ASCA.
Collapse
Affiliation(s)
- Stefan Müller
- Division of Gastroenterology, Department of Clinical Research, University Hospital Bern.
| | | | | | | | | | | | | |
Collapse
|
|
34
|
Mallant-Hent RC, Mooij M, von Blomberg BM, Linskens RK, van Bodegraven AA, Savelkoul PH. Correlation between Saccharomyces cerevisiae DNA in intestinal mucosal samples and anti- Saccharomyces cerevisiae antibodies in serum of patients with IBD. World J Gastroenterol 2006; 12:292-7. [PMID: 16482632 PMCID: PMC4066041 DOI: 10.3748/wjg.v12.i2.292] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the correlation between ASCA and presence of mucosal S. cerevisiae DNA in a population of CD, ulcerative colitis (UC) patients and controls.
METHODS: S. cerevisiae-specific primers and a fluorescent probe were designed for a 5’ exonuclease real time PCR (TaqManTM) assay, which is a homogenous system using a fluorescent-labelled probe for the detection of PCR product in real time. We analyzed the relation of the PCR results with the ASCA findings in a group of 76 inflammatory bowel disease (IBD) patients (31 CD, 45 UC) and 22 healthy controls (HC).
RESULTS: ASCA (IgA or IgG) were positive in 19 (61%) patients with CD, 12 (27%) with UC and none of the HC. PCR amplification was inhibited and excluded from the final results in 10 (22%) UC patients, 7 (22%) CD patients, and 6 (30%) HC. In only 15 of the mucosal samples, S. cerevisiae DNA was detected by real time PCR, including 7 (29%) in CD, 7 (19%) in UC, 1 (6%) in HC. In 4 CD and in 4 UC patients, ASCA and mucosal S. cerevisiae were positive. Mucosal S. cerevisiae was present in combination with negative ASCA IgA and IgG in 3 UC, and 3 CD patients.
CONCLUSION: We conclude that since the presence of S. cerevisiae in colonic mucosal biopsy specimens is very rare, ASCA is unlikely to be explained by continuous exposure to S. cerevisiae in the mucosa. Therefore, ASCA formation must occur earlier in life and levels remain relatively stable thereafter in immunological susceptible persons.
Collapse
Affiliation(s)
- R-C Mallant-Hent
- Department of Gastroenterology, VU University Medical Center, Postbox 7057, 1007 MB Amsterdam, The Netherlands
| | | | | | | | | | | |
Collapse
|
|
35
|
Granito A, Zauli D, Muratori P, Muratori L, Grassi A, Bortolotti R, Petrolini N, Veronesi L, Gionchetti P, Bianchi FB, Volta U. Anti-Saccharomyces cerevisiae and perinuclear anti-neutrophil cytoplasmic antibodies in coeliac disease before and after gluten-free diet. Aliment Pharmacol Ther 2005; 21:881-887. [PMID: 15801923 DOI: 10.1111/j.1365-2036.2005.02417.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Anti-Saccharomyces cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies are markers of Crohn's disease and ulcerative colitis respectively. AIM To determine the prevalence of anti-S. cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies in a large series of coeliac disease patients before and after gluten free diet, and to correlate anti-S. cerevisiae-positivity with intestinal mucosal damage. METHODS One hundred and five consecutive coeliac disease patients and 141 controls (22 ulcerative colitis, 24 Crohn's disease, 30 primary sclerosing cholangitis, 15 postenteritis syndrome, 50 blood donors) were tested for anti-S. cerevisiae by enzyme-linked immunosorbent assay and for perinuclear anti-neutrophil cytoplasmic autoantibodies by indirect immunofluorescence. RESULTS In coeliac disease anti-S. cerevisiae (immunoglobulin G and/or immunoglobulin A) were slightly less frequent (59%) than in Crohn's disease (75%, P = 0.16) and significantly more frequent than in ulcerative colitis (27%), primary sclerosing cholangitis (30%), postenteritis syndrome (26%) and blood donors (4%) (P = 0.009, P = 0.0002, P = 0.025, P < 0.0001). No correlation was found between anti-S. cerevisiae and degree of mucosal damage. Perinuclear anti-neutrophil cytoplasmic autoantibodies were detected only in one coeliac. After gluten free diet the disappearance of anti-S. cerevisiae-immunoglobulin A (93%) was more frequent than that of immunoglobulin G (17%, P = 0.0001); perinuclear anti-neutrophil cytoplasmic autoantibodies disappeared in the only coeliac positive at diagnosis. CONCLUSION More than half of untreated coeliacs are anti-S. cerevisiae-positive irrespective of the severity of mucosal damage. Differently from immunoglobulin A, anti-S. cerevisiae-immunoglobulin G persisted in more than 80% after gluten free diet. The high prevalence of anti-S. cerevisiae in coeliac disease suggests that they may be the effect of a non-specific immune response in course of chronic small bowel disease.
Collapse
Affiliation(s)
- A Granito
- Department of Internal Medicine, Alma Mater Studiorum, University of Bologna, Policlinico Sant'Orsola-Malpighi, 40138 Bologna, Italy.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Abstract
The natural history of Crohn disease is characterized by recurrent bouts of active disease, the consequences of which can severely impair sufferers' physical and social functioning. Not only does the illness cause day-to-day morbidity for children but the consequence of the chronic inflammatory process also commonly results in the need for major intestinal surgery. The present challenge facing physicians treating children with Crohn disease is to alleviate symptoms and prolong periods of remission via the use of specifically targeted therapies while minimizing toxicity and promoting normal growth and development. Although systemic corticosteroids are effective in inducing clinical remission, they are of little or no benefit in maintaining remission and can contribute to linear growth retardation. Immunomodulating drugs such as azathioprine, 6-mercaptopurine and methotrexate have proved effective for inducing and maintaining remission of active Crohn disease. These agents are now commonly prescribed in children at diagnosis, after a severe attack or after surgery or in those who become corticosteroid-dependent or corticosteroid-resistant. Their use is not without potential adverse effects and not all patients respond well to these agents. With the introduction of biologic agents, notably the tumor necrosis factor-alpha monoclonal antibody infliximab, progress has been made in targeting specific pathogenetic mechanisms of Crohn disease and potentially altering the underlying disease process. Published experience in children is currently limited, but infliximab has been shown to improve symptoms and achieve corticosteroid independence in this age group. Unresolved issues with infliximab and other emerging biologic agents, including long-term safety, necessitate a degree of caution in selecting appropriate patients for treatment and with careful monitoring of their effects. The collection of contemporary natural history data is crucial to facilitate the better integration of current and emerging therapies in an attempt to alter the natural history of Crohn disease in children.
Collapse
Affiliation(s)
- Jeffrey S Hyams
- Division of Digestive Diseases and Nutrition, Connecticut Children's Medical Center, Hartford, CT 06106, USA.
| | | |
Collapse
|
|
37
|
Vernier G, Sendid B, Poulain D, Colombel JF. Relevance of serologic studies in inflammatory bowel disease. Curr Gastroenterol Rep 2004; 6:482-7. [PMID: 15527678 DOI: 10.1007/s11894-004-0070-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/01/2023]
Abstract
The serologic panel for inflammatory bowel disease (IBD) is rapidly expanding. Antineutrophil cytoplasmic antibodies (ANCA) and anti-Saccharomyces cerevisiae mannan antibodies (ASCA) have remained the most widely studied markers, but immune reactivity against a new group of bacterial antigens such as I2, OmpC (outer membrane porin C), and flagellin, has been described in Crohn's disease. Several clinical avenues have been explored, such as the usefulness of serologic markers as screening tools for IBD and in accelerating a diagnosis in patients with indeterminate colitis. Another area of interest is disease stratification. Emerging data suggest there is a diversity of qualitative and quantitative responses to environmental antigens that differs among groups of IBD patients and may be associated with different clinical behaviors. As a result, it may be possible to tailor therapy on the basis of serologic responses. Prospective studies are needed before translating this concept into clinical practice. Clustering of IBD patients into more homogeneous subgroups based on antibody responses may help to unravel the pathophysiology of subsets of IBD.
Collapse
Affiliation(s)
- Gwenola Vernier
- Service des Maladies de l'Appareil Digestif et de la Nutrition, CHRU Claude Huriez, Lille, France
| | | | | | | |
Collapse
|
|
38
|
Arnott IDR, Landers CJ, Nimmo EJ, Drummond HE, Smith BKR, Targan SR, Satsangi J. Sero-reactivity to microbial components in Crohn's disease is associated with disease severity and progression, but not NOD2/CARD15 genotype. Am J Gastroenterol 2004; 99:2376-84. [PMID: 15571586 DOI: 10.1111/j.1572-0241.2004.40417.x] [Citation(s) in RCA: 172] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Antibodies directed against the porin protein C of Escherichia coli (anti-OmpC) and Pseudomonas fluorescens (anti-I2) have recently been described in Crohn's disease (CD). Those directed against Saccharomyces cerevisiae (ASCA) and the perinuclear component of neutrophils (pANCA) have been more widely studied and may be of diagnostic importance. We aimed to assess the frequency of anti-OmpC, anti-I2, ASCA, and pANCA, in an independent Scottish CD cohort, establish phenotypic associations, and compare with a U.S. cohort. METHODS One hundred and forty-two well-characterized CD patients (76 females, median age 39 yr (17-88)) were studied. CD was classified by the Vienna classification. Sera were assayed for anti-OmpC, anti-I2, ASCA, and pANCA. Allele specific primers were used for NOD2/CARD15 genotyping. RESULTS Anti-OmpC, anti-I2, ASCA, and pANCA were present in sera from 37%, 52%, 39%, and 14% of CD patients, respectively. Multivariate analysis demonstrated independent associations of anti-OmpC to be progression of disease type (p= 0.005) and long disease duration (p= 0.002), and those of anti-I2 to be long disease duration (p= 0.002) and the need for surgery (p= 0.033). ASCA were associated with disease progression (p < 0.001). When the presence and magnitude of all antibody responses were considered, reactivity to microbial components was associated with long disease duration (p < 0.001), progression of disease type (p < 0.001), penetrating disease (p= 0.008), small bowel disease (p < 0.02), and the need for surgery (p < 0.001). There was no association of antibody status to NOD2/CARD15 genotype. CONCLUSION Reactivity to microbial components is associated with severe CD characterized by small bowel involvement, frequent disease progression, longer disease duration, and greater need for intestinal surgery.
Collapse
Affiliation(s)
- Ian D R Arnott
- Gastrointestinal Unit, University of Edinburgh Department of Medical Sciences, School of Clinical and Molecular Medicine, Western General Hospital, Edinburgh EH4 2XU, UK
| | | | | | | | | | | | | |
Collapse
|
|
39
|
Abstract
Ulcerative colitis (UC) is an inflammatory destructive disease of the large intestine occurred usually in the rectum and lower part of the colon as well as the entire colon. Drug therapy is not the only choice for UC treatment and medical management should be as a comprehensive whole. Azulfidine, Asacol, Pentasa, Dipentum, and Rowasa all contain 5-aminosalicylic acid (5-ASA), which is the topical anti-inflammatory ingredient. Pentasa is more commonly used in treating Crohn’s ileitis because Pentasa capsules release more 5-ASA into the small intestine than Asacol tablets. Pentasa can also be used for treating mild to moderate UC. Rowasa enemas are safe and effective in treating ulcerative proctitis and proctosigmoiditis. The sulfa-free 5-ASA agents (Asacol, Pentasa, Dipentum and Rowasa) have fewer side effects than sulfa-containing Azulfidine. In UC patients with moderate to severe disease and in patients who failed to respond to 5-ASA compounds, systemic (oral) corticosteroids should be used. Systemic corticosteroids (prednisone, prednisolone, cortisone, etc.) are potent and fast-acting drugs for treating UC, Crohn’s ileitis and ileocolitis. Systemic corticosteroids are not effective in maintaining remission in patients with UC. Serious side effects can result from prolonged corticosteroid treatment. To minimize side effects, corticosteroids should be gradually reduced as soon as the disease remission is achieved. In patients with corticosteroid-dependent or unresponsive to corticosteroid treatment, surgery or immunomodulator is considered. Immunomodulators used for treating severe UC include azathioprine/6-MP, methotrexate, and cyclosporine. Integrated traditional Chinese and Western medicine is safe and effective in maintaining remission in patients with UC.
Collapse
Affiliation(s)
- Chang-Tai Xu
- Editorial Department, Journal of Fourth Military Medical University, Fourth Military Medical University, 17 Changle West Road, Xi'an 710032, Shaanxi Province, China.
| | | | | |
Collapse
|
|
40
|
Abstract
PURPOSE OF REVIEW Inflammatory bowel disease is characterized by chronic intestinal inflammation in the absence of a recognized pathogen. In its classic description, there are two principal forms of inflammatory bowel disease: Crohn disease and ulcerative colitis. The clinical heterogeneity of these disorders alludes to the possibility of diverse pathogenetic mechanisms underlying inflammatory bowel diseases. The purpose of this review is to summarize the latest information on biomarkers of Crohn disease and ulcerative colitis. RECENT FINDINGS The authors have focused on serologic markers for which emerging data support their use as predictors of disease evolution. Serologic markers such as perinuclear antineutrophil cytoplasmic antibody, anti-Saccharomyces cerevisiae antibody, anti-OmpC, and anti-I2 may be useful in distinguishing inflammatory bowel diseases from functional disorders and ulcerative colitis from Crohn disease and predicting complications of disease. Genetic markers such as CARD15/NOD2 may be useful in the future when combined with other markers to predict disease course. Biochemical markers of inflammation such as C-reactive protein are useful to stratify patients likely to respond to biologic therapies and to follow response to treatment. In the future, functional genomics and proteomics will be used to rapidly screen patients for subclinical characteristics that can predict disease course and response to therapy. SUMMARY A variety of biomarkers can be used to stratify patients with inflammatory bowel disease into more homogeneous subgroups with respect to response to therapy and disease progression.
Collapse
Affiliation(s)
- Simon W Beaven
- Basic and Translational Research, Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA
| | | |
Collapse
|
|
41
|
Oshitani N. Anti-Saccharomyces cerevisiae antibody and 5-aminosalicylic acid treatment. Am J Gastroenterol 2004; 99:955; author reply 956. [PMID: 15128369 DOI: 10.1111/j.1572-0241.2004.40044.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
|
|
42
|
Desir B, Amre DK, Lu SE, Ohman-Strickland P, Dubinsky M, Fisher R, Seidman EG. Utility of serum antibodies in determining clinical course in pediatric Crohn's disease. Clin Gastroenterol Hepatol 2004; 2:139-46. [PMID: 15017619 DOI: 10.1016/s1542-3565(03)00321-5] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS The utility of serial measurements of anti-Saccharomyces cerevisiae (ASCA) and perinuclear antineutrophil cytoplasmic (p-ANCA) antibodies in Crohn's disease (CD) evolution is unknown. We aimed to study the pattern of antibody change and the prognosis of selected outcomes by baseline (at time of diagnosis) and serial antibody measurements in pediatric CD patients. METHODS Serum ASCA and p-ANCA antibodies were measured at baseline (n = 154) and repeated during follow-up (n = 61) using standard techniques in a cohort of patients identified at Hôpital Sainte-Justine between 1996 and 1998. Clinical information was abstracted from medical charts. Antibody patterns were examined using mixed modeling techniques. The prognostic ability of antibodies for selected outcomes was evaluated using logistic regression. RESULTS Fifteen (24.5%), 18 (29.5%), and 11 (18%) patients with serial antibody measurements changed their ASCA-IgA, ASCA-IgG, and p-ANCA status (positivity), respectively. No distinct patterns in the evolution of antibody titers were noted. Baseline ASCA-IgA positivity significantly predicted relapses during disease course (IgA: odds ratio [OR], 2.9; 95% confidence interval [CI], 1.33-6.35). Serial antibody measurements did not predict the occurrence of clinical outcomes. CONCLUSIONS Baseline serum antibodies were predictive of a more relapsing disease course in pediatric CD. However, the limited variability in the antibodies over time and the inability of serial measurements to predict clinical outcomes may limit their use in the establishment of intervention strategies.
Collapse
Affiliation(s)
- Barbara Desir
- Department of Pediatrics, Division of Gastroenterology and Nutrition, University of Montreal, Montreal, Quebec, Canada
| | | | | | | | | | | | | |
Collapse
|