Clinical Trials Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2015; 21(22): 6952-6964
Published online Jun 14, 2015. doi: 10.3748/wjg.v21.i22.6952
Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn’s disease
Nora Sipeki, Laszlo Davida, Eszter Palyu, Istvan Altorjay, Jolan Harsfalvi, Peter Antal Szalmas, Zoltan Szabo, Gabor Veres, Zakera Shums, Gary L Norman, Peter L Lakatos, Maria Papp
Nora Sipeki, Laszlo Davida, Eszter Palyu, Istvan Altorjay, Maria Papp, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Jolan Harsfalvi, Clinical Research Center, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Peter Antal Szalmas, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Zoltan Szabo, Division of Emergency Medicine, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Gabor Veres, Peter L Lakatos, 1st Department of Medicine, Semmelweis University, H-1083 Budapest, Hungary
Zakera Shums, Gary L Norman, Inova Diagnostics, Inc., San Diego, California, CA 92131, United States
Author contributions: Papp M, Lakatos PL, Antal Szalmas P, Szabo Z and Veres G designed research; Sipeki N, Papp M, Davida L, Palyu E and Altorjay I performed research; Harsfalvi J, Antal Szalmas P, Shums Z and Norman GL contributed new reagents/analytic tools; Papp M, Sipeki N and Lakatos PL analyzed data; Papp M, Sipeki N and Lakatos PL wrote paper.
Supported by Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences, Internal Research Grant of University of Debrecen and the IOIBD Research Grant.
Ethics approval: The study was reviewed and approved by the Hungarian National Review Board and the Institutional Review Board of the University of Debrecen.
Clinical trial registration: This registration policy applies to prospective, randomized, controlled trials only.
Informed consent: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest: Not declared.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Maria Papp, MD, PhD, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032 Debrecen, Hungary. papp.maria@med.unideb.hu
Telephone: +36-52-255152 Fax: +36-52-255152
Received: December 31, 2014
Peer-review started: January 4, 2015
First decision: February 10, 2015
Revised: March 1, 2015
Accepted: April 9, 2015
Article in press: April 9, 2015
Published online: June 14, 2015
Processing time: 168 Days and 20.9 Hours
Abstract

AIM: To assess the prevalence and stability of different antiphospholipid antibodies (APLAs) and their association with disease phenotype and progression in inflammatory bowel diseases (IBD) patients.

METHODS: About 458 consecutive patients [Crohn’s disease (CD): 271 and ulcerative colitis (UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients’ medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course (development f complicated disease phenotype and need for surgery), occurrence of thrombotic events, actual state of disease activity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up, (median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls (HC) were tested on individual anti-β2-Glycoprotein-I (anti-β2-GPI IgA/M/G), anti-cardiolipin (ACA IgA/M/G) and anti-phosphatidylserine/prothrombin (anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies (ASCA IgA/G) by enzyme-linked immunosorbent assay (ELISA). In a subgroup of CD (n = 198) and UC patients (n = 103), obtaining consecutive samples over various arbitrary time-points during the disease course, we evaluated the intraindividual stability of the APLA status. Additionally, we provide an overview of studies, performed so far, in which significance of APLAs in IBD were assessed.

RESULTS: Patients with CD had significantly higher prevalence of both ACA (23.4%) and anti-PS/PT (20.4%) antibodies than UC (4.8%, P < 0.0001 and 10.2%, P = 0.004) and HC (2.9%, P < 0.0001 and 15.5%, P = NS). No difference was found for the prevalence of anti-β2-GPI between different groups (7.2%-9.7%). In CD, no association was found between APLA and ASCA status of the patients. Occurrence of anti-β2-GPI, ACA and anti-PS/PT was not different between the group of patients with active vs inactive disease state according to appropriate clinical, laboratory and endoscopic scores in CD as well as in UC patients. All subtypes of anti-β2-GPI and ACA IgM status were found to be very stable over time, in contrast ACA IgG and even more ACA IgA status showed significant intraindividual changes. Changes in antibody status were more remarkable in CD than UC (ACA IgA: 49.9% vs 23.3% and ACA IgG: 21.2% vs 5.8%). Interestingly, 59.1% and 30.1% of CD patients who received anti-TNF therapy showed significant negative to positive changes in ACA IgA and IgG antibody status respectively. APLA status was not associated with the clinical phenotype at diagnosis or during follow-up, medical therapy, or thrombotic events and it was not associated with the probability of developing complicated disease phenotype or surgery in a Kaplan-Meier analysis.

CONCLUSION: The present study demonstrated enhanced formation of APLAs in CD patients. However, presence of different APLAs were not associated with the clinical phenotype or disease course.

Keywords: Crohn’s disease; Ulcerative colitis; Disease progression; Antiphospholipid antibodies; Anti-β2-Glycoprotein-I antibodies; Anti-phosphatidylserine/prothrombin; Anti-cardiolipin antibodies; Thrombosis

Core tip: Enhanced serological antibody formation is a well-known feature of inflammatory bowel diseases. Antiphospholipid antibodies (APLAs) are a prothrombotic group of antibodies acquired in various inflammatory diseases. However their association with clinical phenotype and disease progression is still unclear in inflammatory bowel diseases (IBD). In the present study we report enhanced formation of APLAs in patients with Crohn’s disease, which was not associated with clinical phenotype or disease course during follow-up in a tertiary referral IBD center from Hungary.