title: Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn's disease.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Nora
authors.initials: N
authors.lastname: Sipeki
authors.affiliation: 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.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Davida
authors.affiliation: 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.
authors.forename: Eszter
authors.initials: E
authors.lastname: Palyu
authors.affiliation: 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.
authors.forename: Istvan
authors.initials: I
authors.lastname: Altorjay
authors.affiliation: 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.
authors.forename: Jolan
authors.initials: J
authors.lastname: Harsfalvi
authors.affiliation: 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.
authors.forename: Peter Antal
authors.initials: PA
authors.lastname: Szalmas
authors.affiliation: 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.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Szabo
authors.affiliation: 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.
authors.forename: Gabor
authors.initials: G
authors.lastname: Veres
authors.affiliation: 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.
authors.forename: Zakera
authors.initials: Z
authors.lastname: Shums
authors.affiliation: 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.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Norman
authors.affiliation: 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.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Lakatos
authors.affiliation: 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.
authors.forename: Maria
authors.initials: M
authors.lastname: Papp
mesh_terms: D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003093:Colitis, Ulcerative / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology; D003424:Crohn Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000628:therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D012698:Serologic Tests; D062606:Tertiary Care Centers; D055815:Young Adult
chemical_list: D017152:Antibodies, Antiphospholipid; D015415:Biomarkers
keywords: Anti-cardiolipin antibodies; Anti-phosphatidylserine/prothrombin; Anti-β2-Glycoprotein-I antibodies; Antiphospholipid antibodies; Crohn’s disease; Disease progression; Thrombosis; Ulcerative colitis