title: Pancreatic autoantibodies are associated with reactivity to microbial antibodies, penetrating disease behavior, perianal disease, and extraintestinal manifestations, but not with NOD2/CARD15 or TLR4 genotype in a Hungarian IBD cohort.
abstract: BACKGROUND
  Pancreatic autoantibodies (PAB) and goblet cell autoantibodies (GAB) are specific for Crohn's disease (CD) and ulcerative colitis (UC), but the sensitivity alone is low. Conventional antibodies and carbohydrates (glycans) are associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Our aim was to determine the accuracy of PAB and GAB autoantibodies as well as to study relevant phenotype-serotype associations.
  
  
  METHODS
  A Hungarian study cohort of 1092 subjects, including 689 well-characterized, unrelated IBD patients (CD: 579, m/f ratio: 274/305, duration: 7.9 +/- 11.2 years; UC: 110, m/f ratio: 53/57, duration: 8.9 +/- 9.8 years), 139 celiac patients, 100 healthy, and 64 non-IBD gastrointestinal controls were investigated. Sera were assayed for PAB-GAB IgA/IgG, anti-Omp, anti-Saccharomyces cerevisiae antibodies (ASCA), and anti-glycans. TLR4 and NOD2/CARD15 was tested by polymerase chain reaction / restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined.
  
  
  RESULTS
  The prevalence of PAB was significantly more frequent in CD (41.1%) versus UC (22.7%), celiac (22.3%), and controls (8% and 4.6%, P < 0.01 for each), while GAB detection was poor in all groups except UC (15.4%). In CD the combination of PAB and/or anti-glycans/ASCA increased the sensitivity to 72% and 59%, respectively, for isolated colonic disease. PAB was associated to gylcans (odds ratio [OR] 1.74,P = 0.002), ASCA IgG/IgA (OR 1.75, P = 0.002), Omp (OR 1.86, P = 0.001) as well as perforating, perianal disease, arthritis, ocular, and cutaneous manifestations (P = 0.002-0.032). In contrast, PAB and GAB antibodies were not associated with NOD2/CARD15 or TLR4, response to medical therapy, or need for surgery. No associations were found in UC.
  
  
  CONCLUSIONS
  PAB autoantibodies in combination with ASCA or anti-glycan antibodies increase the sensitivity for detecting CD, especially isolated colonic CD. Antibody response to PAB was associated with complicated disease phenotype and extraintestinal manifestations in this Eastern European IBD cohort.
authors.affiliation: 1st Department of Medicine, Semmelweis University, Budapest, Hungary. kislakpet@bel1.sote.hu
authors.forename: Peter Laszlo
authors.initials: PL
authors.lastname: Lakatos
authors.forename: Istvan
authors.initials: I
authors.lastname: Altorjay
authors.forename: Tamas
authors.initials: T
authors.lastname: Szamosi
authors.forename: Karoly
authors.initials: K
authors.lastname: Palatka
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Vitalis
authors.forename: Judit
authors.initials: J
authors.lastname: Tumpek
authors.forename: Sandor
authors.initials: S
authors.lastname: Sipka
authors.forename: Miklos
authors.initials: M
authors.lastname: Udvardy
authors.forename: Tamas
authors.initials: T
authors.lastname: Dinya
authors.forename: Laszlo
authors.initials: L
authors.lastname: Lakatos
authors.forename: Agota
authors.initials: A
authors.lastname: Kovacs
authors.forename: Tamas
authors.initials: T
authors.lastname: Molnar
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.forename: Pal
authors.initials: P
authors.lastname: Miheller
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Barta
authors.forename: Winfried
authors.initials: W
authors.lastname: Stocker
authors.forename: Janos
authors.initials: J
authors.lastname: Papp
authors.forename: Gabor
authors.initials: G
authors.lastname: Veres
authors.forename: Maria
authors.initials: M
authors.lastname: Papp
mesh_terms: D000328:Adult; D000908:Antibodies, Fungal / Q000276:immunology*; D001004:Anus Diseases / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D004247:DNA / Q000235:genetics*; D003937:Diagnosis, Differential; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005838:Genotype; D006801:Humans; D006814:Hungary; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D008297:Male; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D010179:Pancreas / Q000276:immunology; D016133:Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000908:Antibodies, Fungal; D001323:Autoantibodies; D053473:Nod2 Signaling Adaptor Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D004247:DNA