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.
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.
Lakatos
Peter Laszlo
PL
1st Department of Medicine, Semmelweis University, Budapest, Hungary. kislakpet@bel1.sote.hu
Altorjay
Istvan
I
Szamosi
Tamas
T
Palatka
Karoly
K
Vitalis
Zsuzsanna
Z
Tumpek
Judit
J
Sipka
Sandor
S
Udvardy
Miklos
M
Dinya
Tamas
T
Lakatos
Laszlo
L
Kovacs
Agota
A
Molnar
Tamas
T
Tulassay
Zsolt
Z
Miheller
Pal
P
Barta
Zsolt
Z
Stocker
Winfried
W
Papp
Janos
J
Veres
Gabor
G
Papp
Maria
M
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
D000908:Antibodies, Fungal; D001323:Autoantibodies; D053473:Nod2 Signaling Adaptor Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D004247:DNA