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

P. Lakatos, Istvan Aitorjay, T. Szamosi, K. Palatka, Zsuzsanna Vitalis, Judit Tumpek, S. Sipka, M. Udvardy, Tamas Dinya, A. Kovács, Agota Kovacs, Z. Tulassay, P. Miheller, Z. Barta, Zsolt Barta, J. Papp, G. Verès, M. Papp, Maria Papp

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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.

Original languageEnglish
Pages (from-to)365-374
Number of pages10
JournalInflammatory Bowel Diseases
Volume15
Issue number3
DOIs
Publication statusPublished - 2009

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Inflammatory Bowel Diseases
Autoantibodies
Genotype
Antibodies
Goblet Cells
Crohn Disease
Ulcerative Colitis
Polysaccharides
Saccharomyces cerevisiae
Colonic Diseases
Phenotype
Odds Ratio
Abdomen
Anti-Idiotypic Antibodies
Eye Manifestations
Skin Manifestations
Gastrointestinal Diseases
Restriction Fragment Length Polymorphisms
Immunoglobulin A
Arthritis

Keywords

  • Anti-glycan
  • ASCA
  • Diseases phenotype
  • GAB
  • IBD
  • NOD2/CARD15
  • Omp
  • PAB

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

@article{48cca424e2f543059e64b4af732daa40,
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.",
keywords = "Anti-glycan, ASCA, Diseases phenotype, GAB, IBD, NOD2/CARD15, Omp, PAB",
author = "P. Lakatos and Istvan Aitorjay and T. Szamosi and K. Palatka and Zsuzsanna Vitalis and Judit Tumpek and S. Sipka and M. Udvardy and Tamas Dinya and A. Kov{\'a}cs and Agota Kovacs and Z. Tulassay and P. Miheller and Z. Barta and Zsolt Barta and J. Papp and G. Ver{\`e}s and M. Papp and Maria Papp",
year = "2009",
doi = "10.1002/ibd.20778",
language = "English",
volume = "15",
pages = "365--374",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - 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

AU - Lakatos, P.

AU - Aitorjay, Istvan

AU - Szamosi, T.

AU - Palatka, K.

AU - Vitalis, Zsuzsanna

AU - Tumpek, Judit

AU - Sipka, S.

AU - Udvardy, M.

AU - Dinya, Tamas

AU - Kovács, A.

AU - Kovacs, Agota

AU - Tulassay, Z.

AU - Miheller, P.

AU - Barta, Z.

AU - Barta, Zsolt

AU - Papp, J.

AU - Verès, G.

AU - Papp, M.

AU - Papp, Maria

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Anti-glycan

KW - ASCA

KW - Diseases phenotype

KW - GAB

KW - IBD

KW - NOD2/CARD15

KW - Omp

KW - PAB

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U2 - 10.1002/ibd.20778

DO - 10.1002/ibd.20778

M3 - Article

VL - 15

SP - 365

EP - 374

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 3

ER -