Interaction between seroreactivity to microbial antigens and genetics in Crohn's disease: Is there a role for defensins?

Research output: Contribution to journalArticle

  • 20 Citations

Abstract

Antibodies against different microbial epitopes are associated with disease phenotype, may be of diagnostic importance and may reflect a loss of tolerance in Crohn's disease (CD). Recently, an association was reported between the presence of these antibodies and mutations in pattern receptor genes. Our aim was to investigate whether mutations in various genes other than NOD2/CARD15 or TLR4 associated with CD (NOD1/CARD4, DLG5 and DEFB1) may influence the presence of antibodies against bacterial proteins and carbohydrates in a Hungarian cohort of CD patients. Three hundred and seventy-six well-characterized, unrelated, consecutive CD patients (male/female: 191/185, age at onset: 29.1 ± 12.9 years, duration: 7.9 ± 11.7 years) were investigated. Sera were assayed for anti-Omp, anti-Saccharomyces cerevisiae antibodies (ASCAs) immunoglobulin (Ig) A and IgG, and antibodies against a mannan epitope of S. cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). NOD1/CARD4, DLG5 and DEFB1 variants were tested by polymerase chain reaction-restriction fragment length polymorphism, and DEFB1 was genotyped in a subgroup of 160 patients. Detailed clinical phenotypes were determined by reviewing the patients' medical charts. The carriage of DEFB1 20A variant alleles less frequently led to antiglycan positivity compared with patients without (29.6% vs 46.2%, OR: 0.49, 95% CI: 0.25-0.97), regardless of disease location or behavior. Similar tendency was observed for DEFB1 44G (present: 21.6% vs absent: 10.2%, P = 0.06) and ALCA. A gene or serology dosage effect was not observed. However, no association was found between the DEFB1 G52A, DLG5 R30Q, and NOD1/CARD4 E266K variants and any of the serology markers. We found that variants in human β-defensin 1 gene are inversely associated with antiglycan antibodies, further confirming an important role for innate immunity in the pathogenesis of CD.

LanguageEnglish
Pages552-559
Number of pages8
JournalTissue Antigens
Volume71
Issue number6
DOIs
Publication statusPublished - Jun 2008

Fingerprint

Microbial Genetics
Defensins
Crohn Disease
Antigens
Antibodies
Serology
Genes
Saccharomyces cerevisiae
Epitopes
Tranexamic Acid
Phenotype
Mannans
Mutation
Bacterial Proteins
Age of Onset
Innate Immunity
Restriction Fragment Length Polymorphisms
Immunoglobulin A
Immunoglobulin G
Alleles

Keywords

  • Antiglycan
  • Crohn's disease
  • DEFB1
  • DLG5
  • GASCA
  • NOD1/CARD4
  • Omp

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

@article{34f073b6374846eba00d2016e41001c8,
title = "Interaction between seroreactivity to microbial antigens and genetics in Crohn's disease: Is there a role for defensins?",
abstract = "Antibodies against different microbial epitopes are associated with disease phenotype, may be of diagnostic importance and may reflect a loss of tolerance in Crohn's disease (CD). Recently, an association was reported between the presence of these antibodies and mutations in pattern receptor genes. Our aim was to investigate whether mutations in various genes other than NOD2/CARD15 or TLR4 associated with CD (NOD1/CARD4, DLG5 and DEFB1) may influence the presence of antibodies against bacterial proteins and carbohydrates in a Hungarian cohort of CD patients. Three hundred and seventy-six well-characterized, unrelated, consecutive CD patients (male/female: 191/185, age at onset: 29.1 ± 12.9 years, duration: 7.9 ± 11.7 years) were investigated. Sera were assayed for anti-Omp, anti-Saccharomyces cerevisiae antibodies (ASCAs) immunoglobulin (Ig) A and IgG, and antibodies against a mannan epitope of S. cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). NOD1/CARD4, DLG5 and DEFB1 variants were tested by polymerase chain reaction-restriction fragment length polymorphism, and DEFB1 was genotyped in a subgroup of 160 patients. Detailed clinical phenotypes were determined by reviewing the patients' medical charts. The carriage of DEFB1 20A variant alleles less frequently led to antiglycan positivity compared with patients without (29.6{\%} vs 46.2{\%}, OR: 0.49, 95{\%} CI: 0.25-0.97), regardless of disease location or behavior. Similar tendency was observed for DEFB1 44G (present: 21.6{\%} vs absent: 10.2{\%}, P = 0.06) and ALCA. A gene or serology dosage effect was not observed. However, no association was found between the DEFB1 G52A, DLG5 R30Q, and NOD1/CARD4 E266K variants and any of the serology markers. We found that variants in human β-defensin 1 gene are inversely associated with antiglycan antibodies, further confirming an important role for innate immunity in the pathogenesis of CD.",
keywords = "Antiglycan, Crohn's disease, DEFB1, DLG5, GASCA, NOD1/CARD4, Omp",
author = "P. Lakatos and I. Altorjay and Y. M{\'a}ndi and L. Lakatos and J. Tumpek and A. Kov{\'a}cs and T. Moln{\'a}r and Z. Tulassay and P. Miheller and K. Palatka and T. Szamosi and S. Fischer and J. Papp and P. Fuszek and Orsolya Gemela and Horvath, {Henrik Csaba} and P. Vargha and F. Szalay and Z. Erd{\'e}lyi and G. Mester and Csaba Molnar and T. Pand{\'u}r and F. Nagy and J. Lonovics and Levente Balint and P. Demeter and Istvan Dobo and Ferenc Huoranszky and L. Hersz{\'e}nyi and A. N{\'e}meth and M. Papp",
year = "2008",
month = "6",
doi = "10.1111/j.1399-0039.2008.01049.x",
language = "English",
volume = "71",
pages = "552--559",
journal = "HLA",
issn = "2059-2302",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Interaction between seroreactivity to microbial antigens and genetics in Crohn's disease

T2 - HLA

AU - Lakatos, P.

AU - Altorjay, I.

AU - Mándi, Y.

AU - Lakatos, L.

AU - Tumpek, J.

AU - Kovács, A.

AU - Molnár, T.

AU - Tulassay, Z.

AU - Miheller, P.

AU - Palatka, K.

AU - Szamosi, T.

AU - Fischer, S.

AU - Papp, J.

AU - Fuszek, P.

AU - Gemela, Orsolya

AU - Horvath, Henrik Csaba

AU - Vargha, P.

AU - Szalay, F.

AU - Erdélyi, Z.

AU - Mester, G.

AU - Molnar, Csaba

AU - Pandúr, T.

AU - Nagy, F.

AU - Lonovics, J.

AU - Balint, Levente

AU - Demeter, P.

AU - Dobo, Istvan

AU - Huoranszky, Ferenc

AU - Herszényi, L.

AU - Németh, A.

AU - Papp, M.

PY - 2008/6

Y1 - 2008/6

N2 - Antibodies against different microbial epitopes are associated with disease phenotype, may be of diagnostic importance and may reflect a loss of tolerance in Crohn's disease (CD). Recently, an association was reported between the presence of these antibodies and mutations in pattern receptor genes. Our aim was to investigate whether mutations in various genes other than NOD2/CARD15 or TLR4 associated with CD (NOD1/CARD4, DLG5 and DEFB1) may influence the presence of antibodies against bacterial proteins and carbohydrates in a Hungarian cohort of CD patients. Three hundred and seventy-six well-characterized, unrelated, consecutive CD patients (male/female: 191/185, age at onset: 29.1 ± 12.9 years, duration: 7.9 ± 11.7 years) were investigated. Sera were assayed for anti-Omp, anti-Saccharomyces cerevisiae antibodies (ASCAs) immunoglobulin (Ig) A and IgG, and antibodies against a mannan epitope of S. cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). NOD1/CARD4, DLG5 and DEFB1 variants were tested by polymerase chain reaction-restriction fragment length polymorphism, and DEFB1 was genotyped in a subgroup of 160 patients. Detailed clinical phenotypes were determined by reviewing the patients' medical charts. The carriage of DEFB1 20A variant alleles less frequently led to antiglycan positivity compared with patients without (29.6% vs 46.2%, OR: 0.49, 95% CI: 0.25-0.97), regardless of disease location or behavior. Similar tendency was observed for DEFB1 44G (present: 21.6% vs absent: 10.2%, P = 0.06) and ALCA. A gene or serology dosage effect was not observed. However, no association was found between the DEFB1 G52A, DLG5 R30Q, and NOD1/CARD4 E266K variants and any of the serology markers. We found that variants in human β-defensin 1 gene are inversely associated with antiglycan antibodies, further confirming an important role for innate immunity in the pathogenesis of CD.

AB - Antibodies against different microbial epitopes are associated with disease phenotype, may be of diagnostic importance and may reflect a loss of tolerance in Crohn's disease (CD). Recently, an association was reported between the presence of these antibodies and mutations in pattern receptor genes. Our aim was to investigate whether mutations in various genes other than NOD2/CARD15 or TLR4 associated with CD (NOD1/CARD4, DLG5 and DEFB1) may influence the presence of antibodies against bacterial proteins and carbohydrates in a Hungarian cohort of CD patients. Three hundred and seventy-six well-characterized, unrelated, consecutive CD patients (male/female: 191/185, age at onset: 29.1 ± 12.9 years, duration: 7.9 ± 11.7 years) were investigated. Sera were assayed for anti-Omp, anti-Saccharomyces cerevisiae antibodies (ASCAs) immunoglobulin (Ig) A and IgG, and antibodies against a mannan epitope of S. cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). NOD1/CARD4, DLG5 and DEFB1 variants were tested by polymerase chain reaction-restriction fragment length polymorphism, and DEFB1 was genotyped in a subgroup of 160 patients. Detailed clinical phenotypes were determined by reviewing the patients' medical charts. The carriage of DEFB1 20A variant alleles less frequently led to antiglycan positivity compared with patients without (29.6% vs 46.2%, OR: 0.49, 95% CI: 0.25-0.97), regardless of disease location or behavior. Similar tendency was observed for DEFB1 44G (present: 21.6% vs absent: 10.2%, P = 0.06) and ALCA. A gene or serology dosage effect was not observed. However, no association was found between the DEFB1 G52A, DLG5 R30Q, and NOD1/CARD4 E266K variants and any of the serology markers. We found that variants in human β-defensin 1 gene are inversely associated with antiglycan antibodies, further confirming an important role for innate immunity in the pathogenesis of CD.

KW - Antiglycan

KW - Crohn's disease

KW - DEFB1

KW - DLG5

KW - GASCA

KW - NOD1/CARD4

KW - Omp

UR - http://www.scopus.com/inward/record.url?scp=43849110585&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43849110585&partnerID=8YFLogxK

U2 - 10.1111/j.1399-0039.2008.01049.x

DO - 10.1111/j.1399-0039.2008.01049.x

M3 - Article

VL - 71

SP - 552

EP - 559

JO - HLA

JF - HLA

SN - 2059-2302

IS - 6

ER -