Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population

PLoS One. 2016 Jan 25;11(1):e0146048. doi: 10.1371/journal.pone.0146048. eCollection 2016.

Abstract

Background/aims: Anti-ganglionic nicotinic acetylcholine receptor (gAChR) antibodies are observed in autoimmune diseases, as well as in patients with autoimmune autonomic ganglionopathy. However, the genetic background of anti-gAChR antibodies is unclear. Here, we investigated HLA alleles in autoimmune hepatitis (AIH) patients with or without anti-gAChR antibodies.

Methodology/principal findings: Genomic DNA from 260 patients with type-1 autoimmune hepatitis (AIH) were genotyped for HLA-A, B, DRB1, and DQB1 loci. Anti-gAChR antibodies in the sera form AIH patients were measured using the luciferase immunoprecipitation system, and examined allelic association in patients with or without anti-gAChR antibodies.

Methodology/ methods: We detected anti-α3 or -β4 gAChR antibodies in 11.5% (30/260) of patients with AIH. Among AIH patients there was no significant association between HLA-A, B DQB1 alleles and the positivity for anti-gAChR antibodies. Whereas the HLA-DRB1*0403 allele showed a significantly increased frequency in AIH patients with anti-gAChR antibodies compared with those without anti-gAChR antibodies.

Conclusions/significance: The frequency of the HLA-DRB1*0403 allele differed among Japanese patients with AIH according to the presence or absence of anti-gAChR antibodies. Our findings suggest that particular HLA class II molecules might control the development of anti-gAChR antibodies in the autoimmune response to gAChR.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alleles
  • Asian People / genetics*
  • Autoantibodies / immunology*
  • Autoimmune Diseases / epidemiology
  • Case-Control Studies
  • Comorbidity
  • Female
  • Follow-Up Studies
  • Gene Frequency
  • Genes, MHC Class I
  • Genes, MHC Class II
  • Genetic Predisposition to Disease
  • Genotype
  • HLA Antigens / genetics
  • HLA-D Antigens / genetics
  • HLA-DRB1 Chains / genetics*
  • Hepatitis, Autoimmune / ethnology
  • Hepatitis, Autoimmune / genetics*
  • Hepatitis, Autoimmune / immunology
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / immunology*
  • Receptors, Nicotinic / immunology*
  • Young Adult

Substances

  • Autoantibodies
  • CHRNB4 protein, human
  • HLA Antigens
  • HLA-D Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*04:03 antigen
  • Nerve Tissue Proteins
  • Receptors, Nicotinic
  • nicotinic receptor subunit alpha3

Grants and funding

This work was supported by a grant from the National Hospital Organization.