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

• Published in: PloS one 2016-01, Vol.11 (1), p.e0146048-e0146048
• Main Authors: Maeda, Yasuhiro, Migita, Kiyoshi, Higuchi, Osamu, Mukaino, Akihiro, Furukawa, Hiroshi, Komori, Atsumasa, Nakamura, Minoru, Hashimoto, Satoru, Nagaoka, Shinya, Abiru, Seigo, Yatsuhashi, Hiroshi, Matsuo, Hidenori, Kawakami, Atsushi, Yasunami, Michio, Nakane, Shunya
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Age of Onset; Aged; Aged, 80 and over; Alcohol; Alleles; Antibodies; Antigens; Asian Continental Ancestry Group - genetics; Autoantibodies - immunology; Autoimmune diseases; Autoimmune Diseases - epidemiology; Biology and Life Sciences; Case-Control Studies; Comorbidity; Deoxyribonucleic acid; DNA; Drb1 protein; Female; Follow-Up Studies; Gene Frequency; Genes, MHC Class I; Genes, MHC Class II; Genetic Predisposition to Disease; Genotype; Hepatitis; Hepatitis, Autoimmune - ethnology; Hepatitis, Autoimmune - genetics; Hepatitis, Autoimmune - immunology; Hepatology; Histocompatibility antigen HLA; HLA Antigens - genetics; HLA-D Antigens - genetics; HLA-DRB1 Chains - genetics; Humans; Immunoglobulins; Immunoprecipitation; Japan; Liver diseases; Male; Medicine and Health Sciences; Middle Aged; Nerve Tissue Proteins - immunology; Patients; Physical Sciences; Population genetics; Receptors, Nicotinic - immunology; Research and Analysis Methods; Rheumatoid arthritis; University graduates; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0146048

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. 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. 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. 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.