Association of increased frequencies of HLA-DPB1*05:01 with the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in Japanese rheumatoid arthritis and systemic lupus erythematosus patients

PLoS One. 2013;8(1):e53910. doi: 10.1371/journal.pone.0053910. Epub 2013 Jan 8.

Abstract

Introduction: Autoantibodies to ribonucleoprotein are associated with a variety of autoimmune diseases, including rheumatoid arthritis (RA). Many studies on associations between human leukocyte antigen (HLA) alleles and RA have been reported, but few have been validated in RA subpopulations with anti-La/SS-B or anti-Ro/SS-A antibodies. Here, we investigated associations of HLA class II alleles with the presence of anti-Ro/SS-A or anti-La/SS-B antibodies in RA.

Methods: An association study was conducted for HLA-DRB1, DQB1, and DPB1 in Japanese RA and systemic lupus erythematosus (SLE) patients that were positive or negative for anti-Ro/SS-A and/or anti-La/SS-B antibodies.

Results: An increased prevalence of certain class II alleles was associated with the presence of anti-Ro/SS-A antibodies as follows: DRB1*08:03 (Pc = 3.79×10(-5), odds ratio [OR] 3.06, 95% confidence interval [CI] 1.98-4.73), DQB1*06:01 (Pc = 0.0106, OR 1.70, 95%CI 1.26-2.31), and DPB1*05:01 (Pc = 0.0040, OR 1.55, 95%CI 1.23-1.96). On the other hand, DRB1*15:01 (Pc = 0.0470, OR 3.14, 95%CI 1.63-6.05), DQB1*06:02 (Pc = 0.0252, OR 3.14, 95%CI 1.63-6.05), and DPB1*05:01 (Pc = 0.0069, OR 2.27, 95% CI 1.44-3.57) were associated with anti-La/SS-B antibodies. The DPB1*05:01 allele was associated with anti-Ro/SS-A (Pc = 0.0408, OR 1.69, 95% CI 1.19-2.41) and anti-La/SS-B antibodies (Pc = 2.48×10(-5), OR 3.31, 95%CI 2.02-5.43) in SLE patients.

Conclusion: HLA-DPB1*05:01 was the only allele associated with the presence of both anti-Ro/SS-A and anti-La/SS-B antibodies in Japanese RA and SLE patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Antinuclear / blood*
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology*
  • Asian Continental Ancestry Group / genetics
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genes, MHC Class II
  • Genetic Association Studies
  • HLA-DP beta-Chains / genetics*
  • HLA-DQ beta-Chains / genetics
  • HLA-DRB1 Chains / genetics
  • Humans
  • Japan
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Middle Aged
  • Sjogren's Syndrome / genetics
  • Sjogren's Syndrome / immunology

Substances

  • Antibodies, Antinuclear
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen
  • HLA-DPB1*05:01 antigen
  • HLA-DQ beta-Chains
  • HLA-DQbeta antigen
  • HLA-DRB1 Chains
  • SS-A antibodies
  • SS-B antibodies

Grant support

This work was supported by Grants-in-Aid for Scientific Research (B, C) (22390199, 22591090) and for Young Scientists (24791018) from the Japan Society for the Promotion of Science, Health and Labour Science Research, Grants from the Ministry of Health, Labour, and Welfare of Japan, Grants-in-Aid for Clinical Research from National Hospital Organization, Research Grants from Daiwa Securities Health Foundation, Research Grants from Japan Research Foundation for Clinical Pharmacology, Research Grants from The Nakatomi Foundation, Research Grants from the Takeda Science Foundation, and research grants from pharmaceutical companies: Abbott Japan Co., Ltd., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Merck Sharp and Dohme Inc., Pfizer Japan Inc., Takeda Pharmaceutical Company Limited and Teijin Pharma Limited. The funders had no role in study design, data collection and analysis, decision to publish, or preparing the manuscript.