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

Hiroshi Furukawa,Akira Okamoto,Akiko Komiya,Taiichiro Miyashita,Keigo Setoguchi,Shomi Oka,Kota Shimada,Kiyoshi Migita,Naoshi Fukui,Naoyuki Tsuchiya,Eiichi Suematsu,Atsushi Hashimoto,Shigeto Tohma,Shunsei Hirohata,Tatsuo Nagai,Nobutaka Chiba ,Arnold J Suda ,Shinya Nagaoka ,Shoji Suzuki

doi:10.1371/journal.pone.0053910

Abstract

IntroductionAutoantibodies 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.MethodsAn 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.ResultsAn 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.

Highlights

Autoantibodies to ribonucleoprotein are associated with a variety of autoimmune diseases, including rheumatoid arthritis (RA)
The DPB1*05:01 allele was associated with anti-Ro/s Syndrome (SS)-A (Pc = 0.0408, OR 1.69, 95% CI 1.19–2.41) and anti-La/SS-B antibodies (Pc = 2.4861025, OR 3.31, 95%CI 2.02–5.43) in systemic lupus erythematosus (SLE) patients
human leukocyte antigen (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

Summary

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. We investigated associations of HLA class II alleles with the presence of anti-Ro/SS-A or anti-La/SS-B antibodies in RA. The presence of autoantibodies to ribonucleoprotein is associated with a variety of autoimmune diseases, including Sjogren’s Syndrome (SS), systemic lupus erythematosus (SLE), and RA. HLA-DR2 (DRB1*15 and *16) and DR3 are strongly associated with anti- Ro/SS-A or anti-La/SS-B antibodies in European primary SS populations [5,6,7,8]. We elucidate HLA class II associations with the presence of autoantibody in Japanese RA patients

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Discussion

Conclusion