Arthritis Research and Therapy
Arthritis Research and Therapy
5 years ago

Effects of HLA-DRB1 alleles on susceptibility and clinical manifestations in Japanese patients with adult onset Still’s disease

Atsushi Kawakami, Eiji Suzuki, Fumiaki Nonaka, Tomohiro Koga, Masataka Umeda, Hiroshi Furukawa, Koh-ichiro Yoshiura, Naoyuki Tsuchiya, Kiyoshi Migita, Shuzo Sato, Katsumi Eguchi, Hiroko Kobayashi, Daisuke Kobayashi, Hiromasa Ohira, Shigeto Tohma, Keita Fujikawa, Satoshi Yamasaki, Yukitaka Ueki, Tomoyuki Asano, Yasumori Izumi, Tadashi Nakamura, Yoshifumi Ubara, Toshimasa Shimizu, Makiko Yashiro, Nozomi Iwanaga, Tomoyuki Ito, Hiroshi Watanabe, Michio Yasunami

Abstract

Background

HLA-DRB1 alleles are major determinants of genetic predisposition to rheumatic diseases. We assessed whether DRB1 alleles are associated with susceptibility to particular clinical features of adult onset Still’s disease (AOSD) in a Japanese population by determining the DRB1 allele distributions.

Methods

DRB1 genotyping of 96 patients with AOSD and 1,026 healthy controls was performed. Genomic DNA samples from the AOSD patients were also genotyped for MEFV exons 1, 2, 3, and 10 by direct sequencing.

Results

In Japanese patients with AOSD, we observed a predisposing association of DRB1*15:01 (p = 8.60 × 10−6, corrected p (Pc) = 0.0002, odds ratio (OR) = 3.04, 95% confidence interval (95% CI) = 1.91–4.84) and DR5 serological group (p = 0.0006, OR = 2.39, 95% CI = 1.49–3.83) and a protective association of DRB1*09:01 (p = 0.0004, Pc = 0.0110, OR = 0.34, 95% CI = 0.18–0.66) with AOSD, and amino acid residues 86 and 98 of the DRβ chain were protectively associated with AOSD. MEFV variants were identified in 49 patients with AOSD (56.3%). The predisposing effect of DR5 was confirmed only in patients with AOSD who had MEFV variants and not in those without MEFV variants. Additionally, DR5 in patients with AOSD are associated with macrophage activation syndrome (MAS) and steroid pulse therapy.

Conclusion

The DRB1*15:01 and DR5 are both associated with AOSD susceptibility in Japanese subjects. A protective association between the DRB1*09:01 allele and AOSD was also observed in these patients. Our data also highlight the effects of DRB1 alleles in susceptibility to AOSD.

Publisher URL: https://link.springer.com/article/10.1186/s13075-017-1406-x

DOI: 10.1186/s13075-017-1406-x

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