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. 2017 Sep 12;19(1):199.
doi: 10.1186/s13075-017-1406-x.

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

Tomoyuki Asano  1 , Hiroshi Furukawa  2 , Shuzo Sato  1 , Makiko Yashiro  1 , Hiroko Kobayashi  1 , Hiroshi Watanabe  1 , Eiji Suzuki  3 , Tomoyuki Ito  4 , Yoshifumi Ubara  5 , Daisuke Kobayashi  6 , Nozomi Iwanaga  7 , Yasumori Izumi  7 , Keita Fujikawa  8 , Satoshi Yamasaki  9 , Tadashi Nakamura  10 , Tomohiro Koga  11 , Toshimasa Shimizu  11 , Masataka Umeda  11 , Fumiaki Nonaka  12 , Michio Yasunami  13 , Yukitaka Ueki  14 , Katsumi Eguchi  14 , Naoyuki Tsuchiya  2 , Shigeto Tohma  15 , Koh-Ichiro Yoshiura  16 , Hiromasa Ohira  17 , Atsushi Kawakami  11 , Kiyoshi Migita  18
Affiliations

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

Tomoyuki Asano et al. Arthritis Res Ther. .

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.

Keywords: Adult onset Still’s disease; Autoinflammatory disease; Human leukocyte antigen; Macrophage-activation syndrome; Systemic juvenile idiopathic arthritis.

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Conflict of interest statement

Ethics approval and consent to participate

Ethical approval for this study (number 21003) was provided by the Ethics Committee of Nagasaki Medical Center and written informed consent was obtained from each individual.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Association between amino acid residues in the DRβ chain and adult onset Still’s disease. Differences in amino acid residue carrier frequencies were analyzed by Fisher’s exact test using 2 × 2 contingency tables. Corrected p (Pc) values were calculated by multiplying the p value by the number of amino acid residues tested. Predisposing association is indicated by filled circles and protective association by open circles
See this image and copyright information in PMC

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