TY - JOUR
T1 - Protective role of HLA-DRB1∗13:02 against microscopic polyangiitis and MPO-ANCA-positive vasculitides in a Japanese population
T2 - A case-control study
AU - Kawasaki, Aya
AU - Hasebe, Narumi
AU - Hidaka, Misaki
AU - Hirano, Fumio
AU - Sada, Kenei
AU - Kobayashi, Shigeto
AU - Yamada, Hidehiro
AU - Furukawa, Hiroshi
AU - Yamagata, Kunihiro
AU - Sumida, Takayuki
AU - Miyasaka, Nobuyuki
AU - Tohma, Shigeto
AU - Ozaki, Shoichi
AU - Matsuo, Seiichi
AU - Hashimoto, Hiroshi
AU - Makino, Hirofumi
AU - Arimura, Yoshihiro
AU - Harigai, Masayoshi
AU - Tsuchiya, Naoyuki
N1 - Funding Information:
The authors of this manuscript read the journal's policy and have the following competing interests: AK has received a research grant from SENSHIN Medical Research Foundation, supported by an endowment from Mitsubishi Tanabe Pharma Corporation, a research grant from the Takeda Science Foundation, supported by an endowment from Takeda Pharmaceutical Company, and a research grant from Japan Rheumatism Foundation. M. Harigai has received research grants from Abbvie Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co.,Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceuticals, Pfizer Japan Inc., Sanofi-Aventis KK., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Limited, and UCB Japan. NT has received a research grant from SENSHIN Medical Research Foundation, supported by an endowment from Mitsubishi Tanabe Pharma Corporation, research grants from Japan College of Rheumatology and Japan Allergy Foundation, received speaker’s honoraria from Eisai Co., Ltd., Daiichi Sankyo Co., Ltd. and Asahi Kasei Corporation, and payment for a manuscript from Torii Pharmaceutical Co., Ltd. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. The other authors declare that they have no competing interests.
Publisher Copyright:
© 2016 Kawasaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Among antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), granulomatosis with polyangiitis (GPA) and proteinase 3-ANCA-positive AAV (PR3-AAV) are prevalent in European populations, while microscopic polyangiitis (MPA) and myeloperoxidase-ANCA-positive AAV (MPO-AAV) are predominant in the Japanese. We previously demonstrated association of DRB1∗09:01-DQB1∗03:03 haplotype, a haplotype common in East Asians but rare in the European populations, with MPA/MPO-AAV, suggesting that a population difference in HLA-class II plays a role in the epidemiology of this disease. To gain further insights, we increased the sample size and performed an extended association study of DRB1 and DPB1 with AAV subsets in 468 Japanese patients with AAV classified according to the European Medicines Agency algorithm (MPA: 285, GPA: 92, eosinophilic GPA [EGPA]: 56, unclassifiable: 35) and 596 healthy controls. Among these patients, 377 were positive for MPO-ANCA and 62 for PR3-ANCA. The significance level was set at α = 3.3×10-4 by applying Bonferroni correction. The association of DRB1∗09:01 with MPO-AAV was confirmed (allele model, P = 2.1×10-4, odds ratio [OR] = 1.57). Protective association of DRB1∗13:02 was detected against MPO-AAV (allele model, P = 2.3×10-5, OR = 0.42) and MPA (dominant model, P = 2.7×10-4, OR = 0.43). A trend toward increased frequency of DPB1∗04:01, the risk allele for GPA in European populations, was observed among Japanese patients with PR3-AAV when conditioned on DRB1∗13:02 (Padjusted = 0.0021, ORadjusted = 3.48). In contrast, the frequency of DPB1∗04:01 was decreased among Japanese patients with MPO-AAV, and this effect lost significance when conditioned on DRB1∗13:02 (Padjusted = 0.16), suggesting that DRB1∗13:02 or other allele(s) in linkage disequilibrium may be responsible for the protection. The differential association of DPB1∗04:01 with PR3-AAV and MPO-AAV and difference in DPB1∗04:01 allele frequencies between populations supported the hypothesis that the HLA-class II population difference may account in part for these epidemiologic characteristics. Furthermore, taken together with our previous observations, the haplotype carrying DRB1∗13:02 was suggested to be a shared protective factor against multiple autoimmune diseases.
AB - Among antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), granulomatosis with polyangiitis (GPA) and proteinase 3-ANCA-positive AAV (PR3-AAV) are prevalent in European populations, while microscopic polyangiitis (MPA) and myeloperoxidase-ANCA-positive AAV (MPO-AAV) are predominant in the Japanese. We previously demonstrated association of DRB1∗09:01-DQB1∗03:03 haplotype, a haplotype common in East Asians but rare in the European populations, with MPA/MPO-AAV, suggesting that a population difference in HLA-class II plays a role in the epidemiology of this disease. To gain further insights, we increased the sample size and performed an extended association study of DRB1 and DPB1 with AAV subsets in 468 Japanese patients with AAV classified according to the European Medicines Agency algorithm (MPA: 285, GPA: 92, eosinophilic GPA [EGPA]: 56, unclassifiable: 35) and 596 healthy controls. Among these patients, 377 were positive for MPO-ANCA and 62 for PR3-ANCA. The significance level was set at α = 3.3×10-4 by applying Bonferroni correction. The association of DRB1∗09:01 with MPO-AAV was confirmed (allele model, P = 2.1×10-4, odds ratio [OR] = 1.57). Protective association of DRB1∗13:02 was detected against MPO-AAV (allele model, P = 2.3×10-5, OR = 0.42) and MPA (dominant model, P = 2.7×10-4, OR = 0.43). A trend toward increased frequency of DPB1∗04:01, the risk allele for GPA in European populations, was observed among Japanese patients with PR3-AAV when conditioned on DRB1∗13:02 (Padjusted = 0.0021, ORadjusted = 3.48). In contrast, the frequency of DPB1∗04:01 was decreased among Japanese patients with MPO-AAV, and this effect lost significance when conditioned on DRB1∗13:02 (Padjusted = 0.16), suggesting that DRB1∗13:02 or other allele(s) in linkage disequilibrium may be responsible for the protection. The differential association of DPB1∗04:01 with PR3-AAV and MPO-AAV and difference in DPB1∗04:01 allele frequencies between populations supported the hypothesis that the HLA-class II population difference may account in part for these epidemiologic characteristics. Furthermore, taken together with our previous observations, the haplotype carrying DRB1∗13:02 was suggested to be a shared protective factor against multiple autoimmune diseases.
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U2 - 10.1371/journal.pone.0154393
DO - 10.1371/journal.pone.0154393
M3 - Article
C2 - 27166610
AN - SCOPUS:84969791284
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 5
M1 - e0154393
ER -