<i>HLA-DRB1</i> allele frequencies in Japanese patients with MPO-AAV or PR3-AAV or in healthy controls.

<p><i>HLA-DRB1</i> allele frequencies in Japanese patients with MPO-AAV or PR3-AAV or in healthy controls.</p

<i>HLA-DRB1</i> allele frequencies in Japanese patients with MPA, EGPA, or GPA or in healthy controls.

<p><i>HLA-DRB1</i> allele frequencies in Japanese patients with MPA, EGPA, or GPA or in healthy controls.</p

Protective Role of <i>HLA-DRB1*13</i>:<i>02</i> against Microscopic Polyangiitis and MPO-ANCA-Positive Vasculitides in a Japanese Population: A Case-Control Study

<div><p>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 <i>DRB1*09</i>:<i>01-DQB1*03</i>:<i>03</i> haplotype, a haplotype common in East Asians but rare in the European populations, with MPA/MPO-AAV, suggesting that a population difference in <i>HLA-class II</i> 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 <i>DRB1</i> and <i>DPB1</i> 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 = 3.3x10^-4 by applying Bonferroni correction. The association of <i>DRB1*09</i>:<i>01</i> with MPO-AAV was confirmed (allele model, P = 2.1x10^-4, odds ratio [OR] = 1.57). Protective association of <i>DRB1*13</i>:<i>02</i> was detected against MPO-AAV (allele model, P = 2.3x10^-5, OR = 0.42) and MPA (dominant model, P = 2.7x10^-4, OR = 0.43). A trend toward increased frequency of <i>DPB1*04</i>:<i>01</i>, the risk allele for GPA in European populations, was observed among Japanese patients with PR3-AAV when conditioned on <i>DRB1*13</i>:<i>02</i> (P_adjusted = 0.0021, OR_adjusted = 3.48). In contrast, the frequency of <i>DPB1*04</i>:<i>01</i> was decreased among Japanese patients with MPO-AAV, and this effect lost significance when conditioned on <i>DRB1*13</i>:<i>02</i> (P_adjusted = 0.16), suggesting that <i>DRB1*13</i>:<i>02</i> or other allele(s) in linkage disequilibrium may be responsible for the protection. The differential association of <i>DPB1*04</i>:<i>01</i> with PR3-AAV and MPO-AAV and difference in <i>DPB1*04</i>:<i>01</i> allele frequencies between populations supported the hypothesis that the <i>HLA-class II</i> population difference may account in part for these epidemiologic characteristics. Furthermore, taken together with our previous observations, the haplotype carrying <i>DRB1*13</i>:<i>02</i> was suggested to be a shared protective factor against multiple autoimmune diseases.</p></div

<i>HLA-DPB1</i> allele frequencies in Japanese patients with MPA, EGPA, or GPA or in healthy controls.

<p><i>HLA-DPB1</i> allele frequencies in Japanese patients with MPA, EGPA, or GPA or in healthy controls.</p

<i>HLA-DPB1</i> allele frequencies in Japanese patients with MPO-AAV or PR3-AAV or in healthy controls.

<p><i>HLA-DPB1</i> allele frequencies in Japanese patients with MPO-AAV or PR3-AAV or in healthy controls.</p

Conditional logistic regression analysis between <i>DRB1*13</i>:<i>02</i> and <i>DPB1*04</i>:<i>01</i> in AAV subsets.

<p>Conditional logistic regression analysis between <i>DRB1*13</i>:<i>02</i> and <i>DPB1*04</i>:<i>01</i> in AAV subsets.</p