Association Between HLA–DPB1 and Antineutrophil Cytoplasmic Antibody–Associated Vasculitis in Children

血管炎 医学 抗中性粒细胞胞浆抗体 免疫学 遗传倾向 等位基因 人类白细胞抗原 队列 优势比 人口 疾病 内科学 抗原 生物 遗传学 基因 环境卫生
作者
Kristen M. Gibson,Britt I. Drögemöller,Dirk Foell,Susanne M. Benseler,Jinko Graham,Robert E. W. Hancock,Raashid Luqmani,David A. Cabral,Kelly L. Brown,Colin J.D. Ross
出处
期刊:Arthritis & rheumatology [Wiley]
卷期号:75 (6): 1048-1057 被引量:3
标识
DOI:10.1002/art.42423
摘要

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare, life-threatening inflammation of blood vessels that can affect both adults and children. Compared to adult-onset disease, AAV is especially rare in children, with an annual prevalence of 0.5-6.4 cases per million children. The etiology of AAV remains largely unknown, and both environmental and genetic factors are likely involved. The present study was undertaken to explore the genetic susceptibility factors recently identified in adult patients, including HLA-DP and HLA-DQ, in pediatric patients.We performed a genome-wide association study of pediatric AAV in patients of European ancestry (n = 63 AAV cases, n = 315 population-matched controls).We identified a significant genetic association between pediatric AAV and the HLA-DPB1*04:01 allele (P = 1.5 × 10-8 , odds ratio [OR] 3.5), with a stronger association observed in children with proteinase 3-ANCA positivity than in children with myeloperoxidase-ANCA positivity. Among the HLA alleles, the HLA-DPB1*04:01 allele was the most highly associated with AAV, although not significantly, in a follow-up adult AAV cohort (P = 2.6 × 10-4 , OR 0.4). T cell receptor and interferon signaling pathways were also shown to be enriched in the pediatric AAV cohort.The HLA-DPB1 locus showed an association with pediatric AAV, as similarly shown previously in adult AAV. Despite the difference in the age of onset, these findings suggest that childhood- and adult-onset vasculitis share a common genetic predisposition. The identification of genetic variants contributing to AAV is an important step to improved classification tools and treatment strategies.
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