Genetic Association Study on HLA with Interstitial Lung Diseases in Rheumatoid Arthritis Patients.

间质性肺疾病是与类风湿关节炎（RA）相关的重要并发症。甲氨蝶呤诱导的间质性肺疾病（MI-ILD）可发生在类风湿性关节炎患者中，并代表一种潜在的危及生命的药物超敏反应。据认为，日本RA患者比其他民族更容易发生MI-ILD。人类白细胞抗原（HLA） I类等位基因与许多药物严重的皮肤不良反应有显著的关联。在这里，我们研究了HLA与RA中ILD的关系。HLA-DRB1*04、共享表位（SE）和DQB1*04与ILD风险显著降低相关。相反，DRB1*16、DR2血清学组和DQB1*06与ILD风险显著相关。我们发现a *31:01等位基因与MI-ILD高度显著相关。

Interstitial lung disease is a critical complication associated with rheumatoid arthritis (RA). Methotrexate-induced interstitial lung disease (MI-ILD) can occur in RA patients and represents a potentially life-threatening drug hypersensitivity reaction. It is believed that Japanese RA patients are more susceptible to MI-ILD than other ethnic groups. Striking association of human leukocyte antigen (HLA) class I alleles with severe cutaneous adverse reactions has recently been reported for many drugs. Here, we investigated the association of HLA with ILD in RA. HLA-DRB1*04, shared epitope (SE) and DQB1*04 were associated with significantly decreased risk of ILD. In contrast, DRB1*16, DR2 serological group and DQB1*06 were significantly associated with risk of ILD. We found a highly significant association of the A*31:01 allele with MI-ILD.