Is Associated with Bucillamine-Induced Proteinuria in Japanese Rheumatoid Arthritis Patients

Abstract

Background Drug-induced proteinuria can occur in rheumatoid arthritis (RA) patients treated with d-penicillamine, gold salts, or bucillamine (Buc), and represents a drug hypersensitivity reaction. Striking associations of human leukocyte antigen (HLA) alleles with adverse reactions have recently been reported for many drugs. Methods We investigated the association of HLA class II with Buc-induced proteinuria (BI-Pro) in 485 Japanese RA patients treated with Buc, of whom 25 had developed BI-Pro. Results and Conclusion This preliminary study showed a highly significant association of DRB1*08:02 with BI-Pro ( P = 1.09 × 10 −6 , corrected P [ Pc ] = 1.96 × 10 −5 , odds ratio [OR] 25.17, 95% confidence interval [CI] 7.98-79.38). DQB1*04:02 was also significantly associated with increased risk of BI-Pro ( P = 2.44 × 10 −5 , Pc = 2.69 × 10 −4 , OR 10.35, 95%CI 3.99–26.83). These findings provide useful information for promoting personalized medicine for RA.