HLA-DRB1*08:02 Is Associated With Bucillamine-Induced Proteinuria In Japanese Rheumatoid Arthritis Patients: A Case-Control Study

Hiroshi Furukawa¹, Shomi Oka¹, Kota Shimada², Shoji Sugii², Atsushi Hashimoto³, Akiko Komiya¹, Naoshi Fukui¹, Taiichiro Miyashita⁴, Kiyoshi Migita⁴, Akiko Suda⁵, Shouhei Nagaoka⁶, Naoyuki Tsuchiya⁷ and Shigeto Tohma¹, ¹Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan, ²Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan, ³Department of Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan, ⁴Clinical Research Center, Nagasaki Medical Center, National Hospital Organization, Omura, Japan, ⁵Center for Rheumatic Diseases, Yokohama City University Medical Center, Yokohama, Japan, ⁶Department of Rheumatology, Yokohama Minami Kyousai Hospital, Yokohama, Japan, ⁷Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Adverse events, DMARDs, Genetic Biomarkers, human leukocyte antigens (HLA) and proteinuria

Session Information

Title: Genetics and Genomics of Rheumatic Disease I

Session Type: Abstract Submissions (ACR)

Background/Purpose: Bucillamine (Buc) is one of the commonly used disease-modifying anti-rheumatic drugs (DMARDs) in Japan. Drug-induced proteinuria can occur in rheumatoid arthritis (RA) patients treated with 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 which 25 had developed BI-Pro.

Results: This study showed a highly significant association of DRB1*08:02 with BI-Pro (P=1.09X10^-6, corrected P [Pc]=1.96X10^-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=2.44X10^-5, Pc=2.69X10^-4, OR 10.35, 95%CI 3.99-26.83).

Conclusion: We detected striking HLA class II associations with proteinuria induced by Buc in Japanese RA patients. This association merits confirmation in future large-scale studies for its potential clinical usefulness as a biomarker to prevent adverse reactions.

Disclosure:

H. Furukawa,

Research Grants from Takeda Science Foundation,

Research Grants from Mitsui Sumitomo Insurance Welfare Foundation,

S. Oka,
None;

K. Shimada,
None;

S. Sugii,
None;

A. Hashimoto,

Research grants from Mitsuibishi Tanabe Pharma Corporation,

A. Komiya,
None;

N. Fukui,
None;

T. Miyashita,
None;

K. Migita,
None;

A. Suda,
None;

S. Nagaoka,
None;

N. Tsuchiya,
None;

S. Tohma,

Research grants from Pfizer Japan Inc.,

Research grants from Astellas Pharma Inc.,

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