HLA-DR Antigens and Toxic Reaction to Sodium Aurothiomalate and D-Penicillamine in Patients with Rheumatoid Arthritis

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Abstract
To investigate the possible relation between certain HLA antigens and toxicity during treatment with sodium aurothiomalate or D-penicillamine, we studied 91 patients with rheumatoid arthritis. Seventy-one had toxic reactions to either drug or both drugs; the remaining 20 took one of the drugs for at least six months, without toxicity. Nineteen of 24 patients in whom proteinuria developed were positive for HLA-B8 and HLA-DRw3 antigens; 14 of 15 episodes of aurothiomalate-induced proteinuria and nine of 13 episodes of penicillamine-induced proteinuria occurred in patients with these antigens. All 13 episodes of proteinuria in which urinary protein exceeded 2 g in 24 hours occurred in patients with DRw3. The relative risk of proteinuria during treatment with aurothiomalate is increased 32 times in patients who are HLADRw3 positive. No significant associations were found between any HLA antigen and development of skin rashes or hematologic complications.