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

Abstract

To investigate the possible relation between certain HLA antigens and toxicity during treatment with sodium aurothiomalate of 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 proteinura and nine of 13 episodes of penicillamine-induced proteinura 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 HLA-DRw3 positive. No significant associations were found between any HLA antigen and development of skin rashes or hematologic complications. Toxicity during aurothiomalate or penicillamine treatment for rheumatoid arthritis may be under genetic control.

Sjögren's Syndrome

“…In our primary SS patients toxicity or hypersensitivity to goldsalts were seen in 75% of cases ever treated with goldsalts and in three of three patients treated with penicillamine. These figures are in accordance with those reported by Wooley et al (68) who found side effects in 81% of rheumatoid arthritis cases treated with goldsalt -but it is important to note that the reaction to goldsalt occurred among patients who had HLA-Dw2 and/or -Dw3 (68): the antigens seen in primary SS patients. Further data are needed to verify whether side effects to goldsalts and/or penicillamine are seen especially among SS patients and perhaps primarily in those with HLADw2 and/or HLA-Dw3.…”

Dr Antigens and Gold Toxicity in white rheumatoid arthritis patients

“…This study confirms previous reports that white RA patients possessing the DR3 phenotype are at increased risk for developing toxic side effects to gold therapy (6)(7)(8)(9)(10)(11)(12)(13). This is true with respect to all adverse reactions to gold treatment since 8 of 17 patients, or 47.1% of the gold-treated patients with DR3.…”

Association between HLA-DRB1*15 and Japanese Patients with Rheumatoid Arthritis Complicated by Renal Involvement

“…DNA typing of HLA-DR alleles from patients with RA confirmed the shared epitope hypothesis, because HLA-DRB1*0401, 0404, 0405, 0408, HLA-DRB1*0101 and DRB1*1402 share the same sequence at positions 70–74 in the third exon, but DRB1*0402 and others do not [7, 14]. HLA antigens have also been reported to be associated with the reactive side effects of drugs to RA [15, 16, 17, 18, 19, 20, 21]and also with the severity of the disease [22, 23, 24, 25, 26, 27, 28, 29, 30]as well as with the susceptibility to RA with extra-articular manifestations [25, 31, 32, 33, 34, 35]. …”

“…However, a considerable number of patients with RA develop such kidney diseases as renal amyloidosis and/or toxic or allergic reactions to prescribed drugs [36, 37, 38, 39, 40]. A significant association of the presence of serological HLA-DR3 with the development of proteinuria during the treatment with aurothiomalate and D -penicillamine has been reported in Caucasian patients with RA [16, 17]. We herein report the findings of analyses of the immunogenetic backgrounds of Japanese patients with RA and RI.…”