Gold thiomalate (40 pM), penicillamine (40 pM), and histidine (20 pM) inhibit the copper-catalyzed (20 pM) thermal aggregation of human gamma globulin (0.8 mg/ml). At these concentrations, inhibition of gamma globulin aggregation was 87%, 96%, and 99% complete. This effect may be related to the reported suppressive effect of these agents in rheumatoid arthritis and adds support to the hypothesis that the hypohistidinemia of rheumatoid arthritis participates in the pathogenesis of the disease.
Gold thiomalate (l), D-penicillamine (2),and L-histidine (3,4) have been reported to be effective in the treatment of rheumatoid arthritis. There is good evidence that aggregated gamma globulin is inflammatory, antigenic, and a stimulus to the formation of rheumatoid factors (5). There is also some evidence for the presence of aggregated gamma globulin in the synovial fluid of patients with rheumatoid arthritis (6,7).