HLA associations in aurothioglucose- and D-penicillamine-induced haematotoxic reactions in rheumatoid arthritis

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Abstract
HLA phenotype frequencies were studied in 21 rheumatoid arthritis (RA) patients with haematotoxic reactions to aurothioglucose (AuTG) or D-penicillamine (DP), 65 matched RA controls and 277 healthy controls. Antigens B8 and DR3 were significantly increased in the toxic RA patient group as compared to both RA controls and healthy controls. These contrasts were strongest in the patients with AuTG-induced thrombocytopenia or leucopenia: all patients developing either reaction to this drug were B8- and/or DR3-positive (p <0.001), 7 (78%) being positive for both antigens. In the patient group with DP-induced reactions these antigens were also increased but these differences were not significant. In the latter group the prevalence of antigen DR4 was high, especially in the patient group with DP-induced thrombocytopenia, all 12 patients with this type of reaction being DR4 positive. Our data suggest that haematotoxic reactions to AuTG and DP develop primarily (or even exclusively) in genetically predisposed RA patients. Furthermore, the HLA phenotype contributing to an increased risk seems not to be the same for the two anti-rheumatic drugs studied.