OBJECTIVE: To assess the role of T lymphocyte sensitization in the etiology of side effects of gold therapy in patients with rheumatoid arthritis (RA). METHODS: Lymphocyte proliferation induced by gold(III) and gold(I) salts was measured in 53 subjects: 30 RA patients with gold-induced side effects (17 with dermatitis, 9 with proteinuria, 3 with hematologic complications, and 1 with colitis), 9 RA patients without side effects despite prolonged chrysotherapy, 4 RA patients who had never received gold, and 10 healthy controls. Peripheral blood lymphocytes were cultured with the different gold salts and proliferation was measured by 3H-thymidine incorporation. RESULTS: Thirteen of the 17 RA patients who developed gold-induced dermatitis showed significant T lymphocyte proliferation in response to gold(III) salts, and this proliferation could be completely blocked by monoclonal antibodies directed at the HLA-DR molecule. Such proliferative responses were not seen in patients with other gold-induced side effects, in patients who had never received gold, or in healthy controls. Only 1 of 9 patients who had not developed side effects despite long-term maintenance chrysotherapy showed significant lymphocyte activation with gold(III) salts. Lymphocyte proliferation could not be induced with gold(I) salts or with other metal salts. CONCLUSION: Patients with RA who develop dermatitis following treatment with sodium aurothiomalate [gold(I)] have T cells which proliferate in an HLA-DR-restricted manner in response to HAuCl4 [gold(III)]. We believe this observation can lead to more accurate diagnosis and treatment of side effects, which currently limit the use of one of the most effective antirheumatic drugs.
OBJECTIVE: To assess the role of T lymphocyte sensitization in the etiology of side effects of gold therapy in patients with rheumatoid arthritis (RA). METHODS: Lymphocyte proliferation induced by gold(III) and gold(I) salts was measured in 53 subjects: 30 RApatients with gold-induced side effects (17 with dermatitis, 9 with proteinuria, 3 with hematologic complications, and 1 with colitis), 9 RApatients without side effects despite prolonged chrysotherapy, 4 RApatients who had never received gold, and 10 healthy controls. Peripheral blood lymphocytes were cultured with the different gold salts and proliferation was measured by 3H-thymidine incorporation. RESULTS: Thirteen of the 17 RApatients who developed gold-induced dermatitis showed significant T lymphocyte proliferation in response to gold(III) salts, and this proliferation could be completely blocked by monoclonal antibodies directed at the HLA-DR molecule. Such proliferative responses were not seen in patients with other gold-induced side effects, in patients who had never received gold, or in healthy controls. Only 1 of 9 patients who had not developed side effects despite long-term maintenance chrysotherapy showed significant lymphocyte activation with gold(III) salts. Lymphocyte proliferation could not be induced with gold(I) salts or with other metal salts. CONCLUSION:Patients with RA who develop dermatitis following treatment with sodium aurothiomalate [gold(I)] have T cells which proliferate in an HLA-DR-restricted manner in response to HAuCl4 [gold(III)]. We believe this observation can lead to more accurate diagnosis and treatment of side effects, which currently limit the use of one of the most effective antirheumatic drugs.
Authors: Michael D Laiosa; Kevin G Eckles; Margaret Langdon; Allen J Rosenspire; Michael J McCabe Journal: Toxicol Appl Pharmacol Date: 2007-06-19 Impact factor: 4.219