Activation of gold-reactive T lymphocytes in rheumatoid arthritis patients treated with gold.
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.


CONCLUSIONS
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.
Verwilghen
J
J
Department of Medicine, United Medical School, Guy's Hospital, London, England.
Kingsley
G H
GH
Gambling
L
L
Panayi
G S
GS
D000328:Adult; D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced; D003300:Copper / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D003872:Dermatitis / Q000209:etiology; D005260:Female; D006046:Gold / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009532:Nickel / Q000494:pharmacology; D010984:Platinum / Q000494:pharmacology; D011507:Proteinuria / Q000139:chemically induced; D013601:T-Lymphocytes / Q000276:immunology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D014316:Tritium; D010984:Platinum; D006046:Gold; D003300:Copper; D009532:Nickel; D004247:DNA; D013936:Thymidine