Wooley P H, Griffin J, Panayi G S, Batchelor J R, Welsh K I, Gibson T J
N Engl J Med. 1980 Aug 7;303(6):300-2. doi: 10.1056/NEJM198008073030602.
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.
为了研究某些HLA抗原与金硫代苹果酸钠或青霉胺治疗类风湿关节炎期间毒性反应之间的可能关系，我们对91例类风湿关节炎患者进行了研究。71例患者对其中一种药物或两种药物均有毒性反应；其余20例患者服用其中一种药物至少6个月，未出现毒性反应。在出现蛋白尿的24例患者中，19例HLA - B8和HLA - DRW3抗原呈阳性；在15例金硫代苹果酸钠诱导的蛋白尿发作中，有14例以及在13例青霉胺诱导的蛋白尿发作中，有9例发生在具有这些抗原的患者中。24小时尿蛋白超过2g的所有13例蛋白尿发作均发生在DRw3阳性的患者中。HLA - DRw3阳性的患者在金硫代苹果酸钠治疗期间出现蛋白尿的相对风险增加了32倍。未发现任何HLA抗原与皮疹或血液学并发症的发生之间存在显著关联。类风湿关节炎患者在金硫代苹果酸钠或青霉胺治疗期间的毒性反应可能受遗传控制。
