McCune W J, Golbus J, Zeldes W, Bohlke P, Dunne R, Fox D A
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor.
N Engl J Med. 1988 Jun 2;318(22):1423-31. doi: 10.1056/NEJM198806023182203.
Severe systemic lupus erythematosus affecting the kidney or central nervous system may lead to organ failure or death despite treatment with high doses of corticosteroids. To evaluate the clinical and immunologic effects of intravenous cyclophosphamide in this setting, we treated nine patients with monthly intravenous infusions of cyclophosphamide for six months. A comparison of characteristics at entry and follow-up revealed improvements (by paired t-test) in creatinine clearance (66 vs. 96 ml per minute, P less than 0.001); 24-hour urinary protein level (4.11 vs. 0.90 g, P less than 0.05), Farr anti-DNA titer (43 vs. 8.5 percent, P less than 0.01); complement components C3 (894 vs. 1150 mg per liter, P less than 0.05), C4 (154 vs. 222 mg per liter, P less than 0.05), and total complement activity (CH50) (88.7 vs. 113.4 IU, P less than 0.05); and Westergren erythrocyte sedimentation rate (60.2 vs. 34.4 mm per hour, P less than 0.0005). Other manifestations of lupus improved markedly in most cases, despite a reduction in the mean daily dose of prednisone, from 45 mg at entry to 17 mg at follow-up (P less than 0.01). The numbers of lymphocytes positive for T3, T4, T8, and B1 declined progressively during treatment. At follow-up, persistent decreases were observed in the T-lymphocyte subsets, whereas the absolute number of B lymphocytes had returned to levels near base line. T-cell proliferative responses at follow-up were not significantly different from entry values, except that the response to mitogenic anti-T11 (CD2) antibodies was decreased (P less than 0.01). Our data indicate that monthly intravenous administration of cyclophosphamide was associated with a substantial amelioration of severe systemic lupus, in conjunction with discrete changes in T-lymphocyte markers and T-cell function. This was a preliminary, uncontrolled study, but the results warrant further investigation of this form of treatment.
严重的系统性红斑狼疮累及肾脏或中枢神经系统时，即便使用大剂量皮质类固醇进行治疗，仍可能导致器官衰竭或死亡。为评估静脉注射环磷酰胺在此种情况下的临床及免疫学效果，我们对9例患者进行了为期6个月的每月一次静脉输注环磷酰胺的治疗。对入组时及随访时的各项特征进行比较发现（采用配对t检验），肌酐清除率有所改善（从每分钟66 ml提高至96 ml，P<0.001）；24小时尿蛋白水平（从4.11 g降至0.90 g，P<0.05），法尔抗DNA滴度（从43降至8.5%，P<0.01）；补体成分C3（从每升894 mg升至1150 mg，P<0.05），C4（从154 mg升至222 mg，P<0.05），以及总补体活性（CH50）（从88.7 IU升至113.4 IU，P<0.05）；以及魏氏血沉率（从每小时60.2 mm降至34.4 mm，P<0.0005）。多数情况下，狼疮的其他表现也有显著改善，尽管泼尼松的日均剂量从入组时的45 mg降至随访时的17 mg（P<0.01）。治疗期间，T3、T4、T8及B1阳性淋巴细胞数量逐渐减少。随访时，T淋巴细胞亚群持续减少，而B淋巴细胞的绝对数量已恢复至接近基线水平。随访时T细胞增殖反应与入组时相比无显著差异，只是对促有丝分裂抗T11（CD2）抗体的反应有所降低（P<0.01）。我们的数据表明，每月静脉注射环磷酰胺与严重系统性红斑狼疮的显著改善相关，同时T淋巴细胞标志物及T细胞功能也有离散性变化。这是一项初步的、非对照研究，但结果值得对这种治疗方式进行进一步研究。
