Bijl M, Horst G, Bootsma H, Limburg P C, Kallenberg C G M
Department of Clinical Immunology, University Hospital, Groningen, The Netherlands.
Ann Rheum Dis. 2003 Jun;62(6):534-9. doi: 10.1136/ard.62.6.534.
Systemic lupus erythematosus (SLE) is characterised by the presence of antibodies to double stranded DNA (dsDNA), which are involved in the pathogenesis of SLE. Previous studies showed that at least two thirds of patients develop a clinical relapse within six months after a significant rise in the anti-dsDNA level, and most relapses were prevented by the administration of corticosteroids at the time of the rise.
To determine whether mofetil mycophenolate (MMF) can prevent a clinical relapse without the side effects associated with corticosteroids.
36 patients with SLE were examined monthly to determine whether a rise in anti-dsDNA level had occurred. A rise was defined as an increase of 25% of the level of the previous sample of at least 15 IU/ml within a four month period. After a rise patients were treated with MMF 2000 mg daily for six months. Patients were monitored monthly for the occurrence of a clinical relapse and to assess the serological activity and state of activation of CD4+, CD8+, and CD19+ lymphocyte subsets.
Anti-dsDNA rose in 10 patients. Treatment with MMF was started in all these patients, and after six months no clinical relapse had occurred. Side effects were minimal. Antibodies to dsDNA decreased during the treatment (p<0.001), associated with a decrease in the state of activation of CD19+ lymphocytes. No changes were found in the state of activation of CD4+ or CD8+ lymphocyte subsets.
Administration of MMF after a rise in antibodies to dsDNA is well tolerated, decreases anti-dsDNA and B cell activation, and seems to prevent the occurrence of a clinical relapse in patients with SLE.
系统性红斑狼疮(SLE)的特征是存在双链DNA(dsDNA)抗体,这些抗体参与了SLE的发病机制。先前的研究表明,至少三分之二的患者在抗dsDNA水平显著升高后的六个月内会出现临床复发,并且大多数复发在升高时通过给予皮质类固醇得以预防。
确定霉酚酸酯(MMF)是否能够预防临床复发而无皮质类固醇相关的副作用。
每月对36例SLE患者进行检查,以确定抗dsDNA水平是否升高。升高定义为在四个月内较前一个样本水平增加25%或至少增加15 IU/ml。升高后,患者每日服用2000 mg MMF,持续六个月。每月监测患者临床复发的发生情况,并评估血清学活性以及CD4 +、CD8 +和CD19 +淋巴细胞亚群的活化状态。
10例患者抗dsDNA升高。所有这些患者均开始使用MMF治疗,六个月后未发生临床复发。副作用极小。治疗期间dsDNA抗体下降(p<0.001),与CD19 +淋巴细胞活化状态的下降相关。CD4 +或CD8 +淋巴细胞亚群的活化状态未发现变化。
dsDNA抗体升高后给予MMF耐受性良好,可降低抗dsDNA水平和B细胞活化,似乎能预防SLE患者临床复发的发生。