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系统性红斑狼疮患者接受环磷酰胺或吗替麦考酚酯治疗后免疫细胞频率的变化。

Changes in immune cell frequencies after cyclophosphamide or mycophenolate mofetil treatments in patients with systemic lupus erythematosus.

机构信息

Department of Rheumatology, First Hospital, Jilin University, Changchun, China.

出版信息

Clin Rheumatol. 2012 Jun;31(6):951-9. doi: 10.1007/s10067-012-1958-8. Epub 2012 Feb 21.

DOI:10.1007/s10067-012-1958-8
PMID:22349930
Abstract

This study was designed to explore the profile of immune cell subsets, including T, B, natural killer (NK), and NKT cells, in systemic lupus erythematosus (SLE) patients, and to determine their relationships with the clinical index and the effects of cyclophosphamide (CYC) and mycophenolate mofetil (MMF) treatment. SLE patients (n = 28) and age/sex-matched healthy controls (n = 28) were evaluated. The patients were equally divided into two treatment groups: intravenous drip (IVD) with CYC and prednisolone, and oral MMF and IVD with prednisolone. SLE peripheral blood samples were taken immediately prior to treatment and after 4 weeks of drug treatment. T, B, NK, and NKT cell subsets were measured by flow cytometry. Double-stranded DNA antibody and Sm antibody were detected by indirect immunofluorescence. Serum C3, C4, and C-reactive protein were determined by scatter turbidimetry. The percentages of CD3+CD4+ T, CD3-CD16CD56+ NK, and CD3+CD16CD56+ NKT cells and the CD4+/CD8+ ratio were significantly lower in SLE patients, while CD3+CD8+ T and CD3-CD19+ B cells were higher than the controls. The lymphocyte subsets were significantly correlated with the SLE disease activity index (SLEDAI) and complement factors (C3, C4). Four weeks of CYC or MMF treatment led to a significant increase in CD3+CD4+ T cells (P < 0.05). In addition, both CYC and MMF treatments led to increases in CD3+ T and CD3-CD16CD56+NKT cells and decreases in CD3-CD16CD56+ NK and CD3+CD8+ T cells, but these changes were not obvious. The significant correlation that exists between lymphocytes subsets and SLEDAI activity scores suggests that the lymphocyte subsets may reflect SLE severity. Our results indicate that both the traditional cyclophosphamide agent and the new mycophenolate mofetil agent can regulate the lymphocyte subsets and consequent abnormal immunity, suggesting that MMF, which is known to produce less side-effects than CYC, may be used as an effective treatment of SLE.

摘要

这项研究旨在探讨系统性红斑狼疮(SLE)患者免疫细胞亚群的特征,包括 T、B、自然杀伤(NK)和 NKT 细胞,并确定它们与临床指标的关系,以及环磷酰胺(CYC)和霉酚酸酯(MMF)治疗的影响。评估了 28 例 SLE 患者和 28 名年龄和性别匹配的健康对照者。患者分为两组:静脉滴注(IVD)CYC 和泼尼松龙,以及口服 MMF 和 IVD 泼尼松龙。在治疗前和药物治疗 4 周后采集 SLE 外周血样本。通过流式细胞术测量 T、B、NK 和 NKT 细胞亚群。通过间接免疫荧光法检测双链 DNA 抗体和 Sm 抗体。通过散射比浊法测定血清 C3、C4 和 C 反应蛋白。SLE 患者 CD3+CD4+T、CD3-CD16CD56+NK 和 CD3+CD16CD56+NKT 细胞的百分比以及 CD4+/CD8+比值明显低于对照组,而 CD3+CD8+T 和 CD3-CD19+B 细胞则高于对照组。淋巴细胞亚群与 SLE 疾病活动指数(SLEDAI)和补体因子(C3、C4)显著相关。CYC 或 MMF 治疗 4 周后,CD3+CD4+T 细胞显著增加(P<0.05)。此外,CYC 和 MMF 治疗均导致 CD3+T 和 CD3-CD16CD56+NKT 细胞增加,CD3-CD16CD56+NK 和 CD3+CD8+T 细胞减少,但这些变化不明显。淋巴细胞亚群与 SLEDAI 活动评分之间存在显著相关性,表明淋巴细胞亚群可能反映 SLE 的严重程度。我们的研究结果表明,传统的环磷酰胺药物和新的霉酚酸酯药物都可以调节淋巴细胞亚群和随之而来的异常免疫,这表明霉酚酸酯可能作为一种有效的 SLE 治疗药物,其副作用比环磷酰胺少。

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