Tselios Konstantinos, Sarantopoulos Alexandros, Gkougkourelas Ioannis, Papagianni Aikaterini, Boura Panagiota
Clinical Immunology Unit, 2nd Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Int J Rheum Dis. 2014 Sep;17(7):790-5. doi: 10.1111/1756-185X.12500.
Cyclophosphamide efficacy in lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE) is probably mediated by a non-specific ablation of reactive lymphocytes. However, little is known in regard to its effect on T regulatory cells (Tregs) in such patients, which was the aim of this study.
Ten Caucasian lupus patients were included, six with LN classes IV-V (mean age 33.8 ± 8.8 years) and four with NPSLE (mean age 35.5 ± 8.8 years, clinical manifestations: 1/4 acute confusional state, 1/4 psychosis, 2/4 refractory seizures). Cyclophosphamide was administered at monthly pulses (500 mg/m(2) /month for 6 months); doses of other administered drugs, including steroids, remained stable or lower. CD4(+) CD25(high) FOXP3(+) Tregs were assessed by flow-cytometry at baseline and before every subsequent pulse and 3-6 months after the final pulse. Disease activity was assessed by SLE Disease Activity Index (SLEDAI).
In LN patients, Tregs were significantly increased even after the fourth pulse (0.54 ± 0.20% vs. 1.24 ± 0.29%, P < 0.001). Likewise, in NPSLE, Tregs were significantly expanded after the fourth pulse (0.57 ± 0.23% vs. 1.41 ± 0.28%, P < 0.001). SLEDAI was significantly reduced in all patients.
Cyclophosphamide pulse therapy was associated with a significant increase of the CD4(+) CD25(high) FOXP3(+) Tregs in patients with active LN and NPSLE. This effect is probably indirect and may partially explain the beneficial role of cyclophosphamide in such cases.
环磷酰胺在狼疮性肾炎（LN）和神经精神性系统性红斑狼疮（NPSLE）中的疗效可能是通过对反应性淋巴细胞的非特异性清除介导的。然而，关于其对此类患者调节性T细胞（Tregs）的影响知之甚少，这也是本研究的目的。
纳入10名白种人狼疮患者，6名LN IV - V级患者（平均年龄33.8 ± 8.8岁）和4名NPSLE患者（平均年龄35.5 ± 8.8岁，临床表现：1/4为急性意识模糊状态，1/4为精神病，2/4为难治性癫痫）。环磷酰胺每月脉冲给药（500 mg/m²/月，共6个月）；其他给药药物（包括类固醇）的剂量保持稳定或降低。在基线时、每次后续脉冲前以及最后一次脉冲后3 - 6个月通过流式细胞术评估CD4⁺CD25⁺高表达FOXP3⁺调节性T细胞。通过SLE疾病活动指数（SLEDAI）评估疾病活动度。
在LN患者中，即使在第四次脉冲后调节性T细胞也显著增加（0.54 ± 0.20%对1.24 ± 0.29%，P < 0.001）。同样，在NPSLE患者中，第四次脉冲后调节性T细胞显著增多（0.57 ± 0.23%对1.41 ± 0.28%，P < 0.001）。所有患者的SLEDAI均显著降低。
环磷酰胺脉冲治疗与活动性LN和NPSLE患者CD4⁺CD25⁺高表达FOXP3⁺调节性T细胞显著增加有关。这种作用可能是间接的，并且可能部分解释了环磷酰胺在此类病例中的有益作用。
