自体造血干细胞移植治疗狼疮性肾炎外周血淋巴细胞亚群的变化与临床疗效

Lymphocyte subset changes in patients with lupus nephritis after autologous hematopoietic stem cell transplantation

目的:探讨自体造血干细胞移植(ASCT)治疗顽固性狼疮性肾炎(LN)外周血淋巴细胞亚群的变化及其与临床疗效的关系。方法:选取2011年6月至2014年6月间18例经免疫抑制治疗未缓解或反复复发的顽固性LN患者接受ASCT治疗。环磷酰胺(CTX)联合粒细胞集落刺激因子行干细胞动员,CTX联合抗胸腺球蛋白多克隆抗体预处理。观察ASCT治疗后外周血CD4^+T、CD8^+T、CD4^+/CD8^+比值、调节性T细胞(CD4^+CD25^+Treg)和CD20^+B细胞的变化及其与临床疗效的关系。结果:ASCT治疗后系统性红斑狼疮疾病活动指数(SLEDAI)、尿蛋白和自身抗体阳性率显著下降,血清白蛋白和补体水平显著升高。采集后,患者CD4^+T细胞计数及CD8^+T细胞计数显著下降,回输后出现上升,回输后12个月、18个月CD4^+T细胞计数高于采集前,各时间点CD8^+T细胞计数均高于采集前;回输后CD4^+/CD8^+比值持续倒置,患者CD4^+CD25^+Treg计数显著增加。采集后,患者CD20^+B细胞计数显著下降,回输后快速增加。结论:ASCT治疗顽固性狼疮性肾炎有显著疗效,但淋巴细胞亚群失衡持续存在,CD4^+CD25^+Treg计数增加可能在治疗中发挥重要作用;6个月后CD20^+B细胞增加伴随自身抗体水平升高,表明抗B细胞治疗的必要性。

Objective： To observe the change of lymphocyte subsets in patients with severe lupus nephritis（ LN）after the autologous hematopoietic stem cell transplantation（ ASCT） and the relationship with clinical curative effect.Methodology： Eighteen patients with severe and refractory LN who underwent ASCT from June 2011 to June 2014 were investigated retrospectively,whose clinical manifestations persisted or recurred frequently after immunosuppressive therapy.Cyclophosphamide（ CTX） and granulocyte colony-stimulating factor（ G-CSF） were used before stem cell harvest,and the conditioning regimens included CTX and anti- thymocyte globulin（ ATG）. The therapeutic effect of ASCT on LN,as well as changes in CD4^＋T cells,CD8^＋T cells,CD4^＋CD25^＋regulatory T cells（ CD4 ＋ CD25^＋Treg） and CD20^＋B cells were analyzed. Results： After ASCT,the patients＇ SLE disease activity index（ SLE-DAI）,urine protein excretion,as well as autoantibody positive rate was decreased significantly,while the levels of serum albumin,C3 and C4 were increased notably. The counts of CD4^＋T cell and CD8^＋T cell were decreased after stem cell harvest,and then increased after transfusion. More CD4^＋T cells were found at 12 months、18 months after transfusion compared with before harvest,and more CD8^＋T cells were found every time point after transfusion compared with before harvest. The inversion of the CD4^＋/CD8^＋ratio persisted. The counts of CD4^＋CD25^＋Treg were increased notably after the treatment. The variation trend of CD20 ＋ B cells was the same as CD4^＋T cells and CD8^＋T cells. Conclusion： ASCT is an effective therapy to severe and refractory LN,but the imbalance of lymphocyte subsets persists. The increase of CD4^＋CD25^＋Treg counts may play an important role in the treatment. 6 months after transfusion,the number of CD20^＋B cells were increased,as well as the positive rate of autoantibodies. This suggests that it may be necessary to give immunosuppressive therapy at that time.