自体造血干细胞移植联合间歇小剂量环磷酰胺治疗重型狼疮肾炎的疗效评估

Evaluation of the efficacy of autologous hematopoietic stem cell transplantation combined with intermittent low dose cyclophosphamide in the treatment of severe lupus nephritis

目的分析自体造血干细胞移植(autologous hemopoietic stem cell transplantation,ASCT)法联合间歇小剂量环磷酰胺治疗重型狼疮肾炎的疗效评估及对血清抗双链DNA(dsDNA)抗体、外周血单个核细胞(peripheral blood mononuclear cell,PBMC)蛋白质羰基浓度与Fas表达率的影响。方法将2016年1月至2018年1月间西安市第五医院收治的120例重型狼疮肾炎患者随机分为观察组及对照组;对照组采用ASCT法治疗,观察组采用ASCT法联合间歇小剂量环磷酰胺治疗;治疗前及治疗结束6个月收集两组系统性红斑狼疮疾病活动指数(systemic lupus erythematosus disease activity index,SLEDAI),检测两组患者尿中血红细胞数、尿蛋白、血白蛋白、血小板、抗U1核糖核蛋白(anti-U1 ribonucleoprotein,U1RNP)抗体、补体C3、外周血CD4^+T、CD8^+T、CD4^+/CD8^+比值、调节性T细胞(T regulatory cell,Treg)和CD20+B细胞百分率、抗dsDNA抗体、PBMC蛋白质羰基浓度、T细胞Fas表达率、B细胞Fas表达率及T、B淋巴细胞凋亡率。结果经过治疗后,观察组SLEDAI评分显著低于对照组(P<0.05),尿红细胞数、尿蛋白水平、血清抗dsDNA抗体、血清PBMC蛋白质羰基浓度、T细胞及B细胞的Fas表达率、T细胞及B细胞凋亡率显著低于对照组(P<0.05);观察组患者血白蛋白水平、血小板、C3、CD4^+、CD8^+、CD4^+/CD8^+、Treg、CD20^+B细胞水平均显著高于对照组(P<0.05);观察组患者U1RNP阳性率显著低于对照组(P<0.05)。结论采用ASCT法联合间歇小剂量环磷酰胺治疗重型狼疮肾炎后可有效提高临床疗效,并降低血清抗dsDNA抗体、PBMC蛋白质羰基浓度水平与Fas表达率。

Objective To evaluate the efficacy of autologous hemopoietic stem cell transplantation(ASCT)combined with intermittent low-dose cyclophosphamide in the treatment of severe lupus nephritis and its effect on serum anti-dsDNA antibody,PBMC protein carbonyl concentration and Fas expression rate.Methods 120 patients with severe lupus nephritis admitted to the Fifth Hospital of Xi’an from January 2016 to January 2018 were randomly divided into observation group and control group;the control group was treated with ASCT method,and the observation group was treated with ASCT method combined with intermittent small dose.Cyclophosphamide treatment;systemic lupus erythematosus disease activity index(SLEDAI)was collected before treatment and 6 months after treatment,and the number of erythrocytes,urine protein and albumin in urine were detected in the two groups,platelets,anti-U1 ribonucleoprotein(U1RNP)antibody,complement C3,peripheral blood CD4^+T,CD8^+T,CD4^+/CD8^+ratio,regulatory T cell(Treg),and CD20+B cell percentage,dsDNA antibody,PBMC protein carbonyl concentration,T cell Fas expression rate,B cell Fas expression rate and T,B lymphocyte apoptosis rate.Results After treatment,the SLEDAI score of the observation group was significantly lower than that of the control group(P<0.05),the number of urinary red blood cells,urine protein level,serum dsDNA antibody,serum PBMC protein carbonyl concentration,Fas expression rate of T cells and B cells,T cells and The apoptosis rate of B cells was significantly lower than that of the control group(P<0.05).The levels of serum albumin,platelet,C3,CD4^+,CD8^+,CD4^+/CD8^+,Treg and CD20+B cells in the observation group were significantly higher than those in the control group(P<0.05).The positive rate of U1RNP in the observation group was significantly lower than that in the control group(P<0.05).Conclusions The use of ASCT combined with intermittent low-dose cyclophosphamide in the treatment of severe lupus nephritis can effectively improve the clinical efficacy,and reduce serum anti-dsDNA antibody,PBMC protein carbonyl concentration level and Fas expression rate.