系统性红斑狼疮非清髓性自体外周血造血干细胞移植后免疫重建的五年随访

Immune reconstitution after nonmyeloablative autologous peripheral blood stem cell transplantation for systemic lupus erythematosus 5-year follow-up

【摘要】目的探讨非清髓性自体外周血造血干细胞移植（NAST）治疗sLE后的免疫重建规律。方法总结10例接受NAST的SLE患者移植后的随访情况。动员方案为异环磷酰胺（IFO）＋粒细胞集落刺激因子（G—CSF）。非清髓性预处理方案：移植前1～2d，阿糖胞苻（200mg·kg-1·d-1）加环磷酰胺（40mg·kg-1·d-1）。应用流式细胞学技术分别于动员前、动员后，移植后2周及1、2、3、6、12、24、36、48及60个月监测患者体内的T细胞（CD3＋）、B细胞（CDl9＋）、NK细胞（CD3一CDl6’CD56＋）、Th细胞（CD3CD4＋）、Tc细胞（CD3＋CD8＋）、调节性T细胞（CD4＋CD25＋）和CD4／CD8＋比值的变化。采用t检验进行统计学分析。结果CD3＋细胞动员前为（1232＋354）／ram3，12个月后恢复正常。CD4＋细胞动员前为（602224）／mm3，移植后48个月恢复正常。CD8＋细胞动员前为（404215）／m，n3，移植后2个月恢复正常。CDl6＋CD56＋细胞动员前为（115＋38）／ram3，移植后36个月恢复正常。CDl9＋细胞动员前为（43±11）／ram3，移植后6个月恢复正常。CD4＋CD25＋细胞动员前为（6．9±1．4）／mm3，移植后24个门趋于稳定。CD8＋T细胞恢复早于CD4＋T细胞，CD4＋／CD8＋持续降低，移植7个月后逐渐回升。B细胞在移植后10个月恢复至正常。NK细胞移植后24个月恢复至正常并保持稳定。调节性T细胞与CD4＋细胞比值（CD4‘CD257CD4＋）移植后逐渐增加。结论NAST可以使难治性SLE患者病情明显缓解，监测移植后外用淋巴细胞、T细胞亚群、B细胞、NK细胞、调节性T细胞可评定疾病预后并可能早期预判复发。SLE患者行NAST后是否复发尚需进一步随访。

Objective To investigate the immunological reconstitution after non-myeloablative autologous peripheral blood stem cell transplantation （NAST） in patients with systemic lupus erythematosus （SLE）. Methods Summarized the outcomes of l0 patients with SLE after NAST. These patients received non-myeloablative conditioning regimen： mobilization with ifosfamide （IF（）） and colony-stimulating factor, pre-treatment regimen was composed of eytarabine （Ara-c. 200 mg kg-1 d-1 ） alnt cyelophosphamide （CTX, 40 mg＇kg-t＇d-）. Flow cytomet analysis was used to monitor the level of T lymphocytes（CD3＋）, B lymphoeytes （CDI9＋ ）, NK cells （CD3-CD16＋CD56＋ ）, T helper cells （CD3 ＋CD4＋ ）, T suppressor cells （CD3 ＋CD8＋ ）, regulatory T cells （CD4CD25） and the ratio of CD4qCD8＋ cells before and aider mobilization and 1/2, 1, 2, 3, 6, 12, 24, 36, 48, 60months after transplantation. T test was used for statistical analysis. Results The count of CD3＋ cell befi）re mobilization was （ 1 232＋354）/mm, which returned to normal after 12 months. The count of CD4＋ cell before mobilization was （602＋224）/mm, returned to normal after 48 months. The count of CD8＋ cells before mobilization was （404＋215）/mm3, which returned to normal after 2 months. The count of CDI6＋CD56 cells beh）re mobilization was （115＋38）/mm3, which returned to normal after 36 months. The count of CDI9＋ cells before mobilization was （43_＋11 ）/mm, which returned to normal at 6 months. The countof CD19 cells before mobilization was （43＋11）/ram3, which returned to normal after 6 months. The count of CD4＋ CD25 cellsbefore mobilization was （6.9-＋1.4）/mm3, which returned to normal and remained stable after 24 months. Thetime of CD8＋ T cells recovery in the T subtypes was shorter than that of the CD4＋ subtypes. The ratio of CD4/CD8＋ continued to decline, gradually raised only until 7 months after transplantation. The level of B lymphocytes returned to normal until 10 months after transplantation. The level of NK cells returned to normal in 24 weeks after transplantation and kept stable. The ratio of CD4＋CD25＋/CD4＋ cells gradually increased after transplantation. Conclusion NAST has curative effect and can initiate a rapid hematopoietic reconstitution without complications in patients with SLE. Monitoring the level of lymphocytes, T subtypes, B lymphocytes, NK cells and regulatory T cells in the peripheral blood can predict the prognosis and the relapse.