CAJ | 학술논문

目的观察免疫吸附联合非清髓性化疗结合CD34+细胞分选的自体外周血干细胞移植治疗难治性SLE的疗效.方法难治性SLE 3例,均经肾活检确诊为狼疮性肾炎Ⅳ型,狼疮处于活动期,病情进展,常规治疗无效;应用以葡萄球菌A蛋白作为免疫吸附剂的吸附柱进行免疫吸附,一个疗程共6次,每次吸附血浆3 L;随后采用异环磷酰胺加重组人粒细胞集落刺激因子动员、Baxter CS-3000血细胞分离机采集外周血,获取单一核细胞,通过CD34+细胞分选仪分别得到2.6×106/kg、2.1×106/kg、2.4×106/kgCD34+细胞,采集物中分别含3×105/kg、2.1×105/kg、2.0×105/kg CD3+细胞,预处理为回输前6 d,每日应用氟达拉滨50 mg/d 共5 d,回输前3 d始每日应用抗胸腺细胞球蛋白90 mg/kg共5 d.结果 ①3例患者吸附后血浆中抗dsDNA、ANA抗体、lgG均明显下降,补体C3明显卜升.②3例患者均于移植后2～3 d获得造血重建.③移植后3例患者临床症状均明显缓解.SLEDAI评分均<3分.④移植后6个月,患者血浆中抗dsDNA、ANA抗体均转阴性,补体C3升至正常,尿蛋白转阴性,肾功能恢复正常.结论移植治疗难治性SLE近期疗效满意.
목적 관찰면역흡부연합비청수성화료결합CD34+세포분선적자체외주혈간세포이식치료난치성SLE적료효.방법 난치성SLE 3례,균경신활검학진위랑창성신염Ⅳ형,랑창처우활동기,병정진전,상규치료무효;응용이포도구균A단백작위면역흡부제적흡부주진행면역흡부,일개료정공6차,매차흡부혈장3 L;수후채용이배린선알가중조인립세포집락자격인자동원、Baxter CS-3000혈세포분리궤채집외주혈,획취단일핵세포,통과CD34+세포분선의분별득도2.6×106/kg、2.1×106/kg、2.4×106/kgCD34+세포,채집물중분별함3×105/kg、2.1×105/kg、2.0×105/kg CD3+세포,예처리위회수전6 d,매일응용불체랍빈50 mg/d 공5 d,회수전3 d시매일응용항흉선세포구단백90 mg/kg공5 d.결과 ①3례환자흡부후혈장중항dsDNA、ANA항체、lgG균명현하강,보체C3명현복승.②3례환자균우이식후2～3 d획득조혈중건.③이식후3례환자림상증상균명현완해.SLEDAI평분균<3분.④이식후6개월,환자혈장중항dsDNA、ANA항체균전음성,보체C3승지정상,뇨단백전음성,신공능회복정상.결론 이식치료난치성SLE근기료효만의.
Objective To observe the clinical efficacy of staphylococcal protein A immunoadsorption plus nonmyeloablative chemotherapy with CD34+ autologous peripheral blood stem cell transplantation in the treatment of refractory systemic lupus erythematosus (SLE). Methods Three patients with active SLE were enrolled into this study. All patients were diagnosed with lupus nephritis by renal biopsy and poorly responded to routine therapy. Before transplantation, patients were given 6 sessions of immunoadsorption apheresis using columns of staphylococcal protein A-silica with an interval of 3 days; each session processed 3 L plasma and a total of 18 L plasma was processed over the 6 treatments. Three days following the immunoadsorption apheresis, the mobilization of stem cells was realized by intravenous cyclophosphamide at a dose of 2 g per square meter of body surface area and subcutaneous recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 5 g per kilogram of body weight per day for 5 days. Then, peripheral blood raonoclonal cells were obtained by CS-3000 Cell Separator, and passed through the Clini Macs CD34+ cell selection device, with the final concentration of CD34+ cells being 2.6×106, 2.1×106 and 2.4×106 per kilogram of body weight respectively, and that of CD3+ cells being 3×105, 2.1×105, and 2.0×105 per kilogram of body weight, respectively, in these three patients. The conditioning regimen consisted of oral fludarabine of 50 mg/d for 5 days plus intravenous pig anti-human thymocyte immunoglobulin (ATG) at a daily dose of 90 mg/kg for 5 days. After 72-hour treatment with ATG, the frozen stem cells were infused back to the patients. Clinical manifestations and lupus-correlated immune parameters were compared in patients at baseline and after transplantation. Results Following immunoadsorption apheresis, an obvious decrease was observed in the level of serum anti-dsDNA, antinuclear antibody and IgG antibodies, while an increase in the level of serum complement 3. All patients achieved the reconstruction of hemopoiesis 2-3 days after the transplantation. Also, an apparent clinical remission was achieved with the SLEDAI score being less than 3. Six months after the transplantation, serum anti-dsDNA and antinuclear antibodies as well as urine protein were undetectable, the level of complement 3 reached the normal range, and renal function was restored. Conclusions Staphylococcal protein A immunoadsorption plus nonmyeloablative CD34+ autologous peripheral blood stem cell transplantation are effective and safe for refractory SLE, but the long-term effect remains to be connfirmed by further studies.