【摘要】 目的 评估BCMA-CD19双靶点嵌合抗原受体T细胞(CAR-T)治疗在狼疮性肾炎(LN)患者中的长期疗效与安全性。方法 回顾性分析11例接受BCMA-CD19双靶点CAR-T细胞治疗的狼疮肾炎患者，中位随访30(30,33)个月，评估临床缓解率;对其中9例进行了重复肾活检的患者评估病理改变、活动指数(AI)和慢性指数(CI)变化趋势。结果 CAR-T细胞治疗后6个月，SLEDAI评分平均下降9.18分(P<0.001); 11例(100%)达到低疾病活动度(LLDAS)，其中6例(63.6%)达到系统性红斑狼疮缓解(DORIS);治疗后6个月、12个月、24个月及30个月间缓解情况比较，差异无统计学意义。重复肾活检显示免疫荧光强度降低，AI显著下降[ΔAI=(-1.67±0.52),P=0.01],CI呈升高趋势但差异无统计学意义(P=0.067)。所有患者随访期间未出现结核感染、肝炎病毒感染或恶性肿瘤。结论 BCMA-CD19双靶点CAR-T细胞治疗可在长达3年的随访中持续诱导难治性LN患者临床缓解，显著降低肾脏病理活动度，且安全性良好;但仍需开展更长时间以及更大样本量研究予以验证其长期疗效及机制。更多还原

【Abstract】 Objective To evaluate the long-term efficacy and safety of BCMA-CD19 compound chimeric antigen receptor T-cell( CAR-T) therapy in patients with lupus nephritis( LN). Methods Eleven refractory LN patients who received BCMA-CD19 compound CAR-T infusion were retrospectively analyzed. After a median follow-up of 30( IQR 30-33) months,clinical response rates were assessed. Nine patients underwent serial renal biopsies; changes in histopathology,activity index( AI) and chronicity index( CI) were compared with baseline. Results Six months post-infusion,mean SLEDAI-2K score fell from( 13. 5 ± 2. 3) to( 4. 3 ± 1. 6)( Δ =-9. 18; P < 0. 001). All 11 patients( 100 %) achieved low lupus disease activity state( LLDAS),and 7( 63. 6 %) met the DORIS remission criteria. Response rates remained stable at 12,24 and 30 months without significant fluctuation( P > 0. 05). Repeat biopsies revealed marked reduction in immunofluorescence intensity and a significant decrease in AI [ΔAI =(-1. 67 ± 0. 52),P = 0. 01],whereas CI showed a non-significant upward trend( P = 0. 067). No tuberculosis,hepatitis virus or malignancy was observed during follow-up. Conclusions BCMA-CD19 compound CAR-T therapy induces sustained clinical remission for up to 3 years in refractory LN,substantially attenuates renal pathological activity,and displays an acceptable safety profile. Larger studies with longer surveillance are warranted to confirm durability and elucidate underlying mechanisms.更多还原