Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan.
Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan.
Clin Exp Nephrol. 2023 Jul;27(7):622-630. doi: 10.1007/s10157-023-02343-z. Epub 2023 Apr 24.
Rituximab is a promising option for refractory idiopathic nephrotic syndrome. However, no simple predictive markers for relapse after rituximab have been established. To determine such markers, we investigated the relationship between CD4 + and CD8 + cell counts and relapse after rituximab administration.
We retrospectively investigated patients with refractory nephrotic syndrome who received rituximab followed by immunosuppressive as maintenance therapy. Patients were divided into no relapse in 2 years after rituximab treatment or relapse group. After rituximab treatment, CD4 + /CD8 + cell counts were measured monthly, at prednisolone discontinuation, and at B-lymphocyte recovery. To predict relapse, these cell counts were analyzed using receiver operating characteristic (ROC). Additionally, relapse-free survival was reevaluated based on the result of ROC analysis for 2 years.
Forty-eight patients (18 in the relapse group) were enrolled. At prednisolone discontinuation (52 days after rituximab treatment), the relapse-free group showed significantly lower cell counts than the relapse group (median CD4 + cell count: 686 vs. 942 cells/µL, p = 0.006; CD8 + : 613 vs. 812 cells/µL, p = 0.005). In the ROC analysis, CD4 + cell count > 938 cell/µL and CD8 + cell count > 660 cells/µL could predict relapse in 2 years (sensitivity, 56% and 83%; specificity, 87% and 70%). The patient group with both lower CD4 + and CD8 + cell counts showed significantly longer 50% relapse-free survival (1379 vs. 615 days, p < 0.001 and 1379 vs. 640 days, p < 0.001).
Lower CD4 + and CD8 + cell counts in the early phase after rituximab administration may predict a lower risk of relapse.
利妥昔单抗是治疗特发性肾病综合征的一种很有前途的选择。然而,尚未建立用于预测利妥昔单抗治疗后复发的简单预测标志物。为了确定这些标志物,我们研究了 CD4+和 CD8+细胞计数与利妥昔单抗治疗后复发之间的关系。
我们回顾性调查了接受利妥昔单抗治疗后接受免疫抑制维持治疗的难治性肾病综合征患者。患者分为利妥昔单抗治疗 2 年后无复发或复发组。利妥昔单抗治疗后,每月、停用泼尼松时和 B 淋巴细胞恢复时测量 CD4+/CD8+细胞计数。使用受试者工作特征(ROC)分析这些细胞计数以预测复发。此外,根据 ROC 分析结果重新评估 2 年无复发生存率。
共纳入 48 例患者(复发组 18 例)。停用泼尼松时(利妥昔单抗治疗后 52 天),无复发组的细胞计数明显低于复发组(中位数 CD4+细胞计数:686 与 942 个/µL,p=0.006;CD8+:613 与 812 个/µL,p=0.005)。在 ROC 分析中,CD4+细胞计数>938 个/µL 和 CD8+细胞计数>660 个/µL 可预测 2 年内复发(敏感性分别为 56%和 83%,特异性分别为 87%和 70%)。CD4+和 CD8+细胞计数均较低的患者组无复发生存率显著更长(50%:1379 与 615 天,p<0.001 和 1379 与 640 天,p<0.001)。
利妥昔单抗治疗后早期 CD4+和 CD8+细胞计数较低可能预示复发风险较低。