目的:原发性膜性肾病(PMN)是成人肾病综合征的最常见原因。利妥昔单抗单一疗法已成为PMN患者的一线治疗方法,但预测利妥昔单抗反应的潜在标志物尚不清楚.
方法:在这项单臂回顾性试点研究中,纳入48例未接受过免疫抑制治疗的PMN患者。所有患者均接受利妥昔单抗治疗,并随访至少6个月。主要终点是在6个月时实现完全或部分缓解。在基线时收集淋巴细胞亚群,1个月,3个月和6个月,以确定利妥昔单抗治疗PMN缓解的预后因素。
结果:共有58.3%的患者(28/48)获得缓解。较低的血清肌酐,更大的血清白蛋白,在基线时在肾活检中检测到更高的磷脂酶A2受体抗原,在缓解组中发现。经过多次调整,基线时自然杀伤(NK)细胞的百分比很高,尤其是≥15.7%,与缓解密切相关(相对危险度=1.62;95%CI,1.00-2.62;P=0.049),与无应答者相比,对利妥昔单抗有应答的患者在随访期间的NK细胞平均百分比更高.使用受试者工作特征曲线进行分析,表明基线时NK细胞百分比的预后价值,曲线下面积为0.716(95%CI,0.556-0.876;P=0.021)。
结论:这项回顾性试点研究的结果表明,尤其是≥15.7%,基线时NK细胞的数量可能预测利妥昔单抗治疗的反应。这些发现为设计更大规模的研究提供了基础,以测试NK细胞在接受利妥昔单抗治疗的PMN患者中的预测价值。
Primary membranous nephropathy (PMN) is the most frequent cause of nephrotic syndrome in adults. Rituximab monotherapy has emerged as a front-line treatment for patients with PMN, but potential markers for predicting the response to rituximab are unknown.
In this single-arm retrospective pilot study, 48 patients with PMN without previous immunosuppressive therapy were enrolled. All patients were treated with rituximab and were followed up for at least 6 months. The primary end point was the achievement of complete or partial remission at 6 months. The subsets of lymphocytes were collected at baseline, 1 month, 3 months and 6 months to identify prognostic factors for achieving remission of PMN with rituximab therapy.
A total of 58.3% of patients (28/48) achieved remission. Lower serum creatinine, greater serum albumin, and greater phospholipase A2 receptor antigen detected in kidney biopsy at baseline were found in the remission group. After multiple adjustments, a high percentage of natural killer (NK) cells at baseline, especially ≥15.7%, was strongly associated with remission (relative risk = 1.62; 95% CI, 1.00-2.62; P = 0.049), and patients with a response to rituximab had a greater mean percentage of NK cells during the follow-up period compared with nonresponders. Analysis using a receiver operating characteristic curve indicated prognostic value of the NK-cell percentage at baseline, with an area under the curve of 0.716 (95% CI, 0.556-0.876; P = 0.021).
The findings from this retrospective pilot study suggest that a high percentage, especially ≥15.7%, of NK cells at baseline might predict a response to rituximab treatment. These findings provide a basis for designing larger-scale studies to test the predictive value of NK cells in patients with PMN undergoing rituximab treatment.