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利妥昔单抗调节激素依赖性肾病综合征患者的 T 淋巴细胞亚群和 B 淋巴细胞亚群及尿 CD80 排泄。

Rituximab modulates T- and B-lymphocyte subsets and urinary CD80 excretion in patients with steroid-dependent nephrotic syndrome.

机构信息

Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Pediatric Biology Center, Translational Health Science & Technology Institute, Faridabad, India.

出版信息

Pediatr Res. 2018 Oct;84(4):520-526. doi: 10.1038/s41390-018-0088-7. Epub 2018 Jul 9.

Abstract

BACKGROUND

Rituximab, a monoclonal antibody targeting B lymphocytes, effectively sustains remission in steroid-dependent nephrotic syndrome (SDNS). We studied its effects on lymphocyte subsets and urinary CD80 excretion (uCD80) in patients with SDNS.

METHODS

Blood and urine samples were collected from 18 SDNS patients before rituximab, and after 1 month and 1 year or at first relapse. T and B lymphocytes and uCD80 were determined by flow cytometry and ELISA, respectively.

RESULTS

Treatment was associated with reduction in counts of Th17, Th2, and memory T cells, and increased T-regulatory (Treg) cells. The Th17/Treg ratio declined from baseline (median 0.6) to 1 month (0.2, P = 0.006) and increased during relapse (0.3, P = 0.016). Ratios of Th1/Th2 cells at baseline, 1 month after rituximab, and during relapse were 7.7, 14.0 (P = 0.0102), and 8.7, respectively. uCD80 decreased 1 month following rituximab (45.5 vs. 23.0 ng/g creatinine; P = 0.0039). B lymphocytes recovered earlier in relapsers (60.0 vs.183.0 days; P < 0.001). Memory B cells were higher during relapse than remission (29.7 vs.18.0 cells/µL; P = 0.029).

CONCLUSION

Rituximab-induced sustained remission and B-cell depletion was associated with reduced numbers of Th17 and Th2 lymphocytes, and increased Treg cells; these changes reversed during relapses. Recovery of B cells and memory B cells predicted the occurrence of a relapse.

摘要

背景

靶向 B 淋巴细胞的单克隆抗体利妥昔单抗可有效维持激素依赖性肾病综合征(SDNS)患者的缓解。我们研究了它对 SDNS 患者淋巴细胞亚群和尿 CD80 排泄(uCD80)的影响。

方法

从 18 例 SDNS 患者中采集血液和尿液样本,分别在利妥昔单抗治疗前、治疗后 1 个月和 1 年或首次复发时进行。通过流式细胞术和 ELISA 分别测定 T 和 B 淋巴细胞和 uCD80。

结果

治疗与 Th17、Th2 和记忆 T 细胞计数减少以及 T 调节(Treg)细胞增加有关。Th17/Treg 比值从基线(中位数 0.6)下降到 1 个月(0.2,P = 0.006),并在复发时增加(0.3,P = 0.016)。基线、利妥昔单抗治疗后 1 个月和复发时的 Th1/Th2 细胞比值分别为 7.7、14.0(P = 0.0102)和 8.7。利妥昔单抗治疗后 1 个月 uCD80 下降(45.5 与 23.0ng/g 肌酐;P = 0.0039)。复发者的 B 淋巴细胞更早恢复(60.0 与 183.0 天;P < 0.001)。记忆 B 细胞在复发时高于缓解期(29.7 与 18.0 个/μL;P = 0.029)。

结论

利妥昔单抗诱导的持续缓解和 B 细胞耗竭与 Th17 和 Th2 淋巴细胞数量减少以及 Treg 细胞增加有关;这些变化在复发时逆转。B 细胞和记忆 B 细胞的恢复预测了复发的发生。

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