Webendörfer Maximilian, Reinhard Linda, Stahl Rolf A K, Wiech Thorsten, Mittrücker Hans-Willi, Harendza Sigrid, Hoxha Elion
III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Front Immunol. 2021 Feb 8;11:586012. doi: 10.3389/fimmu.2020.586012. eCollection 2020.
Minimal change disease (MCD) is a common cause of nephrotic syndrome. Treatment with steroids is usually effective, but frequent relapses are therapeutic challenges. The anti-CD20 antibody rituximab has shown promising results for treatment of steroid-sensitive nephrotic syndrome. Since predictive biomarkers for treatment efficacy and the accurate rituximab dosage for effective induction of remission are unknown, measurement of CD19 B cells in blood is often used as marker of successful B cell depletion and treatment efficacy. A male patient with relapsing MCD was successfully treated with rituximab, but developed relapse of proteinuria 1 year later, although no B cells were detectable in his blood. B and T cell populations in the patient's blood were analyzed before and after treatment with rituximab using FACS analysis. Rituximab binding to B and T cells were measured using Alexa Fluor 647 conjugated rituximab. We identified a population of CD20 CD19 cells in the patient's blood, which consisted mostly of CD20 CD3 T cells. Despite the absence of B cells in the blood, the patient was again treated with rituximab. He developed complete remission of proteinuria and depletion of CD20 T cells. In a control patient with relapsing MCD initial treatment with rituximab led to depletion of both CD20 B and T cells. Rituximab induces remission of proteinuria in patients with MCD even if circulating B cells are absent. CD20 T cells may play a role in the pathogenesis of MCD and might be a promising treatment target in patients with MCD.
微小病变病(MCD)是肾病综合征的常见病因。使用类固醇治疗通常有效,但频繁复发是治疗面临的挑战。抗CD20抗体利妥昔单抗在治疗类固醇敏感性肾病综合征方面已显示出有前景的结果。由于治疗效果的预测生物标志物以及有效诱导缓解所需的准确利妥昔单抗剂量尚不清楚,血液中CD19 B细胞的检测常被用作B细胞耗竭成功和治疗效果的标志物。一名复发性MCD男性患者接受利妥昔单抗治疗成功,但1年后出现蛋白尿复发,尽管其血液中未检测到B细胞。使用流式细胞术分析(FACS分析)在利妥昔单抗治疗前后对患者血液中的B细胞和T细胞群体进行了分析。使用Alexa Fluor 647偶联的利妥昔单抗测量利妥昔单抗与B细胞和T细胞的结合。我们在患者血液中鉴定出一群CD20⁺CD19⁻细胞,其主要由CD20⁺CD3⁺T细胞组成。尽管血液中没有B细胞,该患者再次接受利妥昔单抗治疗。他出现蛋白尿完全缓解且CD20⁺T细胞耗竭。在一名复发性MCD对照患者中,利妥昔单抗初始治疗导致CD20⁺B细胞和T细胞均耗竭。即使循环B细胞缺失,利妥昔单抗也能诱导MCD患者的蛋白尿缓解。CD20⁺T细胞可能在MCD的发病机制中起作用,并且可能是MCD患者有前景的治疗靶点。