Rituximab Induces Complete Remission of Proteinuria in a Patient With Minimal Change Disease and No Detectable B Cells

TY - JOUR

T1 - Rituximab Induces Complete Remission of Proteinuria in a Patient With Minimal Change Disease and No Detectable B Cells

AU - Webendörfer, Maximilian

AU - Reinhard, Linda

AU - Stahl, Rolf A K

AU - Wiech, Thorsten

AU - Mittrücker, Hans-Willi

AU - Harendza, Sigrid

AU - Hoxha, Elion

N1 - Copyright © 2021 Webendörfer, Reinhard, Stahl, Wiech, Mittrücker, Harendza and Hoxha.

PY - 2021/2/8

Y1 - 2021/2/8

N2 - 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.

AB - 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.

U2 - 10.3389/fimmu.2020.586012

DO - 10.3389/fimmu.2020.586012

M3 - SCORING: Journal article

C2 - 33628202

VL - 11

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

M1 - 586012

ER -