Strategies Towards Antigen-Specific Treatments for Membranous Nephropathy

TY - JOUR

T1 - Strategies Towards Antigen-Specific Treatments for Membranous Nephropathy

AU - Köllner, Sarah M S

AU - Seifert, Larissa

AU - Zahner, Gunther

AU - Tomas, Nicola M

N1 - Copyright © 2022 Köllner, Seifert, Zahner and Tomas.

PY - 2022

Y1 - 2022

N2 - Membranous nephropathy (MN) is a rare but potentially severe autoimmune disease and a major cause of nephrotic syndrome in adults. Traditional treatments for patients with MN include steroids with alkylating agents such as cyclophosphamide or calcineurin inhibitors such as cyclosporine, which have an undesirable side effect profile. Newer therapies like rituximab, although superior to cyclosporine in maintaining disease remission, do not only affect pathogenic B or plasma cells, but also inhibit the production of protective antibodies and therefore the ability to fend off foreign organisms and to respond to vaccination. These are undesired effects of general B or plasma cell-targeted treatments. The discovery of several autoantigens in patients with MN offers the great opportunity for more specific treatment approaches. Indeed, such treatments were recently developed for other autoimmune diseases and tested in different preclinical models, and some are about to jump to clinical practice. As such treatments have enormous potential to enhance specificity, efficacy and compatibility also for MN, we will discuss two promising strategies in this perspective: The elimination of pathogenic antibodies through endogenous degradation systems and the depletion of pathogenic B cells through chimeric autoantibody receptor T cells.

AB - Membranous nephropathy (MN) is a rare but potentially severe autoimmune disease and a major cause of nephrotic syndrome in adults. Traditional treatments for patients with MN include steroids with alkylating agents such as cyclophosphamide or calcineurin inhibitors such as cyclosporine, which have an undesirable side effect profile. Newer therapies like rituximab, although superior to cyclosporine in maintaining disease remission, do not only affect pathogenic B or plasma cells, but also inhibit the production of protective antibodies and therefore the ability to fend off foreign organisms and to respond to vaccination. These are undesired effects of general B or plasma cell-targeted treatments. The discovery of several autoantigens in patients with MN offers the great opportunity for more specific treatment approaches. Indeed, such treatments were recently developed for other autoimmune diseases and tested in different preclinical models, and some are about to jump to clinical practice. As such treatments have enormous potential to enhance specificity, efficacy and compatibility also for MN, we will discuss two promising strategies in this perspective: The elimination of pathogenic antibodies through endogenous degradation systems and the depletion of pathogenic B cells through chimeric autoantibody receptor T cells.

KW - Animals

KW - Autoantibodies/immunology

KW - B-Lymphocytes/pathology

KW - Cyclosporine/therapeutic use

KW - Glomerulonephritis, Membranous/drug therapy

KW - Humans

KW - Immunosuppressive Agents/therapeutic use

KW - Remission Induction

KW - Rituximab/therapeutic use

U2 - 10.3389/fimmu.2022.822508

DO - 10.3389/fimmu.2022.822508

M3 - SCORING: Review article

C2 - 35185913

VL - 13

JO - FRONT IMMUNOL

JF - FRONT IMMUNOL

SN - 1664-3224

M1 - 822508

ER -