The Landscape and Prognosis Potential of the T-Cell Repertoire in Membranous Nephropathy.

Yu Zhang,Xiaofen Liu,Lifang Zhang,Zuhui Su,Xiangping Chen,Huishi Li,Wei Luo,Zhanwen Guan,Yabin Jin,Yingming Pan,Yaozhong Kong,Peiyi Ye,Chao Xie

doi:10.3389/fimmu.2020.00387

Abstract

Membranous nephropathy (MN), a common pathological type of adult nephrotic syndrome, is an antibody-mediated kidney disease. It is widely accepted now that MN is an immune-related disease that involves the whole immune system. In this study, we analyzed the T-cell receptor beta chain (TCRβ) repertoire of the circulating T lymphocytes of MN patients and healthy controls using high-throughput sequencing. We compared multiple aspects of the TCRβ repertoire, including diversity and the Vβ and Jβ genes between MN patients and healthy controls, and we found that the diversities within the VJ cassette combination in the peripheral blood of MN patients were lower than in the healthy controls. We also found the TCRβ repertoire similarity between pre- and post-therapy could reflect the clinical outcome, and two Vβ genes in pre-therapy had the potential to predict the therapeutic effect. These findings indicated the potential of the TCRβ repertoire as non-invasive biomarkers for the prognosis prediction of MN. The characteristics of circulating T-lymphocyte repertoires shed light on MN detection, treatment, and surveillance.

Highlights

Membranous nephropathy (MN), a common pathological type of adult nephrotic syndrome, is an antibody-mediated kidney disease clinically characterized by proteinuria [1]
These findings indicated the potential of the TCRβ repertoire as non-invasive biomarkers for the prognosis prediction of MN
We compared multiple aspects of the TCRβ repertoire, including diversity and Vβ and Jβ genes between MN patients and healthy controls, and we found that the diversities of VJ cassette combination in peripheral blood of MN patients were lower than healthy controls

Summary

Introduction

Membranous nephropathy (MN), a common pathological type of adult nephrotic syndrome, is an antibody-mediated kidney disease clinically characterized by proteinuria [1]. The typical pathological characteristics are the deposition of immune complexes on the subepithelial side of the glomerular basement membrane (GBM), resulting in diffuse thickening of GBM [2, 3]. MN was regarded as an organ-specific autoimmune disease in which IgG autoantibodies form subepithelial immune complexes with autoantigens expressed on podocyte cell surfaces [2, 3]. The autoantibodies targeting phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were found in some MN patients [5, 6]. It is widely accepted that MN is an immune-related disease with the involvement of the whole immune system

Methods

Results

Conclusion