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

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.

Keywords: T-cell receptor repertoire; clinical response; high-throughput sequencing; membranous nephropathy; non-invasive biomarkers.