Characterization of T-Cell receptor repertoire in immunoglobulin a nephropathy

Abstract

Abstract Immunoglobulin A nephropathy (IgAN) is an autoimmune disease characterized by abnormal IgA deposition in glomerulus. Current diagnosis of IgAN still depends on renal biopsy, an invasive method that might increase the risk of clinical outcomes. Therefore, we aimed to explore the characteristics of T cell repertoire in IgAN from peripheral blood samples for identifying innovative diagnostic biomarkers. Herein, we included 8 IgAN patients, 25 non-IgAN patients, and 10 healthy controls in the study. A high-throughput immune repertoire sequencing was conducted to investigate the T-cell receptor beta-chain (TCRβ) repertoire of peripheral blood. Characteristics of TCRβ repertoire were assessed for these three distinct groups. A reduced TCRβ repertoire diversity was observed in IgAN patients compared to non-IgAN and healthy individuals. A skewed distribution toward shorter TCRβ complementarity determining region (CDR3) length was found in non-IgAN relative to IgAN patients. In addition, the differences in usages of five TRBV genes (TRBV5-4, TRBV6-4, TRBV12-1, TRBV16, and TRBV21-1) were identified between IgAN, non-IgAN, and healthy subjects. Of note, the TRBV6-4 gene, which is associated with mucosal-associated invariant T (MAIT) cells, exhibited higher usage in IgAN patients, suggesting potential importance of MAIT cells in IgAN. In short, our findings supported TCR repertoire characteristics as potential biomarkers for IgAN diagnosis.

Keywords

• Immunoglobulin A nephropathy (IgAN)
• T-cell receptor (TCR) repertoire
• TCR sequencing