Background: Aberrant mucosal immune responses are underlying causes of Immunoglobulin A nephropathy (IgAN), the most prevalent type of chronic glomerulonephritis. However, the role of T cells in IgAN pathogenesis remains elusive. To address this knowledge gap, we profiled the T-cell receptor (TCR) repertoire in the tonsils of patients with IgAN. Methods: This study included 27 and 20 patients with biopsy-confirmed IgAN and recurrent tonsillitis (RT), respectively, who underwent tonsillectomy. The TCR repertoire was determined by high-throughput sequencing coupled with unbiased adaptor ligation polymerase chain reaction (PCR). Furthermore, the usage of variable and joining regions in TCRα (TRA) and β (TRB) genes in each group was assessed. TRA clonotypes shared among the patients were characterized by complementary determining region 3 (CDR3) lengths, types of mucosal-associated invariant T (MAIT) cells, hydrophobicity, and their relationships with tonsillar galactose-deficient IgA1 (Gd-IgA1) and tonsillar IgA-binding indices of tonsillar bacteria. Results: The TRA repertoire exhibited significantly lower similarity in patients with IgAN than did in RT cases (P < 0. 001). Sharing TRA clonotypes among patients with IgAN was significantly sparser than that among RT cases. The relative abundance of shared TRA clonotypes with shorter CDR3 lengths was significantly increased in patients with IgAN (Pₐdj = 0. 041), which was characterized by low MAIT match scores. Significant negative correlations were observed between the MAIT scores and hydrophobicity for these TRA clonotypes in patients with IgAN. The relative abundances of these clonotypes significantly and positively correlated with the IgA binding indices of the phylum Bacteroidetes (Pₐdj = 0. 008) in both groups and tonsillar Gd-IgA1 levels in patients with IgAN (P = 0. 035). Conclusions: The results in this study suggest aberrant T-cell subsets involvement in tonsillar immunity in patients with IgAN.
Satokata et al. (Tue,) studied this question.