Shared T -Cell Receptor Repertoire in the Tonsils of Patients with IgA Nephropathy.

KEY POINTS: Patients with IgA nephropathy have significantly more abundant and shared joining regions in TCR α repertoires compared with those with recurrent tonsillitis. These are characterized by shorter complementary determining region 3 lengths and low mucosal-associated invariant T match scores. The clonotypes are correlated with the IgA-binding index of bacteroidetes and with tonsillar galactose-deficient IgA1 in these patients.

BACKGROUND

Aberrant mucosal immune responses are underlying causes of IgA nephropathy (IgAN), the most prevalent type of chronic GN. However, the role of T cells in IgA nephropathy pathogenesis remains elusive. To address this knowledge gap, we profiled the T -cell receptor repertoire in the tonsils of patients with IgA nephropathy.

METHODS

This study included 27 and 20 patients with biopsy-confirmed IgA nephropathy and recurrent tonsillitis (RT), respectively, who underwent tonsillectomy. The T -cell receptor (TCR) repertoire was determined by high-throughput sequencing coupled with unbiased adaptor ligation PCR. Furthermore, the usage of variable and joining regions in TCR α (TRA) and joining regions in TCR β (TRB) genes in each group was assessed. TRA clonotypes shared among the patients were characterized by complementary determining region 3 lengths, types of mucosal-associated invariant T (MAIT) cells, hydrophobicity, and their relationships with tonsillar galactose-deficient IgA1 and tonsillar IgA-binding indices of tonsillar bacteria.

RESULTS

The TRA repertoire exhibited significantly lower similarity in patients with IgA nephropathy than did in RT cases ( P < 0.001). Sharing TRA clonotypes among patients with IgA nephropathy was significantly sparser than that among RT cases. The relative abundance of shared TRA clonotypes with shorter complementary determining region 3 lengths was significantly increased in patients with IgA nephropathy ( P_adj = 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 IgA nephropathy. The relative abundances of these clonotypes significantly and positively correlated with the IgA binding indices of the phylum Bacteroidetes ( P_adj = 0.008) in both groups and tonsillar galactose-deficient IgA1 levels in patients with IgA nephropathy ( P = 0.035).

CONCLUSIONS

The results in this study suggest aberrant T -cell subsets involvement in tonsillar immunity in patients with IgA nephropathy.