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Abstract: SA-PO640

T-Cell Receptor Repertoire Analysis in Tonsillar Tissues of Patients With IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Satokata, Kazunori, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Goto, Shin, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Yamaguchi, Hiroki, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Watanabe, Hirofumi, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Yamamoto, Suguru, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Kaneko, Yoshikatsu, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Narita, Ichiei, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Background

Immunoglobulin A nephropathy (IgAN) is the most prevalent primary chronic glomerulonephritis. The aberrant mucosal immune response is considered to be related to the IgAN pathogenesis. However, evidence for the involvement of T-cells in mucosal immunity of IgAN is limited, and we conducted a comprehensive analysis of T-cell receptor repertoire in the tonsillar tissues in patients with IgAN.

Methods

28 patients with biopsy-proven IgAN and 20 patients with recurrent tonsillitis (RT) who had undergone tonsillectomy were included in the study. After total RNA was extracted from each dissected tonsillar crypt, unbiased adaptor-ligation-PCR was carried out as library preparation. Then T cell receptor (TCR) sequencing was performed by the next-generation sequencer. We examined the usages of variable and joining regions and analyzed diversity and similarity in TCRα (TRA) and β (TRB) genes at the tonsillar crypts using bioinformatics software.

Results

TCR sequencing obtained an average of 74,761 in-frame reads in TRA gene and 57,163 in TRB gene per sample. Diversity indexes of repertoire in both TRA and TRB were not different between patients with IgAN and RT. Similarity indexes of TRA repertoire, but not TRB, were significantly lower in IgAN than in RT patients (p<0.01), and the sharing of TRA clonotypes by more than two individuals was significantly lower in IgAN patients (p<0.05). In shared TRA sequences, TRAV1-2 and TRAJ33, which belong to invariant TCRs, were significantly shared by RT patients (p<0.01). On the other hand, the relative abundance of shared TRA repertoires in IgAN patients was higher than in RT and significantly increased in shorter CDR3 lengths (p<0.05). TRAV41 was significantly abundant in shorter CDR3 lengths of IgAN patients.

Conclusion

Our data suggests that dynamic changes in the T-cell subset are involved in abnormal mucosal immune responses in the tonsils of patients with IgAN.