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Abstract: TH-PO807

Immune Response to Tonsillar Microbiome Are Perturbed in the Development of IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Yamaguchi, Hiroki, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Goto, Shin, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Watanabe, Hirofumi, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Yonezawa, Masataka, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Yamamoto, Suguru, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Kaneko, Yoshikatsu, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Narita, Ichiei, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Background

The aberrant immune response in palatine tonsils against commensal bacteria has been estimated to be involved in the development of IgA nephropathy (IgAN). To elucidate these mechanisms, we focused on the relationship between the expression of TNFSF13 (APRIL) and galactose-deficient IgA1 (Gd-IgA1) and the composition of bacteria in tonsillar crypts.

Methods

We enrolled 57 patients with IgAN and 27 with recurrent tonsillitis (RT) who were undergone tonsillectomy. Genomic DNA were extracted from the excised tissues of tonsillar crypts in each patient and V4 regions of the 16S-ribosomal RNA gene sequence were applied to assess the relative abundance of bacteria. These tissues were also solubilized with a lysis buffer and the concentration of extracted proteins were quantified with BCA methods. The levels of APRIL and Gd-IgA1 in tonsils or serum were measured by ELISA, and the degree of Gd-IgA1 deposition in glomerulus were evaluated by immunohistochemical analysis. We analyzed the correlations between the levels of APRIL, Gd-IgA1 and bacterial abundance, as well as the grade of glomerular injury.

Results

Immunohistochemical analysis revealed that Gd-IgA1 was localized in germinal center of tonsils and the degree of its stained area was correlated with tonsillar Gd-IgA1 levels. The degree of Gd-IgA1 deposition in glomerulus was significantly correlated with tonsillar Gd-IgA1 levels. The levels of Gd-IgA1 in tonsil were significantly higher in IgAN patients with more extended glomerular damage, while tonsillar Gd-IgA1 levels in IgAN patients did not differ from those in RT patients.
Tonsillar APRIL levels were significantly higher in IgAN patients than in RT patients (P < 0.01). The levels of tonsillar APRIL in RT were positively correlated with the relative abundance of Prevotella genus in tonsils, however, the upregulated levels of tonsillar APRIL in IgAN did not show any robust associations with 16S microbiota in tonsils.

Conclusion

Gd-IgA1 and increased APRIL expression in tonsils could be involved in the development of IgAN. Further analysis is needed to reveal the role of microbiome on the mucosal immunity in tonsils of patients with IgAN.