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Abstract: TH-PO819

Activation of Toll Like Receptors 7/8 Altered IgA1 O-Glycosylation via Regulating Expression of O-Glycosyltransferases in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Zheng, Nuoyan, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
  • Yu, Xueqing, Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Background

IgA nephropathy (IgAN) is featured with O-glycosylation deficiency of IgA1 antibody, but the underlying mechanism of production of Gd-IgA1 was unknown.

Methods

The expression levels of TLRs were analyzed by real-time PCR. The secretion of IgA1 molecules and their O-glycan after TLR activiation were meansured by ELISA. The expression of O-glycosyltransferases was analyzed by Western blot.

Results

We found that gene expression levels of TLR7 and TLR8 were significantly increased in peripheral blood mononuclear cells (PBMCs) of IgAN patients (Figure 1A). Ex-vivo activation of TLR7/8 in PBMCs led to more IgA1 antibody production and higher O-glycan deficiency of IgA1 antibody in IgAN patients as compared with healthy donors (Figure 1B). Meanwhile, activation of TLR7/8 resulted in decreased expression C1GalT1 and increased GalNAcT2 expression in B cells of IgAN patients (Figure 2).

Conclusion

Thus, activation of TLR7/8 play important role in pathogenesis of IgA nephropathy by regulating the expression of O-glycosyltransferase and later the galactose deficiency of IgA molecules.

Figure 1-TLR7/8 activation led to augmented IgA1 secretion and galactose deficiency

Figure 2-TLR7/8 activation regulates expression of O-glycosyltransferases.