Increased levels of IgA and IgA deposition in kidney glomeruli of influenza infected ST6Gal I deficient mice (93.38)

Abstract

Abstract ST6Gal I, a glycosyltransferase highly expressed by B cells, catalyzes the addition of alpha-2, 6 sialic acid to galactose (Siaα2-6Gal), a modification found on N-linked glycoproteins. Aberrant glycosylation has been associated with the pathogenesis of IgA nephropathy (IgAN), a disease characterized by immune complex deposits in the glomerular mesangium, which can lead to end-stage renal failure in 20-40% of diagnosed patients. Previously, we have shown that ST6Gal I-/- mice infected with influenza A/HKx31 demonstrated profound impairment in the generation of viral-specific humoral responses, although memory IgG responses were mostly normal. We now show that influenza infected ST6Gal I-/- mice had higher levels of influenza-specific IgA and total IgA in sera at memory compared to WT mice. Additionally, we observed increased deposition of IgA in the glomeruli of kidneys of ST6Gal I-/- mice, although no differences were noted in urinalysis. These data suggest that loss of expression of an alpha-2,6 sialyltransferase, together with influenza viral infection, can contribute to increased deposition of IgA in mouse kidney glomeruli, and may contribute to the pathogenesis of one of the most common forms of glomerulonephritis in humans.