Abnormalities of glycogenes in tonsillar lymphocytes in IgA nephropathy

Abstract

Glycosylation, which represents the most complex post-translational modification, plays a pivotal role during protein maturation, and is orchestrated by numerous glycosyltransferases. Aberrant O-glycosylation of serum and tonsillar IgA1 is presumed to be one of the pathogeneses of IgA nephropathy (IgAN). However, the synthesis of underglycosylated IgA1 in tonsils has not yet been characterized. This study investigated tonsillar B lymphocytes of IgAN using tonsils from patients with chronic tonsillitis and sleep apnea syndrome. Gene expression of β1,3-galactosyltransferase (β3GalT), Cosmc, UDP-N-acetyl-α-D-galactosamine: polypeptide N-acetylgalactosaminyl-transferase 2, were significantly down regulated in tonsillar CD19-positive B lymphocytes from IgAN patients compared to control as determined by real-time RT-PCR. In contrast, the level of sialyltransferase was not significantly different among the three groups. Tonsillar B cell β3GalT gene expression significantly correlated with estimated GFR and negatively correlated with proteinuria and glomerular or interstitial injury score. Double immunofluorescent staining showed that some IgA-positive cells in the intrafollicular area were also positive for β3GalT staining. Western blotting showed the protein expression of β3GalT in the tonsils to significantly decrease in IgAN in comparison to the controls. These data suggest the downregulation of β3GalT in tonsillar B lymphocytes to be closely associated with the clinical characteristics of IgAN.