IgA1 molecules produced by tonsillar lymphocytes are under-O-glycosylated in IgA nephropathy

Abstract

Background: Human serum immunoglobulin A1 (IgA1) has a unique mucine-like structure in its hinge region that contains O-glycans and proline-rich peptides. We previously reported the under-O-glycosylation of the hinge in serum IgA1 and deposited IgA1 in glomeruli (glomerular IgA1) in IgA nephropathy. The clinical development and exacerbation of IgA nephropathy frequently are preceded by episodes of upper respiratory tract infections. Therefore, tonsils, which represent the predominant immunocompetent tissue of the upper respiratory tract, may be related to the pathogenesis of IgA nephropathy. In this study, we investigated the O-glycan structure of IgA1 produced by tonsillar lymphocytes (tonsillar IgA1), suspecting that tonsillar IgA1 is one of the origins of glomerular IgA1 in patients with IgA nephropathy. Methods: Extracted tonsils were obtained from 7 patients with IgA nephropathy and 5 patients with chronic tonsillitis as controls. Tonsillar lymphocytes separated from extracted tonsils were cultured for 7 days, and IgA1 in the culture medium was purified. The varieties of O-glycans in tonsillar IgA1 were determined from the molecular weights measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: A significant increase in the percentage of asialo-agalacto type O-glycans was found in tonsillar IgA1 in 4 of 7 patients with IgA nephropathy (57.1%) compared with controls. Between the IgA nephropathy and control groups, the difference was statistically significant (P = 0.047). Conclusion: This study provides precise information about the structure of O-glycans in tonsillar IgA1 in patients with IgA nephropathy. Our results suggest that tonsils produced the underglycosylated IgA1 molecules in patients with IgA nephropathy.