Integrin expression and IgA nephropathy: In vitro modulation by IgA with altered glycosylation and macromolecular IgA

Background. Signal transduction by mesangial cell (MC) integrins regulates cell growth and survival, extracellular matrix production, and organization . The aim of the study was to investigate human MC integrin modulation by d ifferently glycosylated IgA and macromolecular IgA, which are thought to pl ay a pathogenetic role in IgA nephropathy (IgAN). Methods. MCs were incubated with purified human polymeric IgA, heat-aggrega ted IgA, IgA glycoforms generated by enzymatic hydrolysis of saccharide res idues and serum fractions from IgAN patients, and controls isolated by lect in affinity and containing IgA with peculiar glycan patterns. Integrins wer e quantitated by flow cytometry. Results. Cultured MCs highly expressed alpha (v)beta (3) and some alpha (3) beta (1); alpha (v)beta (3) was up-regulated by matrix components (P < 0.02 ). In vitro desialylated and degalactosylated polymeric human IgA enhanced <alpha>(v)beta (3) expression on cultured MCs (P < 0.001). Serum IgA glycof orms isolated from IgAN patients with high exposure of internal sugars, Gal NAc, Neu5Ac2,6GalNAc, and Man enhanced a, expression on cultured MCs more t han healthy controls. Conclusions. These data support the hypothesis that IgA glycation plays a r ole in modulating the cell-matrix interaction, and that this mechanism can be operating in IgAN.