Identification of a novel Fc alpha receptor expressed by human mesangial cells

Background IgA nephropathy (IgAN) is characterized by mesangial deposits of polymeric IgA (pIgA). The pathological consequences of IgA deposition are believed to center on direct interaction between IgA and the glomerular mes angial cell (MC). We have characterized a novel mesangial receptor that rec ognizes the Fc portion of IgA. Methods. Five primary MC cultures were evaluated for IgA binding by how cyt ometry, and specificity of binding was determined by competitive inhibition . Relative affinities of the receptor for all IgA isoforms were also determ ined, and binding of pIgA1 was compared to monomer. The identified Fc recep tor was then compared with CD89, hitherto the only other Fc alpha receptor reported. CD89 protein and mRNA expression were detected by conventional an d intracellular how cytometry, sequencing of reverse transcription-polymera se chain reaction (RT-PCR) products, and Northern blotting. Results. All MCs constitutively expressed a receptor that bound IgA in an F c alpha-dependent fashion. The receptor recognized secretory and serum IgA1 and IgA2 equally, but pIgA bound with much greater affinity than monomer. At no time were we able to detect CD89 synthesis, although three novel CD89 -related mRNA transcripts were identified by RT-PCR. Conclusions. We have clearly demonstrated that MCs consistently express an Fc alpha R distinct from the myeloid Fc alpha R CD89. This novel receptor b inds pIgA with high affinity and may therefore mediate the mesangial injury that follows IgA deposition in IgAN. While immunogenically distinct, the m esangial Fc alpha receptor may share some molecular homology with CD89, as mRNA transcripts with partial identity to CD89 were found in all five MC cu ltures.