Identification of a novel Fcα 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 mesangial cell (MC). We have characterized a novel mesangial receptor that recognizes the Fc portion of IgA. Methods. Five primary MC cultures were evaluated for IgA binding by how cytometry, and specificity of binding was determined by competitive inhibition. Relative affinities of the receptor for all IgA isoforms were also determined, and binding of pIgA1 was compared to monomer. The identified Fc receptor was then compared with CD89, hitherto the only other Fc alpha receptor reported. CD89 protein and mRNA expression were detected by conventional and intracellular how cytometry, sequencing of reverse transcription-polymerase chain reaction (RT-PCR) products, and Northern blotting. Results. All MCs constitutively expressed a receptor that bound IgA in an Fc 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 binds pIgA with high affinity and may therefore mediate the mesangial injury that follows IgA deposition in IgAN. While immunogenically distinct, the mesangial Fc alpha receptor may share some molecular homology with CD89, as mRNA transcripts with partial identity to CD89 were found in all five MC cultures.