Expression and physical association of Fca receptor and Fc receptor c chain in human mesangial cells

Key words: FcaR; FcR c chain; IgA nephropathy; mesangial cells; physical association Background. Most intensive investigations on the pathogenesis of IgA nephropathy have focused on the process before IgA deposition and the characteristics of IgA/IgA immune complex (IgA IC), but it still Introduction remains uncertain whether mesangial IgA ICs may cause glomerular injuries directly or are only secondary IgA nephropathy is found widely and is recognized as events of another pathological process. To assess the the most common form of primary glomerular disease role of IgA ICs in IgA nephropathy, we investigated throughout the world. In long-term follow-up studies the characteristics of Fca receptor (FcaR) and FcR c of patients with IgA nephropathy, 25–40% of them chain which is a signalling subunit of FcR in human progressed to renal failure within 20 years or more mesangial cells (MCs). after initial discovery of the disease [1]. An understand-Methods. Gene expression of FcaR and FcR c chain ing of the sequential events in the pathogenesis of IgA of human cultured MCs was examined by RT–PCR nephropathy, which is a key issue for development of and subsequent Southern blot analyses. Sequence ana-successful therapy, is therefore essential. IgA nephro-lyses after subcloning were also performed for further pathy is characterized by predominant mesangial confirmation. Expression of FcaR and FcR c chain at depositions of IgA/IgA immune complex (IgA IC) and the protein level and their physical association in MCs elevation of the serum IgA ICs [2–4], and their contri-were determined by immunoprecipitation after stimula-bution to pathogenesis has been suggested. Intensive tion of the cells with heat-aggregated IgA. investigations by several groups revealed the character-Results. Two distinct cDNA products were amplified istics of glomerular or serum IgA in IgA nephropathy. from each cultured MC line. The sequence of the major It was confirmed that the glomerular IgA in patients product of ~900 bp was completely identical to that with IgA nephropathy was predominantly anionic of FcaR previously described. The smaller product had polymeric IgA1 [5–7]. Furthermore, it was shown that a 288 bp deletion which corresponded to exon 2 IgA in patients with IgA nephropathy had structural encoding the extracellular domain 2 of FcaR. Gene abnormalities [8]. expression of FcR c chain was also confirmed. Most of these studies focused on the process before Furthermore, we proved the physical association of IgA deposition (such as genetic and immunological FcaR with the FcR c chain by co-immunoprecipitation …