Glomerular FcαR expression and disease activity in IgA nephropathy

Abstract

In this study, we examined the receptors for the Fc portion of immunoglobulin A (IgA) (FcαR) in the glomeruli as well as circulating polymorphonuclear leukocytes and monocytes at the mRNA level by reverse transcription—polymerase chain reaction (RT-PCR) assay and at the protein level by an immunohistochemistry/flow cytometry technique using a specific anti-FcαR monoclonal antibody (My 43). Glomeruli were isolated from biopsy specimens of renal tissues from IgA nephropathy (IgAn; 20 cases) and non-IgA mesangial proliferative glomerulonephritis (PGN; 13 cases) patients, and from normal renal tissue specimens obtained from kidneys removed because of malignancies (five cases) applying the microdissection method. There was a relative increase in FcαR in the circulating phagocytes from IgAN patients compared with those PGN and healthy controls. FcαR expression was present in approximately 40% of glomeruli samples from IgAN patients at the message levels. FcαR-positive specimens were also strongly positive for expression of tumor necrosis factor-α, interleukin-1, and interleukin-6 mRNA. Specimens from PGN patients and healthy controls did not show any detectable FcαR message. Serum IgA levels and severity of hematuria were significantly higher in patients with positive FcαR expression. A message for FcαR was detected in the tissues that were more damaged histologically. Our data suggest that there is some in vivo induction of glomerular FcαR expression, possibly mediated by a synergistic stimulus from IgA and inflammatory cytokines, and the expressed receptor is likely to be involved in the disease process of IgAN.