Glomerular Fc alphaR expression and disease activity in IgA nephropathy.
In this study, we examined the receptors for the Fc portion of immunoglobulin A (IgA) (Fc alphaR) 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-Fc alphaR 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 Fc alphaR in the circulating phagocytes from IgAN patients compared with those from PGN and healthy controls. Fc alphaR expression was present in approximately 40% of glomeruli samples from IgAN patients at the message levels. Fc alphaR-positive specimens were also strongly positive for expression of tumor necrosis factor-alpha, interleukin-1, and interleukin-6 mRNA. Specimens from PGN patients and healthy controls did not show any detectable Fc alphaR message. Serum IgA levels and severity of hematuria were significantly higher in patients with positive Fc alphaR expression. A message for Fc alphaR was detected in the tissues that were more damaged histologically. Our data suggest that there is some in vivo induction of glomerular Fc alphaR 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.
Kashem
A
A
Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan.
Endoh
M
M
Yano
N
N
Yamauchi
F
F
Nomoto
Y
Y
Sakai
H
H
Kurokawa
K
K
D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis*; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D007678:Kidney Glomerulus / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011961:Receptors, Fc / Q000032:analysis* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha