Glomerular FcαR expression and disease activity in IgA nephropathy

Kashem, Abul; Endoh, Masayuki; Yano, Naohiro; Yamauchi, Fumio; Nomoto, Yasuo; Sakai, Hideto; Kurokawa, Kiyoshi

doi:10.1016/s0272-6386(97)90284-5

Cited by 39 publications

(34 citation statements)

References 18 publications

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“…Using the same antibody against Fc␣R1 (A59) for direct immunofluorescence studies, we failed to confirm downregulation of Fc␣R1 on leukocytes in IgAN. Instead, we observed increased percentages of granulocytes and monocytes expressing Fc␣R1 among patients with IgAN, as reported by others (8,26). In both groups of subjects, we failed to establish a negative correlation between plasma IgA levels and the expression of Fc␣R1 on granulocytes or monocytes, as reported previously (9).…”

Section: Discussionsupporting

confidence: 81%

“…In comparisons of fluorescence intensity, the levels of endogenous -IgA and -IgA bound to the surface of either granulocytes or monocytes from patients with IgAN were higher than values for healthy control subjects. Interestingly, conflicting observations on Fc␣R1 reactivity on blood cells from patients with IgAN were recorded (8,9,26). Grossetete et al (9) attributed the contradicting findings from their laboratory to crosslinking by a secondary antibody in indirect immunofluorescence studies.…”

Section: Discussionmentioning

confidence: 99%

“…It is also thought that the expression of IgA receptors on and the binding of IgA to circulating leukocytes might affect the mesangial uptake of IgA in IgAN. However, studies of IgA receptors on blood cells from patients with IgAN are few and the results are inconclusive (8,9). The tested hypothesis was that polymeric -IgA from patients with IgAN would demonstrate increased binding to leukocytes that might become activated or "primed" (10).…”

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confidence: 99%

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Characteristics of Polymeric λ-IgA Binding to Leukocytes in IgA Nephropathy

Lai¹,

Chan²,

Tang³

et al. 2002

Journal of the American Society of Nephrology

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Abstract. IgA nephropathy (IgAN) is characterized by predominant mesangial polymeric IgA1 (pIgA1) deposits, with increased plasma IgA1 levels. Plasma IgA levels are determined by the rate of IgA production, uptake by leukocytes, and removal by hepatocytes. Fc␣ receptor 1 (Fc␣R1) is a candidate molecule for the regulation of IgA levels, but reports of its expression in leukocytes in IgAN are conflicting.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Characteristics of Polymeric λ-IgA Binding to Leukocytes in IgA Nephropathy

Lai¹,

Chan²,

Tang³

et al. 2002

Journal of the American Society of Nephrology

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“…Thus, FcαR may be the functional candidate for a genetic study to identify susceptibility to IgAN. Polymorphism in the regulatory region for FcαR gene expression is thought to be especially important, because earlier studies reported increased expression of FcαR in patients with IgAN (Kashem et al 1994;Monteiro et al 1995;Kashem et al 1997).…”

Section: Resultsmentioning

confidence: 99%

Genetic polymorphisms in the promoter and 5′ UTR region of the Fc α receptor (CD89) are not associated with a risk of IgA nephropathy

et al. 2001

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The molecular mechanisms of immunoglobulin A glomerulonephritis (IgAN), the most prevalent form of primary glomerulonephritis, remain poorly understood. Recently, the essential role of soluble Fc α receptor (FcαR) in the formation of the pathogenic immune complex has been revealed. We screened genomic DNA samples from patients with IgAN and those with other glomerular diseases for polymorphisms in the promoter and the 5Ј-untranslated region region of the FcαR gene by direct nucleotide sequencing. We found three common polymorphisms in this region, T-114C, T-27C, and Tϩ56C from the putative transcription initiation site. Each genotype was determined in 151 patients with IgAN and 163 patients with other glomerular diseases shown to have no mesangial IgA deposition by renal biopsy. The haplotype analysis revealed tight linkage disequilibrium among them. An association study for the genotype, allele, and haplotype frequencies of the polymorphisms between the patients with histologically proven IgAN and those with other glomerular diseases showed no significant difference in the genotype, allele, and haplotype distributions between the two groups. The present study indicates that the analyzed polymorphisms of the FcαR gene do not appear to be primarily involved in the susceptibility to IgAN.

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“…The involvement of transmembrane FcaRI signaling by IgA-IC in the pathogenesis of GN remains unclear. Indirect evidence for a role of FcaRI in glomerular damage in IgAN comes from the detection of FcaRI mRNA in patients' glomeruli and damaged tissues [22]. This contrasts with the decreased surface expression of FcaRI on blood monocytes and neutrophils, due to shedding of receptors in soluble forms [16,23].…”

Section: Introductionmentioning

confidence: 99%

Fcα receptor I activation induces leukocyte recruitment and promotes aggravation of glomerulonephritis through the FcRγ adaptor

et al. 2007

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Myeloid cells bear Fc receptors (FcR) that mediate inflammatory signaling through the ITAM-containing FcRc adaptor. They express FcRc-associated FcaRI, which modulate either activating or inhibitory signaling depending on the type of ligand interaction. The role of FcaRIc in disease progression remains unknown, notably in IgA nephropathy (IgAN), one of major causes of end-stage renal disease, in which large amounts of circulating IgA-immune complexes (IC) may mediate receptor activation. To analyze the involvement of FcaRI activation in glomerulonephritis (GN), we generated Tg mice expressing a mutated, signaling-incompetent, human FcaRI R209L that cannot associate with FcRc. Like FcaRI wt -Tg mice, they developed mesangial IgA deposits but not macrophage infiltration. FcaRI activation in FcaRI wt , but not in FcaRI R209L , Tg mice resulted in marked inflammation with severe proteinuria and leukocyte infiltration in spontaneous IgAN or anti-glomerular basement membrane Ab-induced GN models. Receptor triggering of syngenically transferred FcaRI wt Tg macrophages into non-Tg animals induced their recruitment into injured kidneys during GN development. FcaRI wt cross-linking on macrophages activated MAP kinases and production of TNF-a and MCP-1. Moreover, IgA-IC from IgAN patients activated FcaRI and induced TNF-a production. Thus, FcaRI activation mediates GN progression by initiating a cytokine/ chemokine cascade that promotes leukocyte recruitment and kidney damage.

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Glomerular FcαR expression and disease activity in IgA nephropathy

Cited by 39 publications

References 18 publications

Characteristics of Polymeric λ-IgA Binding to Leukocytes in IgA Nephropathy

Characteristics of Polymeric λ-IgA Binding to Leukocytes in IgA Nephropathy

Genetic polymorphisms in the promoter and 5′ UTR region of the Fc α receptor (CD89) are not associated with a risk of IgA nephropathy

Fcα receptor I activation induces leukocyte recruitment and promotes aggravation of glomerulonephritis through the FcRγ adaptor

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