AUTOIMMUNITY IN IgA NEPHROPATHY

Ballardie, F W; Williams, Shelley; Brenchley, P; O'Donoghue, D J

doi:10.1016/s0140-6736(88)90637-x

Cited by 45 publications

(17 citation statements)

References 17 publications

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“…In contrast to a preliminary communication reporting increased monocyte IL-6 release during macroscopic haematuria (Ballardie et al, 1990), we failed to demonstrate increased IL-6 production from PBMC that consisted of monocytes, T and B cells and monocytes only comprised <4% of PBMC. The IL-6-dependent regulatory defect suggested by Ballardie et al (1990) could be related to the disease activity, since monocyte IL-6 release was raised only during synpharyngitic macroscopic haematuria and IL-6-mediated acute-phase protein responses during infection (Le & Vilcek, 1989). T cells stimulated with antigen (Kelso et al, 1982) or IL-2 (Vilcek et al, 1985) secrete IFN-y, and some studies have suggested that IFN-y acts in an autocrine manner (Simon et al, 1987).…”

Section: Discussioncontrasting

confidence: 99%

“…It is speculated that increased IL-4R expression in IgA nephropathy could be related to increased IL-2R expression, as suggested by murine and human experiments that the IL-2R and IL-4R may co-modulate each other's expression (Spits et al, 1987;. In contrast to a preliminary communication reporting increased monocyte IL-6 release during macroscopic haematuria (Ballardie et al, 1990), we failed to demonstrate increased IL-6 production from PBMC that consisted of monocytes, T and B cells and monocytes only comprised <4% of PBMC. The IL-6-dependent regulatory defect suggested by Ballardie et al (1990) could be related to the disease activity, since monocyte IL-6 release was raised only during synpharyngitic macroscopic haematuria and IL-6-mediated acute-phase protein responses during infection (Le & Vilcek, 1989).…”

Section: Discussionmentioning

confidence: 98%

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Cytokine production by peripheral blood mononuclear cells in IgA nephropathy

Lai

Leung

et al. 1991

Clinical and Experimental Immunology

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SUMMARY The regulation of cytokine production and T cell proliferation by other cytokines is mandatory in mediating inflammatory responses but the full understanding is far from complete. We have previously reported increased production of IL‐2 and IL‐2 receptors (IL‐2R) in IgA nephropathy. The present study was undertaken to examine other cytokine production during T cell activation in IgA nephropathy. Peripheral blood mononuclear cells (PBMC) from 17 IgA nephritic patients and 14 controls were cultured with phytohaemagglutinin and phorbol myristate acetate for 48 h for maximal cytokine production. IL‐2Rs and IL‐4 receptors (IL‐4Rs) expressed on cultured PBMC were studied by a radioimmunoassay using monoclonal antibodies against these receptors. Although the total cellular IL‐2R expression and percentages of T helper and T suppressor cells did not differ between the patients and controls, there was a significant increase in activated T helper cells expressing IL‐2R in patients with IgA nephropathy. The total cellular IL‐4R expression was elevated in IgA nephritic patients (P<0.005). IL‐2 production by PBMC was raised in IgA nephritic patients compared with controls (P<0.05) but no difference in IL‐4 or IL‐6 production was observed. The interferon‐gamma production by PBMC was significantly increased in patients with IgA nephropathy (P< 0.025). No correlation was observed between individual cytokine levels. Our data suggest there are selective increases in cytokine production in IgA nephropathy.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Cytokine production by peripheral blood mononuclear cells in IgA nephropathy

Lai

Leung

et al. 1991

Clinical and Experimental Immunology

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“…However, the absence of positive results using control sera strongly argues against such a mechanism. Localization of FITC-conjugated serum IgG, binding to the capillary loops and periphery of the mesangial stalk, confirms previous results (33), and this site, the glomerular region preferentially associated with IgG deposits in renal biopsy studies (26), suggests that the mesangial antigen may be concentrated, or exposed, at these sites in normal renal tissue. The IgG from ELISA-positive serum also bound to a proportion ofmesangial cells in culture in a uniform speckled membrane-associated pattern implying that the target antigen is a membrane component or closely associated with the membrane.…”

Section: Localization Of Antigen Immunofluorescence Studiessupporting

confidence: 88%

“…Preparation of whole glomerular antigen. Whole glomeruli from more than one source ofhuman tissue were separated and disrupted by prolonged sonication at 4°C and ultracentrifuged, and the supernatant was dialyzed against PBS and antibody binding detected by the standard form of previously described ELISA (33). F(ab')2 studies.…”

Section: Laboratory Methodsmentioning

confidence: 99%

Mesangial cell autoantigens in immunoglobulin A nephropathy and Henoch-Schönlein purpura.

O'Donoghue¹,

Darvill²,

Ballardie³

1991

J. Clin. Invest.

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“…Therefore, these approaches did not convincingly identify a uniformly encountered exogenous antigen as a component of the mesangial deposits and/or CIC. Endogenous glomerular antigens such as basement membrane collagens have been considered as components of in situ-formed IC in IgAN [16] . However, other reports questioned their participation [17] .…”

Section: Characterization Of Iga1 Mesangial Deposits and Circulating mentioning

confidence: 99%

Role of Aberrant Glycosylation of IgA1 Molecules in the Pathogenesis of IgA Nephropathy

Městecký

Tomana²,

Moldoveanu³

et al. 2008

Kidney Blood Press Res

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Studies of the properties of immune complexes (IC) in the circulation, urine, and mesangium of IgA nephropathy (IgAN) patients have provided data relevant to the pathogenesis of this disease. IC contain predominantly polymeric IgA1 molecules which are deficient in galactose (Gal) residues on O-linked glycan chains in the hinge region (HR) of their heavy (H) chains. As a result of this aberrancy, a novel antigenic determinant(s) involving N-acetylgalactosamine (GalNAc) and perhaps sialic acid (SA) of O-linked glycans is generated and recognized by naturally occurring GalNAc-specific antibodies. Thus, IC in IgAN consist of Gal-deficient IgA1 molecules as an antigen, and GalNAc-specific IgG and/or IgA1 as an antibody. IgG antibodies to Gal-deficient IgA1 are probably induced by cross-reactive microbial antigens; they are present at variable levels not only in humans with or without IgAN but also in many phylogenetically diverse vertebrate species. Incubation of human mesangial cells with IC from sera of IgAN patients indicated that stimulation of cellular proliferative activity was restricted to the large (>800 kDa) complexes. These findings suggest that experimental approaches that prevent the formation of large Gal-deficient IgA1-IgG IC may be applied ultimately in an immunologically mediated therapy.

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AUTOIMMUNITY IN IgA NEPHROPATHY

Cited by 45 publications

References 17 publications

Cytokine production by peripheral blood mononuclear cells in IgA nephropathy

Cytokine production by peripheral blood mononuclear cells in IgA nephropathy

Mesangial cell autoantigens in immunoglobulin A nephropathy and Henoch-Schönlein purpura.

Role of Aberrant Glycosylation of IgA1 Molecules in the Pathogenesis of IgA Nephropathy

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