An acute model for IgA-mediated glomerular inflammation in rats induced by monoclonal polymeric rat IgA antibodies

Stad, Robert; Bruijn, Jan A.; Gijlswijk‐Janssen, Daniëlle J. van; Es, Leendert A. van; Daha, Mohamed R.

doi:10.1111/j.1365-2249.1993.tb03430.x

Cited by 33 publications

(10 citation statements)

References 31 publications

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“…Mesangial cells in the S-shaped body and immature glomeruli in the fetuses on GDs 18 and 21, as well as in the neonates on day 1, reacted strongly to α-SMA, and the reactivity gradually reduced until adulthood. In glomerular injury, such as IgA and anti-Thy-1 antibody nephropathy, mesangial cells have been considered to undergo transdifferentiation into myofibroblasts (expressing α-SMA), culminating in glomerulosclerosis 20 , 25 . Because the Thy-1-reacting mesangial cells during early nephrogenesis also expressed α-SMA, transdifferentiation in glomerulosclerosis implies that glomerular mesangial cells undergo regression, thus showing the nature of immature mesangial cells.…”

Section: Discussionmentioning

confidence: 99%

Thy-1 Expressing Mesenchymal Cells in Rat Nephrogenesis in Correlation with Cells Immunoreactive for .ALPHA.-Smooth Muscle Actin and Vimentin

et al. 2010

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Thy-1 expression may influence myofibroblast development. Through the epithelial-mesenchymal transition (EMT), injured renal epithelial cells undergo regression to the metanephric mesenchymal phenotype and then acquire a myofibroblastic nature (expressing α-smooth muscle actin; α-SMA). Because the metanephric blastema differentiates into mesenchymal and renal epithelial cells, we investigated Thy-1 immunoexpression during nephrogenesis in F344 rats in correlation with vimentin and α-SMA expressions. Kidney samples were obtained from fetuses on gestation days 18 and 21, neonates on days 1-18 and adults at 6 weeks of age. Mesangial cells in S-shaped bodies and immature and mature glomeruli continuously expressed both Thy-1 and α-SMA during early nephrogenesis (fetuses and neonates on days 1-9). During early nephrogenesis, loosely-arranged blastemal cell-derived mesenchymal cells in the cortex and medulla also exhibited Thy-1 and α-SMA, although the α-SMA expression was weaker than that of Thy-1. Vimentin expression coincided with that of Thy-1. These findings indicate that the derivation of α-SMA-expressing myofibroblastic cells may be related to mesangial or blastemal cells expressing both Thy-1 and α-SMA. Interestingly, there was a difference in Thy-1 expression between cortical and medullary tubulointerstitial cells from late nephrogenesis (neonates on days 12-18) and those from adults in that the cortical cells reacted faintly or negatively to Thy-1, whereas the medullary cells reacted strongly to Thy-1; additionally, bundle-arranged mesenchymal cells that were only observed in the neonates on days 1-12 reacted strongly to α-SMA, but faintly to Thy-1. Blastemal cell-derived mesenchymal cells seem to alter the immunoexpressions of Thy-1 and α-SMA, depending on the conditions which they develop. Thy-1 immunoexpression would be useful for investigation of reverse embryogenesis, which might occur in fibrotic kidneys.

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Section: Discussionmentioning

confidence: 99%

Thy-1 Expressing Mesenchymal Cells in Rat Nephrogenesis in Correlation with Cells Immunoreactive for .ALPHA.-Smooth Muscle Actin and Vimentin

et al. 2010

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“… 11 Furthermore, a rat model of IgA-mediated glomerular inflammation demonstrated that polymeric but not monomeric IgA triggered mesangial C3 deposition and not C4 or C1q deposition. 12 …”

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confidence: 99%

Circulating complement factor H–related proteins 1 and 5 correlate with disease activity in IgA nephropathy

Medjeral-Thomas

Lomax-Browne

Beckwith

et al. 2017

Kidney International

110

123

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IgA nephropathy (IgAN) is a common cause of chronic kidney disease and end-stage renal failure, especially in young people. Due to a wide range of clinical outcomes and difficulty in predicting response to immunosuppression, we need to understand why and identify which patients with IgAN will develop progressive renal impairment. A deletion polymorphism affecting the genes encoding the complement factor H-related protein (FHR)-1 and FHR-3 is robustly associated with protection against IgAN. Some FHR proteins, including FHR-1 and FHR-5, antagonize the ability of complement factor H (fH), the major negative regulator of the complement alternative pathway, to inhibit complement activation on surfaces, a process termed fH deregulation. From a large cohort of patients, we demonstrated that plasma FHR-1 and the FHR-1/fH ratio were elevated in IgAN and associated with progressive disease. Plasma FHR-1 negatively correlated with eGFR but remained elevated in patients with IgAN with normal eGFR. Serum FHR5 was slightly elevated in IgAN but did not correlate with eGFR. Neither FHR5 levels nor the FHR-5/fH ratio was associated with progressive disease. However, higher serum FHR-5 levels were associated with a lack of response to immunosuppression, the presence of endocapillary hypercellularity, and histology scores of disease severity (the Oxford Classification MEST score). Thus, FHR-1 and FHR-5 have a role in IgAN disease progression.

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“…In the model of IgAN instigated by injection of haptenated F(ab')2 anti-Thy1 antibody followed by rat IgA specific for the hapten, proteinuria and glomerular C3 deposition were correlated and developed after only injection of polymeric (as opposed to monomeric) IgA antibody, as did glomerular influx of monocytes [109]. Upon deposition of pIgA in the mesangium, rats pretreated with cobra venom factor did not develop the proteinuria, glomerular deposits of C3 or C9 or glomerular macrophage influx observed in normal rats, despite an identical pattern of glomerular IgA [131].…”

Section: Co-deposits Of Other Ig Classes and Complementmentioning

confidence: 97%

“…Like the binding to concanavalin A, binding of IgA to gliadin occurs on the basis of lectin properties; the gliadin then serves as a bridge to trigger deposition of both specific and nonspecific IgA into glomeruli [108]. Modifications of the anti-Thy 1.1 model of glomerulonephritis have exploited the affinity of antigen or antibody within glomerular deposits to promote IgA deposits in rats [109][110][111][112]. Again, these models demonstrate the plasticity of established glomerular deposits subject to the influence of circulating macromolecules, similar to the previous observations with IgG immune deposits [93][94][95].…”

Section: Affinity For Glomerular Componentsmentioning

confidence: 99%

Prospects and Perspectives on IgA Nephropathy from Animal Models

Emancipator

2011

Contributions to Nephrology

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The focus of this chapter is a systematic and critical review of the insights that experimental models have contributed to our understanding of IgA nephropathy (IgAN). We consider the generation of IgA subject to glomerular deposition, the partitioning of IgA between the circulation and glomeruli, the clearance of IgA and complexes containing IgA from the circulation, the 'upstream' effectors of glomerular pathophysiology, the inflammatory mediators that connect intraglomerular stimuli to functional and morphologic effects, and the contribution of animal models to our current understanding of the role that glycosylation of IgA plays in the genesis of IgAN. In each of these subsections, the evidence in favor of each principle or hypothesis is weighed in consideration of other potentially contradictory evidence and relevant issues related to IgAN in patients. The key limitations of each model system are presented, and where possible, reconciliation of discrepant observations are proposed. Subsequently, a synopsis of spontaneous models that do not offer particular mechanistic insights, and a compilation of experimental therapeutic initiatives, are reviewed. In all respects, the discussion of observations in patients or cells in vitro is limited to points where these data impinge upon interpretation of the data derived from the animal models.

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An acute model for IgA-mediated glomerular inflammation in rats induced by monoclonal polymeric rat IgA antibodies

Cited by 33 publications

References 31 publications

Thy-1 Expressing Mesenchymal Cells in Rat Nephrogenesis in Correlation with Cells Immunoreactive for .ALPHA.-Smooth Muscle Actin and Vimentin

Thy-1 Expressing Mesenchymal Cells in Rat Nephrogenesis in Correlation with Cells Immunoreactive for .ALPHA.-Smooth Muscle Actin and Vimentin

Circulating complement factor H–related proteins 1 and 5 correlate with disease activity in IgA nephropathy

Prospects and Perspectives on IgA Nephropathy from Animal Models

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