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Pediatric Nephrology

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14.02.2017 | Editorial

C4d deposits in IgA nephropathy: where does complement activation come from?

verfasst von: Rosanna Coppo

Erschienen in: Pediatric Nephrology | Ausgabe 7/2017

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Excerpt

Among the conundrums surrounding immunoglobulin A nephropathy (IgAN) are its variable course and which biomarkers are best for predicting outcomes and need for treatment in potentially progressive patients [1]. The pathogenesis of IgAN is thought to be due to several factors (“hits”) [2] which play a permissive role in the development of IgA deposits that have an inflammatory potential, leading to glomerular damage. The production of galactose-deficient IgA1 (Gd-IgA1) as a result of defective galactosylation of O-linked glycans typical of the IgA1 molecule is increased in patients with IgAN, but also in healthy relatives, suggesting the need of additional hits. Gd-IgA1 binds to soluble CD89 (Fc alphaRI, myeloid IgA Fc receptor) and forms IgA1-CD89 complexes which interact with transferrin receptors (CD71/TfR1) and transglutaminase 2 (TGase2) in mesangial cells, thereby activating mediators and matrix production [3]. Moreover, Gd-IgA1 induces antiglycan autoantibody synthesis, leading to macromolecular Gd-IgA1(CD89)/IgG or IgA anti-Gd-IgA1 immune complex formation and renal deposition [2]. However, renal damage and progression towards sclerosis is highly variable, hence the presence of a crucial additional hit is envisaged. Complement activation is an attractive candidate for the pivotal hit in IgAN as the cue for triggering the inflammation and progression that is responsible for the variable clinical outcome. …

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Titel: C4d deposits in IgA nephropathy: where does complement activation come from?
verfasst von: Rosanna Coppo
Publikationsdatum: 14.02.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Nephrology / Ausgabe 7/2017
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-016-3575-2

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C4d deposits in IgA nephropathy: where does complement activation come from?

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