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The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy

Advances in our understanding of the pathogenesis of immunoglobulin A nephropathy (IgAN) have led to the identification of novel therapeutic targets and potential disease-specific treatments. Specifically, a proliferation-inducing ligand (APRIL) has been implicated in the pathogenesis of IgAN, media...

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Autores principales: Yeo, See Cheng, Barratt, Jonathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695512/
http://dx.doi.org/10.1093/ckj/sfad200
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author Yeo, See Cheng
Barratt, Jonathan
author_facet Yeo, See Cheng
Barratt, Jonathan
author_sort Yeo, See Cheng
collection PubMed
description Advances in our understanding of the pathogenesis of immunoglobulin A nephropathy (IgAN) have led to the identification of novel therapeutic targets and potential disease-specific treatments. Specifically, a proliferation-inducing ligand (APRIL) has been implicated in the pathogenesis of IgAN, mediating B-cell dysregulation and overproduction of pathogenic galactose-deficient IgA1 (Gd-IgA1). Animal and clinical studies support the involvement of APRIL in the pathogenesis and progression of IgAN. An elevated level of APRIL is found in IgAN when compared with controls, which correlates with the level of Gd-IgA1 and associates with more severe disease presentation and worse outcomes. Conversely, anti-APRIL therapy reduces pathogenic Gd-IgA1 and IgA immune complex formation and ameliorates the severity of kidney inflammation and injury. Genome-wide association studies in IgAN have identified TNFSF13 and TNFRSF13B, a cytokine ligand-receptor gene pair encoding APRIL and its receptor, respectively, as risk susceptibility loci in IgAN, further supporting the causal role of the APRIL signalling pathway in IgAN. Several novel experimental agents targeting APRIL, including atacicept, telitacicept, zigakibart and sibeprenlimab, are currently under investigation as potential therapies in IgAN. Preliminary results suggest that these agents are well-tolerated, and reduce levels of Gd-IgA1, with corresponding improvement in proteinuria. Further studies are ongoing to confirm the safety and efficacy of anti-APRIL approaches as an effective therapeutic strategy in IgAN.
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spelling pubmed-106955122023-12-05 The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy Yeo, See Cheng Barratt, Jonathan Clin Kidney J CKJ Review Advances in our understanding of the pathogenesis of immunoglobulin A nephropathy (IgAN) have led to the identification of novel therapeutic targets and potential disease-specific treatments. Specifically, a proliferation-inducing ligand (APRIL) has been implicated in the pathogenesis of IgAN, mediating B-cell dysregulation and overproduction of pathogenic galactose-deficient IgA1 (Gd-IgA1). Animal and clinical studies support the involvement of APRIL in the pathogenesis and progression of IgAN. An elevated level of APRIL is found in IgAN when compared with controls, which correlates with the level of Gd-IgA1 and associates with more severe disease presentation and worse outcomes. Conversely, anti-APRIL therapy reduces pathogenic Gd-IgA1 and IgA immune complex formation and ameliorates the severity of kidney inflammation and injury. Genome-wide association studies in IgAN have identified TNFSF13 and TNFRSF13B, a cytokine ligand-receptor gene pair encoding APRIL and its receptor, respectively, as risk susceptibility loci in IgAN, further supporting the causal role of the APRIL signalling pathway in IgAN. Several novel experimental agents targeting APRIL, including atacicept, telitacicept, zigakibart and sibeprenlimab, are currently under investigation as potential therapies in IgAN. Preliminary results suggest that these agents are well-tolerated, and reduce levels of Gd-IgA1, with corresponding improvement in proteinuria. Further studies are ongoing to confirm the safety and efficacy of anti-APRIL approaches as an effective therapeutic strategy in IgAN. Oxford University Press 2023-12-04 /pmc/articles/PMC10695512/ http://dx.doi.org/10.1093/ckj/sfad200 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the ERA. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle CKJ Review
Yeo, See Cheng
Barratt, Jonathan
The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy
title The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy
title_full The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy
title_fullStr The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy
title_full_unstemmed The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy
title_short The contribution of a proliferation-inducing ligand (APRIL) and other TNF superfamily members in pathogenesis and progression of IgA nephropathy
title_sort contribution of a proliferation-inducing ligand (april) and other tnf superfamily members in pathogenesis and progression of iga nephropathy
topic CKJ Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695512/
http://dx.doi.org/10.1093/ckj/sfad200
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