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Mechanisms of Kidney Injury in Lupus Nephritis – the Role of Anti-dsDNA Antibodies

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a breakdown of self-tolerance, production of auto-antibodies and immune-mediated injury, resulting in damage accrual in multiple organs. Kidney involvement, termed lupus nephritis, is a major cause of morbidity and mortalit...

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Autores principales: Yung, Susan, Chan, Tak Mao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569852/
https://www.ncbi.nlm.nih.gov/pubmed/26441980
http://dx.doi.org/10.3389/fimmu.2015.00475
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author Yung, Susan
Chan, Tak Mao
author_facet Yung, Susan
Chan, Tak Mao
author_sort Yung, Susan
collection PubMed
description Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a breakdown of self-tolerance, production of auto-antibodies and immune-mediated injury, resulting in damage accrual in multiple organs. Kidney involvement, termed lupus nephritis, is a major cause of morbidity and mortality that affects over half of the SLE population during the course of disease. The etiology of lupus nephritis is multifactorial and remains to be fully elucidated. Accumulating evidence suggests that in addition to forming immune complexes and triggering complement activation, anti-dsDNA antibodies contribute to the pathogenesis of lupus nephritis through binding, either directly or indirectly, to cross-reactive antigens or chromatin materials, respectively, to resident renal cells and/or extracellular matrix components, thereby triggering downstream cellular activation and proliferation as well as inflammatory and fibrotic processes. Several cross-reactive antigens that mediate anti-dsDNA antibody binding have been identified, such as annexin II and alpha-actinin. This review discusses the mechanisms through which anti-dsDNA antibodies contribute to immunopathogenesis in lupus nephritis. Corticosteroids combined with either mycophenolic acid (MPA) or cyclophosphamide is the current standard of care immunosuppressive therapy for severe lupus nephritis. This review also discusses recent data showing distinct effects of MPA and cyclophosphamide on inflammatory and fibrotic processes in resident renal cells.
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spelling pubmed-45698522015-10-05 Mechanisms of Kidney Injury in Lupus Nephritis – the Role of Anti-dsDNA Antibodies Yung, Susan Chan, Tak Mao Front Immunol Immunology Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a breakdown of self-tolerance, production of auto-antibodies and immune-mediated injury, resulting in damage accrual in multiple organs. Kidney involvement, termed lupus nephritis, is a major cause of morbidity and mortality that affects over half of the SLE population during the course of disease. The etiology of lupus nephritis is multifactorial and remains to be fully elucidated. Accumulating evidence suggests that in addition to forming immune complexes and triggering complement activation, anti-dsDNA antibodies contribute to the pathogenesis of lupus nephritis through binding, either directly or indirectly, to cross-reactive antigens or chromatin materials, respectively, to resident renal cells and/or extracellular matrix components, thereby triggering downstream cellular activation and proliferation as well as inflammatory and fibrotic processes. Several cross-reactive antigens that mediate anti-dsDNA antibody binding have been identified, such as annexin II and alpha-actinin. This review discusses the mechanisms through which anti-dsDNA antibodies contribute to immunopathogenesis in lupus nephritis. Corticosteroids combined with either mycophenolic acid (MPA) or cyclophosphamide is the current standard of care immunosuppressive therapy for severe lupus nephritis. This review also discusses recent data showing distinct effects of MPA and cyclophosphamide on inflammatory and fibrotic processes in resident renal cells. Frontiers Media S.A. 2015-09-15 /pmc/articles/PMC4569852/ /pubmed/26441980 http://dx.doi.org/10.3389/fimmu.2015.00475 Text en Copyright © 2015 Yung and Chan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Yung, Susan
Chan, Tak Mao
Mechanisms of Kidney Injury in Lupus Nephritis – the Role of Anti-dsDNA Antibodies
title Mechanisms of Kidney Injury in Lupus Nephritis – the Role of Anti-dsDNA Antibodies
title_full Mechanisms of Kidney Injury in Lupus Nephritis – the Role of Anti-dsDNA Antibodies
title_fullStr Mechanisms of Kidney Injury in Lupus Nephritis – the Role of Anti-dsDNA Antibodies
title_full_unstemmed Mechanisms of Kidney Injury in Lupus Nephritis – the Role of Anti-dsDNA Antibodies
title_short Mechanisms of Kidney Injury in Lupus Nephritis – the Role of Anti-dsDNA Antibodies
title_sort mechanisms of kidney injury in lupus nephritis – the role of anti-dsdna antibodies
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569852/
https://www.ncbi.nlm.nih.gov/pubmed/26441980
http://dx.doi.org/10.3389/fimmu.2015.00475
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