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Interferon targeted therapies in systemic lupus erythematosus

Type I interferons secreted by plasmacytoid dendritic cells (pDCs) play a crucial role in the pathogenesis of systemic lupus erythematosus by driving the formation of autoantibodies against nuclear debris. Inherited mutations causing activation of the Type I interferon pathway result in a phenotype...

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Detalles Bibliográficos
Autores principales: Misra, Durga Prasanna, Negi, Vir Singh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Mediterranean Journal of Rheumatology (MJR) 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045923/
https://www.ncbi.nlm.nih.gov/pubmed/32185249
http://dx.doi.org/10.31138/mjr.28.1.13
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author Misra, Durga Prasanna
Negi, Vir Singh
author_facet Misra, Durga Prasanna
Negi, Vir Singh
author_sort Misra, Durga Prasanna
collection PubMed
description Type I interferons secreted by plasmacytoid dendritic cells (pDCs) play a crucial role in the pathogenesis of systemic lupus erythematosus by driving the formation of autoantibodies against nuclear debris. Inherited mutations causing activation of the Type I interferon pathway result in a phenotype of systemic autoimmunity which resembles some of the manifestations of lupus. Patients with lupus have increased expression of interferon-stimulated genes in the peripheral blood mononuclear cells which is abrogated following immunosuppressive treatment. Recent therapeutic approaches have involved monoclonal antibodies directly targeting interferon alpha (sifalimumab, rontalizumab) or the use of interferon alpha kinoid to stimulate endogenous production of anti-interferon antibodies in lupus. Other drugs used in lupus such as hydroxychloroquine and bortezomib also reduce circulating levels of type I interferons. Newer therapeutic strategies being investigated in preclinical models of lupus that reduce the production of Type I interferons include dihydroartemisinin, Bruton’s tyrosine kinase antagonists, Bcl-2 antagonists and sphingosine-1 phosphate agonists.
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spelling pubmed-70459232020-03-17 Interferon targeted therapies in systemic lupus erythematosus Misra, Durga Prasanna Negi, Vir Singh Mediterr J Rheumatol Review Type I interferons secreted by plasmacytoid dendritic cells (pDCs) play a crucial role in the pathogenesis of systemic lupus erythematosus by driving the formation of autoantibodies against nuclear debris. Inherited mutations causing activation of the Type I interferon pathway result in a phenotype of systemic autoimmunity which resembles some of the manifestations of lupus. Patients with lupus have increased expression of interferon-stimulated genes in the peripheral blood mononuclear cells which is abrogated following immunosuppressive treatment. Recent therapeutic approaches have involved monoclonal antibodies directly targeting interferon alpha (sifalimumab, rontalizumab) or the use of interferon alpha kinoid to stimulate endogenous production of anti-interferon antibodies in lupus. Other drugs used in lupus such as hydroxychloroquine and bortezomib also reduce circulating levels of type I interferons. Newer therapeutic strategies being investigated in preclinical models of lupus that reduce the production of Type I interferons include dihydroartemisinin, Bruton’s tyrosine kinase antagonists, Bcl-2 antagonists and sphingosine-1 phosphate agonists. The Mediterranean Journal of Rheumatology (MJR) 2017-03-28 /pmc/articles/PMC7045923/ /pubmed/32185249 http://dx.doi.org/10.31138/mjr.28.1.13 Text en © 2017 The Mediterranean Journal of Rheumatology (MJR) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
spellingShingle Review
Misra, Durga Prasanna
Negi, Vir Singh
Interferon targeted therapies in systemic lupus erythematosus
title Interferon targeted therapies in systemic lupus erythematosus
title_full Interferon targeted therapies in systemic lupus erythematosus
title_fullStr Interferon targeted therapies in systemic lupus erythematosus
title_full_unstemmed Interferon targeted therapies in systemic lupus erythematosus
title_short Interferon targeted therapies in systemic lupus erythematosus
title_sort interferon targeted therapies in systemic lupus erythematosus
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045923/
https://www.ncbi.nlm.nih.gov/pubmed/32185249
http://dx.doi.org/10.31138/mjr.28.1.13
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