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JAK Inhibitors and Modulation of B Cell Immune Responses in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, systemic immune-mediated inflammatory disease that can lead to joint destruction, functional disability and substantial comorbidity due to the involvement of multiple organs and systems. B cells have several important roles in RA pathogenesis, namely through a...

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Autores principales: Moura, Rita A., Fonseca, João Eurico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892604/
https://www.ncbi.nlm.nih.gov/pubmed/33614673
http://dx.doi.org/10.3389/fmed.2020.607725
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author Moura, Rita A.
Fonseca, João Eurico
author_facet Moura, Rita A.
Fonseca, João Eurico
author_sort Moura, Rita A.
collection PubMed
description Rheumatoid arthritis (RA) is a chronic, systemic immune-mediated inflammatory disease that can lead to joint destruction, functional disability and substantial comorbidity due to the involvement of multiple organs and systems. B cells have several important roles in RA pathogenesis, namely through autoantibody production, antigen presentation, T cell activation, cytokine release and ectopic lymphoid neogenesis. The success of B cell depletion therapy with rituximab, a monoclonal antibody directed against CD20 expressed by B cells, has further supported B cell intervention in RA development. Despite the efficacy of synthetic and biologic disease modifying anti-rheumatic drugs (DMARDs) in the treatment of RA, few patients reach sustained remission and refractory disease is a concern that needs critical evaluation and close monitoring. Janus kinase (JAK) inhibitors or JAKi are a new class of oral medications recently approved for the treatment of RA. JAK inhibitors suppress the activity of one or more of the JAK family of tyrosine kinases, thus interfering with the JAK-Signal Transducer and Activator of Transcription (STAT) signaling pathway. To date, there are five JAK inhibitors (tofacitinib, baricitinib, upadacitinib, peficitinib and filgotinib) approved in the USA, Europe and/ or Japan for RA treatment. Evidence from the literature indicates that JAK inhibitors interfere with B cell functions. In this review, the main results obtained in clinical trials, pharmacokinetic, in vitro and in vivo studies concerning the effects of JAK inhibitors on B cell immune responses in RA are summarized.
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spelling pubmed-78926042021-02-20 JAK Inhibitors and Modulation of B Cell Immune Responses in Rheumatoid Arthritis Moura, Rita A. Fonseca, João Eurico Front Med (Lausanne) Medicine Rheumatoid arthritis (RA) is a chronic, systemic immune-mediated inflammatory disease that can lead to joint destruction, functional disability and substantial comorbidity due to the involvement of multiple organs and systems. B cells have several important roles in RA pathogenesis, namely through autoantibody production, antigen presentation, T cell activation, cytokine release and ectopic lymphoid neogenesis. The success of B cell depletion therapy with rituximab, a monoclonal antibody directed against CD20 expressed by B cells, has further supported B cell intervention in RA development. Despite the efficacy of synthetic and biologic disease modifying anti-rheumatic drugs (DMARDs) in the treatment of RA, few patients reach sustained remission and refractory disease is a concern that needs critical evaluation and close monitoring. Janus kinase (JAK) inhibitors or JAKi are a new class of oral medications recently approved for the treatment of RA. JAK inhibitors suppress the activity of one or more of the JAK family of tyrosine kinases, thus interfering with the JAK-Signal Transducer and Activator of Transcription (STAT) signaling pathway. To date, there are five JAK inhibitors (tofacitinib, baricitinib, upadacitinib, peficitinib and filgotinib) approved in the USA, Europe and/ or Japan for RA treatment. Evidence from the literature indicates that JAK inhibitors interfere with B cell functions. In this review, the main results obtained in clinical trials, pharmacokinetic, in vitro and in vivo studies concerning the effects of JAK inhibitors on B cell immune responses in RA are summarized. Frontiers Media S.A. 2021-02-05 /pmc/articles/PMC7892604/ /pubmed/33614673 http://dx.doi.org/10.3389/fmed.2020.607725 Text en Copyright © 2021 Moura and Fonseca. 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) and the copyright owner(s) 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 Medicine
Moura, Rita A.
Fonseca, João Eurico
JAK Inhibitors and Modulation of B Cell Immune Responses in Rheumatoid Arthritis
title JAK Inhibitors and Modulation of B Cell Immune Responses in Rheumatoid Arthritis
title_full JAK Inhibitors and Modulation of B Cell Immune Responses in Rheumatoid Arthritis
title_fullStr JAK Inhibitors and Modulation of B Cell Immune Responses in Rheumatoid Arthritis
title_full_unstemmed JAK Inhibitors and Modulation of B Cell Immune Responses in Rheumatoid Arthritis
title_short JAK Inhibitors and Modulation of B Cell Immune Responses in Rheumatoid Arthritis
title_sort jak inhibitors and modulation of b cell immune responses in rheumatoid arthritis
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892604/
https://www.ncbi.nlm.nih.gov/pubmed/33614673
http://dx.doi.org/10.3389/fmed.2020.607725
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