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The many faces of psoriatic arthritis: their genetic determinism

In this review, we propose a model of PsA as a complex genetically determined autoimmune-mediated disease having a heterogeneous variety of subphenotypes, with each subphenotype under the control of a different susceptibility-associated HLA allele. Since the specific HLA molecules encoded by each su...

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Detalles Bibliográficos
Autores principales: Winchester, Robert, FitzGerald, Oliver
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065456/
https://www.ncbi.nlm.nih.gov/pubmed/32159794
http://dx.doi.org/10.1093/rheumatology/kez325
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author Winchester, Robert
FitzGerald, Oliver
author_facet Winchester, Robert
FitzGerald, Oliver
author_sort Winchester, Robert
collection PubMed
description In this review, we propose a model of PsA as a complex genetically determined autoimmune-mediated disease having a heterogeneous variety of subphenotypes, with each subphenotype under the control of a different susceptibility-associated HLA allele. Since the specific HLA molecules encoded by each susceptibility allele dominantly select a T cell repertoire with the property of recognizing different peptides, we hypothesize each subphenotype reflects a distinct adaptive autoimmune response directed to different target molecules that is mediated by T cells within each selected repertoire. The interaction among the patients’ susceptibility alleles in the selection of their T cell repertoires determines a spectrum of overall clinical disease severity, varying from mild to severe. We further speculate that these different immune responses may result in activation of different immune effector pathways, which might therefore respond differently to various specific biologic agents.
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spelling pubmed-70654562020-03-13 The many faces of psoriatic arthritis: their genetic determinism Winchester, Robert FitzGerald, Oliver Rheumatology (Oxford) Reviews In this review, we propose a model of PsA as a complex genetically determined autoimmune-mediated disease having a heterogeneous variety of subphenotypes, with each subphenotype under the control of a different susceptibility-associated HLA allele. Since the specific HLA molecules encoded by each susceptibility allele dominantly select a T cell repertoire with the property of recognizing different peptides, we hypothesize each subphenotype reflects a distinct adaptive autoimmune response directed to different target molecules that is mediated by T cells within each selected repertoire. The interaction among the patients’ susceptibility alleles in the selection of their T cell repertoires determines a spectrum of overall clinical disease severity, varying from mild to severe. We further speculate that these different immune responses may result in activation of different immune effector pathways, which might therefore respond differently to various specific biologic agents. Oxford University Press 2020-03 2020-03-11 /pmc/articles/PMC7065456/ /pubmed/32159794 http://dx.doi.org/10.1093/rheumatology/kez325 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://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 Reviews
Winchester, Robert
FitzGerald, Oliver
The many faces of psoriatic arthritis: their genetic determinism
title The many faces of psoriatic arthritis: their genetic determinism
title_full The many faces of psoriatic arthritis: their genetic determinism
title_fullStr The many faces of psoriatic arthritis: their genetic determinism
title_full_unstemmed The many faces of psoriatic arthritis: their genetic determinism
title_short The many faces of psoriatic arthritis: their genetic determinism
title_sort many faces of psoriatic arthritis: their genetic determinism
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065456/
https://www.ncbi.nlm.nih.gov/pubmed/32159794
http://dx.doi.org/10.1093/rheumatology/kez325
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