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ACPA Status Correlates with Differential Immune Profile in Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a progressive erosive autoimmune disease that affects 1% of the world population. Anti-citrullinated protein autoantibodies (ACPA) are routinely used for the diagnosis of RA, however 20–30% of patients are ACPA negative. ACPA status is a delineator of RA disease endotype...

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Autores principales: Floudas, Achilleas, Canavan, Mary, McGarry, Trudy, Mullan, Ronan, Nagpal, Sunil, Veale, Douglas J., Fearon, Ursula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000255/
https://www.ncbi.nlm.nih.gov/pubmed/33799480
http://dx.doi.org/10.3390/cells10030647
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author Floudas, Achilleas
Canavan, Mary
McGarry, Trudy
Mullan, Ronan
Nagpal, Sunil
Veale, Douglas J.
Fearon, Ursula
author_facet Floudas, Achilleas
Canavan, Mary
McGarry, Trudy
Mullan, Ronan
Nagpal, Sunil
Veale, Douglas J.
Fearon, Ursula
author_sort Floudas, Achilleas
collection PubMed
description Rheumatoid arthritis (RA) is a progressive erosive autoimmune disease that affects 1% of the world population. Anti-citrullinated protein autoantibodies (ACPA) are routinely used for the diagnosis of RA, however 20–30% of patients are ACPA negative. ACPA status is a delineator of RA disease endotypes with similar clinical manifestation but potentially different pathophysiology. Profiling of key peripheral blood and synovial tissue immune populations including B cells, T follicular helper (Tfh) cells and CD4 T cell proinflammatory cytokine responses could elucidate the underlying immunological mechanisms involved and inform a treat to target approach for both ACPA-positive and ACPA-negative RA. Detailed high dimensionality flow cytometric analysis with supervised and unsupervised algorithm analysis revealed unique RA patient peripheral blood B cell and Tfh cell profiles. Synovial tissue single cell analysis of B cell subpopulation distribution was similar between ACPA− and ACPA+ RA patients, highlighting a key role for specific B cell subsets in both disease endotypes. Interestingly, synovial tissue single cell analysis of CD4 T cell proinflammatory cytokine production was markedly different between ACPA− and APCA+ RA patients. RNAseq analysis of RA patient synovial tissue highlighted disease endotype specific gene signatures. ACPA status associates with unique immune profile signatures that reinforce the need for a treat to target approach for both endotypes of RA.
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spelling pubmed-80002552021-03-28 ACPA Status Correlates with Differential Immune Profile in Patients with Rheumatoid Arthritis Floudas, Achilleas Canavan, Mary McGarry, Trudy Mullan, Ronan Nagpal, Sunil Veale, Douglas J. Fearon, Ursula Cells Article Rheumatoid arthritis (RA) is a progressive erosive autoimmune disease that affects 1% of the world population. Anti-citrullinated protein autoantibodies (ACPA) are routinely used for the diagnosis of RA, however 20–30% of patients are ACPA negative. ACPA status is a delineator of RA disease endotypes with similar clinical manifestation but potentially different pathophysiology. Profiling of key peripheral blood and synovial tissue immune populations including B cells, T follicular helper (Tfh) cells and CD4 T cell proinflammatory cytokine responses could elucidate the underlying immunological mechanisms involved and inform a treat to target approach for both ACPA-positive and ACPA-negative RA. Detailed high dimensionality flow cytometric analysis with supervised and unsupervised algorithm analysis revealed unique RA patient peripheral blood B cell and Tfh cell profiles. Synovial tissue single cell analysis of B cell subpopulation distribution was similar between ACPA− and ACPA+ RA patients, highlighting a key role for specific B cell subsets in both disease endotypes. Interestingly, synovial tissue single cell analysis of CD4 T cell proinflammatory cytokine production was markedly different between ACPA− and APCA+ RA patients. RNAseq analysis of RA patient synovial tissue highlighted disease endotype specific gene signatures. ACPA status associates with unique immune profile signatures that reinforce the need for a treat to target approach for both endotypes of RA. MDPI 2021-03-14 /pmc/articles/PMC8000255/ /pubmed/33799480 http://dx.doi.org/10.3390/cells10030647 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Floudas, Achilleas
Canavan, Mary
McGarry, Trudy
Mullan, Ronan
Nagpal, Sunil
Veale, Douglas J.
Fearon, Ursula
ACPA Status Correlates with Differential Immune Profile in Patients with Rheumatoid Arthritis
title ACPA Status Correlates with Differential Immune Profile in Patients with Rheumatoid Arthritis
title_full ACPA Status Correlates with Differential Immune Profile in Patients with Rheumatoid Arthritis
title_fullStr ACPA Status Correlates with Differential Immune Profile in Patients with Rheumatoid Arthritis
title_full_unstemmed ACPA Status Correlates with Differential Immune Profile in Patients with Rheumatoid Arthritis
title_short ACPA Status Correlates with Differential Immune Profile in Patients with Rheumatoid Arthritis
title_sort acpa status correlates with differential immune profile in patients with rheumatoid arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000255/
https://www.ncbi.nlm.nih.gov/pubmed/33799480
http://dx.doi.org/10.3390/cells10030647
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