Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis

Background: Platelets (PLTs) from healthy donors (HD) modulate T lymphocyte responses but PLTs from rheumatoid arthritis (RA) patients contribute to persistent systemic inflammation. This suggests that PLTs from RA patients and HD have different immunomodulatory effects. Methods: Using cell culture,...

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Authors: Zamora, Carlos|||0000-0003-2962-678X, Diaz-Torne, Cesar|||0000-0001-6275-7699, Ortiz, M. Àngels|||0000-0002-1574-9861, Moya, Patricia|||0000-0001-8339-5420, Park, Hye S.|||0000-0002-4972-9527, Pitarch, C., Cantó, Elisabet|||0000-0002-1782-1855, Osuna Gómez, Rubén|||0000-0003-2875-4405, Mulet Gual, Maria|||0000-0003-3639-3291, García-Arguinzonis, Maisa|||0000-0001-6749-5026, Collado, D., Corominas, Hèctor|||0000-0002-7738-6787, Vidal, Silvia|||0000-0002-3909-6682
Format: article
Publication Date:2025
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:322589
Online Access:https://ddd.uab.cat/record/322589
https://dx.doi.org/urn:doi:10.3390/cells14090625
Access Level:Open access
Keyword:CD40L
T lymphocyte activation
Cytokine production
Platelet immunomodulation
Rheumatoid arthritis
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spelling Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid ArthritisZamora, Carlos|||0000-0003-2962-678XDiaz-Torne, Cesar|||0000-0001-6275-7699Ortiz, M. Àngels|||0000-0002-1574-9861Moya, Patricia|||0000-0001-8339-5420Park, Hye S.|||0000-0002-4972-9527Pitarch, C.Cantó, Elisabet|||0000-0002-1782-1855Osuna Gómez, Rubén|||0000-0003-2875-4405Mulet Gual, Maria|||0000-0003-3639-3291García-Arguinzonis, Maisa|||0000-0001-6749-5026Collado, D.Corominas, Hèctor|||0000-0002-7738-6787Vidal, Silvia|||0000-0002-3909-6682CD40LT lymphocyte activationCytokine productionPlatelet immunomodulationRheumatoid arthritisBackground: Platelets (PLTs) from healthy donors (HD) modulate T lymphocyte responses but PLTs from rheumatoid arthritis (RA) patients contribute to persistent systemic inflammation. This suggests that PLTs from RA patients and HD have different immunomodulatory effects. Methods: Using cell culture, flow cytometry, proteomics, and ELISA, we compared PLTs from HD and RA patients and their effects on T lymphocyte activation and cytokine production. Results: HD PLTs suppressed T lymphocyte proliferation and IFNγ and TNF production, while RA PLTs exhibited reduced suppressive capacity. In the presence of RA PLTs, IFNγ levels correlated with T lymphocyte proliferation, greater disease activity, and anti-citrullinated protein antibodies (ACPA). Proteomic analysis revealed that RA PLTs show upregulation of proteins linked to acute-phase response and complement activation. RA PLTs secreted higher levels of soluble CD40L (sCD40L) and PDGF-BB that correlated with enhanced IFNγ production. Seropositive RA patients had higher levels of sCD40L, and these levels were predictive of disease remission in RA patients treated with anti-IL6R. sCD40L was found to enhance T lymphocyte activation and to contribute to increased pro-inflammatory cytokine production. Conclusions: This study highlights the diminished ability of RA PLTs to suppress T lymphocyte activation and that sCD40L can be a potential biomarker and therapeutic target in RA.Universitat Autònoma de Barcelona. Departament de Medicina 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/322589https://dx.doi.org/urn:doi:10.3390/cells14090625reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:3225892026-06-06T12:50:31Z
dc.title.none.fl_str_mv Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis
title Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis
spellingShingle Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis
Zamora, Carlos|||0000-0003-2962-678X
CD40L
T lymphocyte activation
Cytokine production
Platelet immunomodulation
Rheumatoid arthritis
title_short Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis
title_full Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis
title_fullStr Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis
title_full_unstemmed Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis
title_sort Platelet-Derived Soluble CD40L and Its Impact on Immune Modulation and Anti-IL6R Antibody Treatment Outcome in Rheumatoid Arthritis
dc.creator.none.fl_str_mv Zamora, Carlos|||0000-0003-2962-678X
Diaz-Torne, Cesar|||0000-0001-6275-7699
Ortiz, M. Àngels|||0000-0002-1574-9861
Moya, Patricia|||0000-0001-8339-5420
Park, Hye S.|||0000-0002-4972-9527
Pitarch, C.
Cantó, Elisabet|||0000-0002-1782-1855
Osuna Gómez, Rubén|||0000-0003-2875-4405
Mulet Gual, Maria|||0000-0003-3639-3291
García-Arguinzonis, Maisa|||0000-0001-6749-5026
Collado, D.
Corominas, Hèctor|||0000-0002-7738-6787
Vidal, Silvia|||0000-0002-3909-6682
author Zamora, Carlos|||0000-0003-2962-678X
author_facet Zamora, Carlos|||0000-0003-2962-678X
Diaz-Torne, Cesar|||0000-0001-6275-7699
Ortiz, M. Àngels|||0000-0002-1574-9861
Moya, Patricia|||0000-0001-8339-5420
Park, Hye S.|||0000-0002-4972-9527
Pitarch, C.
Cantó, Elisabet|||0000-0002-1782-1855
Osuna Gómez, Rubén|||0000-0003-2875-4405
Mulet Gual, Maria|||0000-0003-3639-3291
García-Arguinzonis, Maisa|||0000-0001-6749-5026
Collado, D.
Corominas, Hèctor|||0000-0002-7738-6787
Vidal, Silvia|||0000-0002-3909-6682
author_role author
author2 Diaz-Torne, Cesar|||0000-0001-6275-7699
Ortiz, M. Àngels|||0000-0002-1574-9861
Moya, Patricia|||0000-0001-8339-5420
Park, Hye S.|||0000-0002-4972-9527
Pitarch, C.
Cantó, Elisabet|||0000-0002-1782-1855
Osuna Gómez, Rubén|||0000-0003-2875-4405
Mulet Gual, Maria|||0000-0003-3639-3291
García-Arguinzonis, Maisa|||0000-0001-6749-5026
Collado, D.
Corominas, Hèctor|||0000-0002-7738-6787
Vidal, Silvia|||0000-0002-3909-6682
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona. Departament de Medicina
dc.subject.none.fl_str_mv CD40L
T lymphocyte activation
Cytokine production
Platelet immunomodulation
Rheumatoid arthritis
topic CD40L
T lymphocyte activation
Cytokine production
Platelet immunomodulation
Rheumatoid arthritis
description Background: Platelets (PLTs) from healthy donors (HD) modulate T lymphocyte responses but PLTs from rheumatoid arthritis (RA) patients contribute to persistent systemic inflammation. This suggests that PLTs from RA patients and HD have different immunomodulatory effects. Methods: Using cell culture, flow cytometry, proteomics, and ELISA, we compared PLTs from HD and RA patients and their effects on T lymphocyte activation and cytokine production. Results: HD PLTs suppressed T lymphocyte proliferation and IFNγ and TNF production, while RA PLTs exhibited reduced suppressive capacity. In the presence of RA PLTs, IFNγ levels correlated with T lymphocyte proliferation, greater disease activity, and anti-citrullinated protein antibodies (ACPA). Proteomic analysis revealed that RA PLTs show upregulation of proteins linked to acute-phase response and complement activation. RA PLTs secreted higher levels of soluble CD40L (sCD40L) and PDGF-BB that correlated with enhanced IFNγ production. Seropositive RA patients had higher levels of sCD40L, and these levels were predictive of disease remission in RA patients treated with anti-IL6R. sCD40L was found to enhance T lymphocyte activation and to contribute to increased pro-inflammatory cytokine production. Conclusions: This study highlights the diminished ability of RA PLTs to suppress T lymphocyte activation and that sCD40L can be a potential biomarker and therapeutic target in RA.
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/322589
https://dx.doi.org/urn:doi:10.3390/cells14090625
url https://ddd.uab.cat/record/322589
https://dx.doi.org/urn:doi:10.3390/cells14090625
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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