Complete description of the three pathways of the complement system in a series of 430 patients with rheumatoid arthritis
The complement (C) system is implicated in the etiopathogenesis of rheumatoid arthritis (RA). However, there is a lack of studies characterizing all three C pathways in RA patients. This study aimed to evaluate the association between an in-depth examination of the C system and RA patient characteri...
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Data de publicação: | 2024 |
| País: | España |
| Recursos: | Universidad de Cantabria (UC) |
| Repositório: | UCrea Repositorio Abierto de la Universidad de Cantabria |
| Idioma: | inglês |
| OAI Identifier: | oai:repositorio.unican.es:10902/34462 |
| Acesso em linha: | https://hdl.handle.net/10902/34462 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Rheumatoid arthritis Complement system Complement pathways Complement activity assays Disease activity Rheumatoid factor Anti-citrullinated protein autoantibodies Inflammation |
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Complete description of the three pathways of the complement system in a series of 430 patients with rheumatoid arthritisRodríguez-González, DaraCarcía-González, MaríaGómez-Bernal, FuensantaQuevedo-Abeledo, Juan C.González-Rivero, Agustín F.Fernández-Cladera, YolandaGonzález López, ElenaOcejo-Vinyals, Javier GonzaloJiménez-Sosa, AlejandroGonzález-Toledo, BeatrizGonzález-Gay Mantecón, Miguel ÁngelRheumatoid arthritisComplement systemComplement pathwaysComplement activity assaysDisease activityRheumatoid factorAnti-citrullinated protein autoantibodiesInflammationThe complement (C) system is implicated in the etiopathogenesis of rheumatoid arthritis (RA). However, there is a lack of studies characterizing all three C pathways in RA patients. This study aimed to evaluate the association between an in-depth examination of the C system and RA patient characteristics, focusing on disease activity and the presence of rheumatoid factor and anti-citrullinated protein autoantibodies (ACPA). In a cohort of 430 RA patients, functional assays of the three C pathways (classical, alternative, and lectin) and serum levels of their components were assessed. Components included C1q (classical); factor D and properdin (alternative); lectin (lectin); C1-inhibitor; C2, C4, and C4b (classical and lectin); C3, C3a, and C4b (common); and C5, C5a, and C9 (terminal). A multivariable linear regression analysis showed significant positive correlations between C-reactive protein and C system proteins and functional assays, especially in the terminal and common pathways. Disease activity, measured by scores with or without acute phase reactants, positively correlated with the classical pathway functional test and terminal pathway products. Conversely, rheumatoid factor or ACPA presence was associated with lower classical pathway values and decreased C3a and C4b levels, suggesting complement depletion. In conclusion, RA disease activity increases C molecules and functional complement assays, while rheumatoid factor or ACPA positivity is linked to C consumption. Our study offers a detailed analysis of the complement system?s role in RA, potentially guiding the development of more targeted and effective treatment strategies.Funding: This study was funded by a grant to IF-A by Instituto de Salud Carlos III (ISCIII) through the project PI20/00084 and co-funded by the European Union. Acknowledgments: Iván Ferraz-Amaro would like to acknowledge that he has received grants/research supports from Abbott, MSD, Janssen, and Roche, as well as consultation fees from company-sponsored speakers’ bureaus associated with Abbott, Pfizer, Roche, Sanofi, Celgene, and M.A. González-Gay received consultation fees/participation from a company-sponsored speakers’ bureau from GSK.MDPIUniversidad de Cantabria20242024-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/34462International Journal of Molecular Sciences, 2024, 25, 8360reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/344622026-06-02T12:39:31Z |
| dc.title.none.fl_str_mv |
Complete description of the three pathways of the complement system in a series of 430 patients with rheumatoid arthritis |
| title |
Complete description of the three pathways of the complement system in a series of 430 patients with rheumatoid arthritis |
| spellingShingle |
Complete description of the three pathways of the complement system in a series of 430 patients with rheumatoid arthritis Rodríguez-González, Dara Rheumatoid arthritis Complement system Complement pathways Complement activity assays Disease activity Rheumatoid factor Anti-citrullinated protein autoantibodies Inflammation |
| title_short |
Complete description of the three pathways of the complement system in a series of 430 patients with rheumatoid arthritis |
| title_full |
Complete description of the three pathways of the complement system in a series of 430 patients with rheumatoid arthritis |
| title_fullStr |
Complete description of the three pathways of the complement system in a series of 430 patients with rheumatoid arthritis |
| title_full_unstemmed |
Complete description of the three pathways of the complement system in a series of 430 patients with rheumatoid arthritis |
| title_sort |
Complete description of the three pathways of the complement system in a series of 430 patients with rheumatoid arthritis |
| dc.creator.none.fl_str_mv |
Rodríguez-González, Dara Carcía-González, María Gómez-Bernal, Fuensanta Quevedo-Abeledo, Juan C. González-Rivero, Agustín F. Fernández-Cladera, Yolanda González López, Elena Ocejo-Vinyals, Javier Gonzalo Jiménez-Sosa, Alejandro González-Toledo, Beatriz González-Gay Mantecón, Miguel Ángel |
| author |
Rodríguez-González, Dara |
| author_facet |
Rodríguez-González, Dara Carcía-González, María Gómez-Bernal, Fuensanta Quevedo-Abeledo, Juan C. González-Rivero, Agustín F. Fernández-Cladera, Yolanda González López, Elena Ocejo-Vinyals, Javier Gonzalo Jiménez-Sosa, Alejandro González-Toledo, Beatriz González-Gay Mantecón, Miguel Ángel |
| author_role |
author |
| author2 |
Carcía-González, María Gómez-Bernal, Fuensanta Quevedo-Abeledo, Juan C. González-Rivero, Agustín F. Fernández-Cladera, Yolanda González López, Elena Ocejo-Vinyals, Javier Gonzalo Jiménez-Sosa, Alejandro González-Toledo, Beatriz González-Gay Mantecón, Miguel Ángel |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidad de Cantabria |
| dc.subject.none.fl_str_mv |
Rheumatoid arthritis Complement system Complement pathways Complement activity assays Disease activity Rheumatoid factor Anti-citrullinated protein autoantibodies Inflammation |
| topic |
Rheumatoid arthritis Complement system Complement pathways Complement activity assays Disease activity Rheumatoid factor Anti-citrullinated protein autoantibodies Inflammation |
| description |
The complement (C) system is implicated in the etiopathogenesis of rheumatoid arthritis (RA). However, there is a lack of studies characterizing all three C pathways in RA patients. This study aimed to evaluate the association between an in-depth examination of the C system and RA patient characteristics, focusing on disease activity and the presence of rheumatoid factor and anti-citrullinated protein autoantibodies (ACPA). In a cohort of 430 RA patients, functional assays of the three C pathways (classical, alternative, and lectin) and serum levels of their components were assessed. Components included C1q (classical); factor D and properdin (alternative); lectin (lectin); C1-inhibitor; C2, C4, and C4b (classical and lectin); C3, C3a, and C4b (common); and C5, C5a, and C9 (terminal). A multivariable linear regression analysis showed significant positive correlations between C-reactive protein and C system proteins and functional assays, especially in the terminal and common pathways. Disease activity, measured by scores with or without acute phase reactants, positively correlated with the classical pathway functional test and terminal pathway products. Conversely, rheumatoid factor or ACPA presence was associated with lower classical pathway values and decreased C3a and C4b levels, suggesting complement depletion. In conclusion, RA disease activity increases C molecules and functional complement assays, while rheumatoid factor or ACPA positivity is linked to C consumption. Our study offers a detailed analysis of the complement system?s role in RA, potentially guiding the development of more targeted and effective treatment strategies. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024-01-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 NA http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10902/34462 |
| url |
https://hdl.handle.net/10902/34462 |
| 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 Attribution 4.0 International http://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 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
| dc.publisher.none.fl_str_mv |
MDPI |
| publisher.none.fl_str_mv |
MDPI |
| dc.source.none.fl_str_mv |
International Journal of Molecular Sciences, 2024, 25, 8360 reponame:UCrea Repositorio Abierto de la Universidad de Cantabria instname:Universidad de Cantabria (UC) |
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Universidad de Cantabria (UC) |
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UCrea Repositorio Abierto de la Universidad de Cantabria |
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UCrea Repositorio Abierto de la Universidad de Cantabria |
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