Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis

Introduction: Adalimumab is a fully human anti-tumor necrosis factor a (anti-TNF alpha) monoclonal antibody that specifically blocks the interaction of TNF alpha with its receptors. It binds both soluble and transmembrane TNF alpha. We hypothesized that blocking these TNF alpha signals regulates the...

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Autores: Zamora-Atenza, C, Diaz-Torne, C, Geli, C, Diaz-Lopez, C, Ortiz, MA, Moya, P, Castellvi, I, Nieto, JC, Canto, E, Casademont, J, Juarez, C, Llobet, JM, Vidal, S
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2014
País:España
Recursos:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositório:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p9101
Acesso em linha:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9101
Access Level:Acceso aberto
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spelling Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritisZamora-Atenza, CDiaz-Torne, CGeli, CDiaz-Lopez, COrtiz, MAMoya, PCastellvi, INieto, JCCanto, ECasademont, JJuarez, CLlobet, JMVidal, SIntroduction: Adalimumab is a fully human anti-tumor necrosis factor a (anti-TNF alpha) monoclonal antibody that specifically blocks the interaction of TNF alpha with its receptors. It binds both soluble and transmembrane TNF alpha. We hypothesized that blocking these TNF alpha signals regulates the altered TNF alpha production in rheumatoid arthritis (RA) patients. Methods: We compared, by flow cytometry, Toll-like receptor induction levels of membrane and intracellular TNF alpha in monocytes (iTNF alpha + CD14+ cells) from 12 patients before and after adalimumab treatment with those from 5 healthy donors. Results: Before starting the treatment, the percentage of iTNF alpha+ CD14+ cells in the RA patients was significantly lower than that in healthy donors (mean +/- SEM = 33.16 +/- 4.82% vs 66.51 +/- 2.4%, P < 0.001). When we added in vitro TNF alpha to healthy donor culture cells, levels of iTNF alpha+ CD14+ cells decreased, suggesting that the TNF alpha signal was responsible for the iTNF alpha+ CD14+ cell downregulation observed in the RA patients. After 2, 6 and 12 adalimumab injections, we observed significant blocking of membrane and soluble TNF alpha and a progressive increase in iTNF alpha+ CD14+ cells in ten patients with a good to moderate response as defined by the European League Against Rheumatism (EULAR) criteria. Levels of iTNF alpha+ CD14+ cells after 12 injections in these 10 patients were comparable to levels in healthy donors. In two patients, iTNF alpha+ CD14+ cell upregulation was not observed, and their EULAR-defined responses had not improved. The first patient developed antiadalimumab antibodies, explaining why adalimumab was not able to block membrane and soluble TNF alpha. In the second patient, adalimumab was discontinued because of adverse effects, which led to a decrease in iTNF alpha+ CD14+ cells to levels measured before treatment. Conclusions: Our findings suggest that adalimumab treatment in RA patients can return iTNF alpha levels to those of healthy donors. This effect was not observed in the presence of neutralizing antiadalimumab antibodies.BMC2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9101ARTHRITIS RESEARCH & THERAPYISSN: 14786354ISSNe: 14786362reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p91012026-06-14T12:41:47Z
dc.title.none.fl_str_mv Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis
title Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis
spellingShingle Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis
Zamora-Atenza, C
title_short Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis
title_full Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis
title_fullStr Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis
title_full_unstemmed Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis
title_sort Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis
dc.creator.none.fl_str_mv Zamora-Atenza, C
Diaz-Torne, C
Geli, C
Diaz-Lopez, C
Ortiz, MA
Moya, P
Castellvi, I
Nieto, JC
Canto, E
Casademont, J
Juarez, C
Llobet, JM
Vidal, S
author Zamora-Atenza, C
author_facet Zamora-Atenza, C
Diaz-Torne, C
Geli, C
Diaz-Lopez, C
Ortiz, MA
Moya, P
Castellvi, I
Nieto, JC
Canto, E
Casademont, J
Juarez, C
Llobet, JM
Vidal, S
author_role author
author2 Diaz-Torne, C
Geli, C
Diaz-Lopez, C
Ortiz, MA
Moya, P
Castellvi, I
Nieto, JC
Canto, E
Casademont, J
Juarez, C
Llobet, JM
Vidal, S
author2_role author
author
author
author
author
author
author
author
author
author
author
author
description Introduction: Adalimumab is a fully human anti-tumor necrosis factor a (anti-TNF alpha) monoclonal antibody that specifically blocks the interaction of TNF alpha with its receptors. It binds both soluble and transmembrane TNF alpha. We hypothesized that blocking these TNF alpha signals regulates the altered TNF alpha production in rheumatoid arthritis (RA) patients. Methods: We compared, by flow cytometry, Toll-like receptor induction levels of membrane and intracellular TNF alpha in monocytes (iTNF alpha + CD14+ cells) from 12 patients before and after adalimumab treatment with those from 5 healthy donors. Results: Before starting the treatment, the percentage of iTNF alpha+ CD14+ cells in the RA patients was significantly lower than that in healthy donors (mean +/- SEM = 33.16 +/- 4.82% vs 66.51 +/- 2.4%, P < 0.001). When we added in vitro TNF alpha to healthy donor culture cells, levels of iTNF alpha+ CD14+ cells decreased, suggesting that the TNF alpha signal was responsible for the iTNF alpha+ CD14+ cell downregulation observed in the RA patients. After 2, 6 and 12 adalimumab injections, we observed significant blocking of membrane and soluble TNF alpha and a progressive increase in iTNF alpha+ CD14+ cells in ten patients with a good to moderate response as defined by the European League Against Rheumatism (EULAR) criteria. Levels of iTNF alpha+ CD14+ cells after 12 injections in these 10 patients were comparable to levels in healthy donors. In two patients, iTNF alpha+ CD14+ cell upregulation was not observed, and their EULAR-defined responses had not improved. The first patient developed antiadalimumab antibodies, explaining why adalimumab was not able to block membrane and soluble TNF alpha. In the second patient, adalimumab was discontinued because of adverse effects, which led to a decrease in iTNF alpha+ CD14+ cells to levels measured before treatment. Conclusions: Our findings suggest that adalimumab treatment in RA patients can return iTNF alpha levels to those of healthy donors. This effect was not observed in the presence of neutralizing antiadalimumab antibodies.
publishDate 2014
dc.date.none.fl_str_mv 2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9101
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9101
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv ARTHRITIS RESEARCH & THERAPY
ISSN: 14786354
ISSNe: 14786362
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
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instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
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