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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| Tipo de documento: | Artículo |
| Estado: | Published version |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p9101 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9101 |
| Nivel de acceso: | Acceso abierto |
| _version_ | 1878741086922342400 |
|---|---|
| author | Zamora-Atenza, C |
| 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 |
| author_browse | Canto, E Casademont, J Castellvi, I Diaz-Lopez, C Diaz-Torne, C Geli, C Juarez, C Llobet, JM Moya, P Nieto, JC Ortiz, MA Vidal, S 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 |
| collection | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_ded9b4c3ca083dc2e67dfb00a29b19e6 |
| institution | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| instname_str | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:iibsantpau.fundanetsuite.com:p9101 |
| publishDate | 2014 |
| publishDateSort | 2014 |
| publisher | BMC |
| publisherStr | BMC |
| reponame_str | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| spelling | Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis 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 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. BMC https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9101 |
| spellingShingle | Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis Zamora-Atenza, C |
| status_str | publishedVersion |
| title | 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_short | Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis |
| title_sort | Adalimumab regulates intracellular TNF alpha production in patients with rheumatoid arthritis |
| url | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9101 |