High levels of natural killer cells are associated with response to tocilizumab in patients with severe rheumatoid arthritis
We aimed to assess the effect of tocilizumab (TCZ), an IL-6 receptor inhibitor, on B, T, NK and NKT cells in patients with RA and to study the cell type predictors of remission. We also compared NK cells in patients with RA and in controls. RA patients included in the study met the 2010 ACR/European...
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| Veröffentlicht in: | Rheumatology 2015-04, Vol.54 (4), p.601-608 |
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| creator | Daïen, Claire Immediato Gailhac, Sarah Audo, Rachel Mura, Thibault Hahne, Michael Combe, Bernard Morel, Jacques |
| description | We aimed to assess the effect of tocilizumab (TCZ), an IL-6 receptor inhibitor, on B, T, NK and NKT cells in patients with RA and to study the cell type predictors of remission. We also compared NK cells in patients with RA and in controls.
RA patients included in the study met the 2010 ACR/European League Against Rheumatism (EULAR) criteria, were receiving stable doses of steroids and had not received rituximab in the previous year. Different B and T cell subsets, NK cells and NKT cells were assessed by flow cytometry along with perforin A and granzyme B to estimate NK cell cytotoxicity.
We included 92 RA patients, including 20 requiring TCZ treatment and 15 requiring anti-TNF drugs, and 25 controls. At baseline, the proportion of CD56(dim)CD16(+)CD3(-) NK cells was inversely correlated with the 28-joint DAS (DAS28). In TCZ-treated patients, the baseline proportion of CD3(-)CD56(+) NK cells was inversely correlated with the change in DAS28 at 3 months and the proportion was 3-fold greater for patients with DAS28 remission at 3 months than other patients. Change in the proportion of CD56(bri)CD16(-) NK cells was linearly correlated with change in the DAS28 at 3 months. The baseline proportion of NK cells did not predict change in disease activity at 3 months with anti-TNF therapy. The perforin content in NK cells increased with TCZ treatment.
This study supports NK cell involvement in RA and in the TCZ mechanism of action. NK cells at baseline could be a predictive factor of TCZ response if results are confirmed. |
| doi_str_mv | 10.1093/rheumatology/keu363 |
| format | Article |
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RA patients included in the study met the 2010 ACR/European League Against Rheumatism (EULAR) criteria, were receiving stable doses of steroids and had not received rituximab in the previous year. Different B and T cell subsets, NK cells and NKT cells were assessed by flow cytometry along with perforin A and granzyme B to estimate NK cell cytotoxicity.
We included 92 RA patients, including 20 requiring TCZ treatment and 15 requiring anti-TNF drugs, and 25 controls. At baseline, the proportion of CD56(dim)CD16(+)CD3(-) NK cells was inversely correlated with the 28-joint DAS (DAS28). In TCZ-treated patients, the baseline proportion of CD3(-)CD56(+) NK cells was inversely correlated with the change in DAS28 at 3 months and the proportion was 3-fold greater for patients with DAS28 remission at 3 months than other patients. Change in the proportion of CD56(bri)CD16(-) NK cells was linearly correlated with change in the DAS28 at 3 months. The baseline proportion of NK cells did not predict change in disease activity at 3 months with anti-TNF therapy. The perforin content in NK cells increased with TCZ treatment.
This study supports NK cell involvement in RA and in the TCZ mechanism of action. NK cells at baseline could be a predictive factor of TCZ response if results are confirmed.</description><identifier>ISSN: 1462-0324</identifier><identifier>EISSN: 1462-0332</identifier><identifier>EISSN: 1460-2172</identifier><identifier>DOI: 10.1093/rheumatology/keu363</identifier><identifier>PMID: 25231180</identifier><language>eng</language><publisher>England: Oxford University Press (OUP)</publisher><subject>Adalimumab ; Adult ; Aged ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antirheumatic Agents - therapeutic use ; Arthritis, Rheumatoid - drug therapy ; Arthritis, Rheumatoid - immunology ; Certolizumab Pegol ; Etanercept ; Female ; Human health and pathology ; Humans ; Immunoglobulin Fab Fragments - therapeutic use ; Immunoglobulin G - therapeutic use ; Killer Cells, Natural - immunology ; Life Sciences ; Male ; Middle Aged ; Polyethylene Glycols - therapeutic use ; Prospective Studies ; Receptors, Interleukin-6 - antagonists & inhibitors ; Receptors, Tumor Necrosis Factor - therapeutic use ; Rhumatology and musculoskeletal system ; Severity of Illness Index ; Treatment Outcome ; Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><ispartof>Rheumatology, 2015-04, Vol.54 (4), p.601-608</ispartof><rights>The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-ee79df1377b6ab0d3489026eec926b514bb78c2904b68983034302828e170cea3</citedby><cites>FETCH-LOGICAL-c384t-ee79df1377b6ab0d3489026eec926b514bb78c2904b68983034302828e170cea3</cites><orcidid>0000-0001-7545-6385 ; 0000-0001-6420-1336</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25231180$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.umontpellier.fr/hal-02273925$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Daïen, Claire Immediato</creatorcontrib><creatorcontrib>Gailhac, Sarah</creatorcontrib><creatorcontrib>Audo, Rachel</creatorcontrib><creatorcontrib>Mura, Thibault</creatorcontrib><creatorcontrib>Hahne, Michael</creatorcontrib><creatorcontrib>Combe, Bernard</creatorcontrib><creatorcontrib>Morel, Jacques</creatorcontrib><title>High levels of natural killer cells are associated with response to tocilizumab in patients with severe rheumatoid arthritis</title><title>Rheumatology</title><addtitle>Rheumatology (Oxford)</addtitle><description>We aimed to assess the effect of tocilizumab (TCZ), an IL-6 receptor inhibitor, on B, T, NK and NKT cells in patients with RA and to study the cell type predictors of remission. We also compared NK cells in patients with RA and in controls.
RA patients included in the study met the 2010 ACR/European League Against Rheumatism (EULAR) criteria, were receiving stable doses of steroids and had not received rituximab in the previous year. Different B and T cell subsets, NK cells and NKT cells were assessed by flow cytometry along with perforin A and granzyme B to estimate NK cell cytotoxicity.
We included 92 RA patients, including 20 requiring TCZ treatment and 15 requiring anti-TNF drugs, and 25 controls. At baseline, the proportion of CD56(dim)CD16(+)CD3(-) NK cells was inversely correlated with the 28-joint DAS (DAS28). In TCZ-treated patients, the baseline proportion of CD3(-)CD56(+) NK cells was inversely correlated with the change in DAS28 at 3 months and the proportion was 3-fold greater for patients with DAS28 remission at 3 months than other patients. Change in the proportion of CD56(bri)CD16(-) NK cells was linearly correlated with change in the DAS28 at 3 months. The baseline proportion of NK cells did not predict change in disease activity at 3 months with anti-TNF therapy. The perforin content in NK cells increased with TCZ treatment.
This study supports NK cell involvement in RA and in the TCZ mechanism of action. NK cells at baseline could be a predictive factor of TCZ response if results are confirmed.</description><subject>Adalimumab</subject><subject>Adult</subject><subject>Aged</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Antirheumatic Agents - therapeutic use</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Certolizumab Pegol</subject><subject>Etanercept</subject><subject>Female</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Immunoglobulin Fab Fragments - therapeutic use</subject><subject>Immunoglobulin G - therapeutic use</subject><subject>Killer Cells, Natural - immunology</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Polyethylene Glycols - therapeutic use</subject><subject>Prospective Studies</subject><subject>Receptors, Interleukin-6 - antagonists & inhibitors</subject><subject>Receptors, Tumor Necrosis Factor - therapeutic use</subject><subject>Rhumatology and musculoskeletal system</subject><subject>Severity of Illness Index</subject><subject>Treatment Outcome</subject><subject>Tumor Necrosis Factor-alpha - antagonists & inhibitors</subject><issn>1462-0324</issn><issn>1462-0332</issn><issn>1460-2172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkUFrGzEQhUVoSFInv6BQdGwOTiTNrlZ7DKGpC4ZckrPQ7o69quWVK2lTHPrjI7OJCQhGDN97M8wj5BtnN5zVcBt6HLcmeefX-9sNjiDhhFzwQoo5AxBfjn9RnJOvMf5hjJUc1Bk5F6UAzhW7IP8Xdt1Thy_oIvUrOpg0BuPoxjqHgbboct8EpCZG31qTsKP_bOppwLjzQ0SafH6tdfY1b9NQO9CdSRaHFCcwZu-s_9jWdtku9cEmGy_J6cq4iFfvdUaeH34-3S_my8dfv-_vlvMWVJHmiFXdrThUVSNNwzooVM2ERGxrIZuSF01TqVbUrGikqhUwKIAJJRTyirVoYEauJ9_eOL0LdmvCXntj9eJuqQ89JkQFtShfeGZ_TOwu-L8jxqS3Nh7OYAb0Y9RcygpKLkWdUZjQNvgYA66O3pzpQ0T6c0R6iiirvr8PGJstdkfNRybwBq3GkyE</recordid><startdate>201504</startdate><enddate>201504</enddate><creator>Daïen, Claire Immediato</creator><creator>Gailhac, Sarah</creator><creator>Audo, Rachel</creator><creator>Mura, Thibault</creator><creator>Hahne, Michael</creator><creator>Combe, Bernard</creator><creator>Morel, Jacques</creator><general>Oxford University Press (OUP)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-7545-6385</orcidid><orcidid>https://orcid.org/0000-0001-6420-1336</orcidid></search><sort><creationdate>201504</creationdate><title>High levels of natural killer cells are associated with response to tocilizumab in patients with severe rheumatoid arthritis</title><author>Daïen, Claire Immediato ; Gailhac, Sarah ; Audo, Rachel ; Mura, Thibault ; Hahne, Michael ; Combe, Bernard ; Morel, Jacques</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-ee79df1377b6ab0d3489026eec926b514bb78c2904b68983034302828e170cea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adalimumab</topic><topic>Adult</topic><topic>Aged</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>Antirheumatic Agents - therapeutic use</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Certolizumab Pegol</topic><topic>Etanercept</topic><topic>Female</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Immunoglobulin Fab Fragments - therapeutic use</topic><topic>Immunoglobulin G - therapeutic use</topic><topic>Killer Cells, Natural - immunology</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Polyethylene Glycols - therapeutic use</topic><topic>Prospective Studies</topic><topic>Receptors, Interleukin-6 - antagonists & inhibitors</topic><topic>Receptors, Tumor Necrosis Factor - therapeutic use</topic><topic>Rhumatology and musculoskeletal system</topic><topic>Severity of Illness Index</topic><topic>Treatment Outcome</topic><topic>Tumor Necrosis Factor-alpha - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Daïen, Claire Immediato</creatorcontrib><creatorcontrib>Gailhac, Sarah</creatorcontrib><creatorcontrib>Audo, Rachel</creatorcontrib><creatorcontrib>Mura, Thibault</creatorcontrib><creatorcontrib>Hahne, Michael</creatorcontrib><creatorcontrib>Combe, Bernard</creatorcontrib><creatorcontrib>Morel, Jacques</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Rheumatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Daïen, Claire Immediato</au><au>Gailhac, Sarah</au><au>Audo, Rachel</au><au>Mura, Thibault</au><au>Hahne, Michael</au><au>Combe, Bernard</au><au>Morel, Jacques</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High levels of natural killer cells are associated with response to tocilizumab in patients with severe rheumatoid arthritis</atitle><jtitle>Rheumatology</jtitle><addtitle>Rheumatology (Oxford)</addtitle><date>2015-04</date><risdate>2015</risdate><volume>54</volume><issue>4</issue><spage>601</spage><epage>608</epage><pages>601-608</pages><issn>1462-0324</issn><eissn>1462-0332</eissn><eissn>1460-2172</eissn><abstract>We aimed to assess the effect of tocilizumab (TCZ), an IL-6 receptor inhibitor, on B, T, NK and NKT cells in patients with RA and to study the cell type predictors of remission. We also compared NK cells in patients with RA and in controls.
RA patients included in the study met the 2010 ACR/European League Against Rheumatism (EULAR) criteria, were receiving stable doses of steroids and had not received rituximab in the previous year. Different B and T cell subsets, NK cells and NKT cells were assessed by flow cytometry along with perforin A and granzyme B to estimate NK cell cytotoxicity.
We included 92 RA patients, including 20 requiring TCZ treatment and 15 requiring anti-TNF drugs, and 25 controls. At baseline, the proportion of CD56(dim)CD16(+)CD3(-) NK cells was inversely correlated with the 28-joint DAS (DAS28). In TCZ-treated patients, the baseline proportion of CD3(-)CD56(+) NK cells was inversely correlated with the change in DAS28 at 3 months and the proportion was 3-fold greater for patients with DAS28 remission at 3 months than other patients. Change in the proportion of CD56(bri)CD16(-) NK cells was linearly correlated with change in the DAS28 at 3 months. The baseline proportion of NK cells did not predict change in disease activity at 3 months with anti-TNF therapy. The perforin content in NK cells increased with TCZ treatment.
This study supports NK cell involvement in RA and in the TCZ mechanism of action. NK cells at baseline could be a predictive factor of TCZ response if results are confirmed.</abstract><cop>England</cop><pub>Oxford University Press (OUP)</pub><pmid>25231180</pmid><doi>10.1093/rheumatology/keu363</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-7545-6385</orcidid><orcidid>https://orcid.org/0000-0001-6420-1336</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Rheumatology, 2015-04, Vol.54 (4), p.601-608 |
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| language | eng |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Adalimumab Adult Aged Antibodies, Monoclonal, Humanized - therapeutic use Antirheumatic Agents - therapeutic use Arthritis, Rheumatoid - drug therapy Arthritis, Rheumatoid - immunology Certolizumab Pegol Etanercept Female Human health and pathology Humans Immunoglobulin Fab Fragments - therapeutic use Immunoglobulin G - therapeutic use Killer Cells, Natural - immunology Life Sciences Male Middle Aged Polyethylene Glycols - therapeutic use Prospective Studies Receptors, Interleukin-6 - antagonists & inhibitors Receptors, Tumor Necrosis Factor - therapeutic use Rhumatology and musculoskeletal system Severity of Illness Index Treatment Outcome Tumor Necrosis Factor-alpha - antagonists & inhibitors |
| title | High levels of natural killer cells are associated with response to tocilizumab in patients with severe rheumatoid arthritis |
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