A3.3 An Immunological Window of Opportunity Defines the Ability of Early RA Patient to Achieve Remission with First Anti-Rheumatic Treatment

Background and Objectives The therapeutic goal for patients with rheumatoid arthritis (RA) is clinical remission. This is best achieved by early diagnosis followed by appropriate therapeutic intervention. RA is associated with dys-regulation of T-cell subsets early in the disease with naïve cells an...

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Veröffentlicht in:Annals of the rheumatic diseases 2013-03, Vol.72 (Suppl 1), p.A14
Hauptverfasser: Burska, Agata, Parmar, Rekha, El-Sherbiny, Yasser, El Jawhari, Jehan, Emery, Paul, Ponchel, Frederique
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container_issue Suppl 1
container_start_page A14
container_title Annals of the rheumatic diseases
container_volume 72
creator Burska, Agata
Parmar, Rekha
El-Sherbiny, Yasser
El Jawhari, Jehan
Emery, Paul
Ponchel, Frederique
description Background and Objectives The therapeutic goal for patients with rheumatoid arthritis (RA) is clinical remission. This is best achieved by early diagnosis followed by appropriate therapeutic intervention. RA is associated with dys-regulation of T-cell subsets early in the disease with naïve cells and regulatory T-cell losses and acquisition of abnormal subset in realtion with inflammation (IRC). Our aim was to test the hypothesis that T-cell subset quantification can predict the achievement of clinical remission in patients with early RA. Materials and Methods T-cell subsets (naive, Treg and IRC) were quantified using flow cytometry in 108 DMARDs-naïve, early RA patients (
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This is best achieved by early diagnosis followed by appropriate therapeutic intervention. RA is associated with dys-regulation of T-cell subsets early in the disease with naïve cells and regulatory T-cell losses and acquisition of abnormal subset in realtion with inflammation (IRC). Our aim was to test the hypothesis that T-cell subset quantification can predict the achievement of clinical remission in patients with early RA. Materials and Methods T-cell subsets (naive, Treg and IRC) were quantified using flow cytometry in 108 DMARDs-naïve, early RA patients (&lt;24 months) symptom duration commencing methot-rexate MTX or MTX + anti-tumour necrosis factor agents (anti-TNF) and in 105 healthy controls (HC). The primary outcome assessed was remission (DAS28 &lt; 2.6). The pilot analysis was performed on frozen PBMC obtained from 38 RA patients and 35 HC. These results were validated using fresh blood samples on a cohort of 70 RA patients and 70 HC. Results In the pilot study, T-cell subset analysis in early RA confirmed immune dysregulation compared to HC with reduced frequency of naïve CD4+ T-cells and Treg and increased IRC (all p &lt; 0.001) compared to HC. Naive T-cell above median was associated with remission (p = 0.001). In the validation study, 50 patients were treated with MTX and showed the same relationship with naïve cell frequency above median being associated with remission (p = 0.011). Individual analysis on each patient’s naïve cell frequency deviation from expected (using 70 HC) demonstrated that “normal” naïve cell frequency (observed in 30 patients) was associated with remission whereas reduced naïve cell frequency was more frequently observed in patients with poor response to MTX (p = 0.03). Patients with poor immunological status were not prevented to achieve remission when treated with MTX + anti-TNF (n = 20 including 10 patients with normal and 10 with reduced naïve cells) raising the rate of remission from 20% in the MTX group (n = 4 of the 20 patients with reduced naïve cells at baseline) to 60% in the MTX + anti-TNF group (n = 6 of the 10 patients). Conclusions These data show that baseline naïve T-cell subset analysis has a value in predicting early RA MTX treatment outcome. Immunological analysis could be used in conjunction with clinical/serological features to predict response to MTX and select the most appropriate therapy at disease presentation.</description><identifier>ISSN: 0003-4967</identifier><identifier>EISSN: 1468-2060</identifier><identifier>DOI: 10.1136/annrheumdis-2013-203216.3</identifier><identifier>CODEN: ARDIAO</identifier><language>eng</language><publisher>Kidlington: BMJ Publishing Group Ltd and European League Against Rheumatism</publisher><ispartof>Annals of the rheumatic diseases, 2013-03, Vol.72 (Suppl 1), p.A14</ispartof><rights>2013, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Copyright: 2013 (c) 2013, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b2683-9d04bcfde4e2164f5bf30102d8d3928a133697f84429408c082d0df4132ecfe93</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://ard.bmj.com/content/72/Suppl_1/A14.1.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://ard.bmj.com/content/72/Suppl_1/A14.1.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,776,780,3183,23550,27901,27902,77342,77373</link.rule.ids></links><search><creatorcontrib>Burska, Agata</creatorcontrib><creatorcontrib>Parmar, Rekha</creatorcontrib><creatorcontrib>El-Sherbiny, Yasser</creatorcontrib><creatorcontrib>El Jawhari, Jehan</creatorcontrib><creatorcontrib>Emery, Paul</creatorcontrib><creatorcontrib>Ponchel, Frederique</creatorcontrib><title>A3.3 An Immunological Window of Opportunity Defines the Ability of Early RA Patient to Achieve Remission with First Anti-Rheumatic Treatment</title><title>Annals of the rheumatic diseases</title><addtitle>Ann Rheum Dis</addtitle><description>Background and Objectives The therapeutic goal for patients with rheumatoid arthritis (RA) is clinical remission. This is best achieved by early diagnosis followed by appropriate therapeutic intervention. RA is associated with dys-regulation of T-cell subsets early in the disease with naïve cells and regulatory T-cell losses and acquisition of abnormal subset in realtion with inflammation (IRC). Our aim was to test the hypothesis that T-cell subset quantification can predict the achievement of clinical remission in patients with early RA. Materials and Methods T-cell subsets (naive, Treg and IRC) were quantified using flow cytometry in 108 DMARDs-naïve, early RA patients (&lt;24 months) symptom duration commencing methot-rexate MTX or MTX + anti-tumour necrosis factor agents (anti-TNF) and in 105 healthy controls (HC). The primary outcome assessed was remission (DAS28 &lt; 2.6). The pilot analysis was performed on frozen PBMC obtained from 38 RA patients and 35 HC. These results were validated using fresh blood samples on a cohort of 70 RA patients and 70 HC. Results In the pilot study, T-cell subset analysis in early RA confirmed immune dysregulation compared to HC with reduced frequency of naïve CD4+ T-cells and Treg and increased IRC (all p &lt; 0.001) compared to HC. Naive T-cell above median was associated with remission (p = 0.001). In the validation study, 50 patients were treated with MTX and showed the same relationship with naïve cell frequency above median being associated with remission (p = 0.011). Individual analysis on each patient’s naïve cell frequency deviation from expected (using 70 HC) demonstrated that “normal” naïve cell frequency (observed in 30 patients) was associated with remission whereas reduced naïve cell frequency was more frequently observed in patients with poor response to MTX (p = 0.03). Patients with poor immunological status were not prevented to achieve remission when treated with MTX + anti-TNF (n = 20 including 10 patients with normal and 10 with reduced naïve cells) raising the rate of remission from 20% in the MTX group (n = 4 of the 20 patients with reduced naïve cells at baseline) to 60% in the MTX + anti-TNF group (n = 6 of the 10 patients). Conclusions These data show that baseline naïve T-cell subset analysis has a value in predicting early RA MTX treatment outcome. 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Parmar, Rekha ; El-Sherbiny, Yasser ; El Jawhari, Jehan ; Emery, Paul ; Ponchel, Frederique</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b2683-9d04bcfde4e2164f5bf30102d8d3928a133697f84429408c082d0df4132ecfe93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Burska, Agata</creatorcontrib><creatorcontrib>Parmar, Rekha</creatorcontrib><creatorcontrib>El-Sherbiny, Yasser</creatorcontrib><creatorcontrib>El Jawhari, Jehan</creatorcontrib><creatorcontrib>Emery, Paul</creatorcontrib><creatorcontrib>Ponchel, Frederique</creatorcontrib><collection>Istex</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><jtitle>Annals of the rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Burska, Agata</au><au>Parmar, Rekha</au><au>El-Sherbiny, Yasser</au><au>El Jawhari, Jehan</au><au>Emery, Paul</au><au>Ponchel, Frederique</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A3.3 An Immunological Window of Opportunity Defines the Ability of Early RA Patient to Achieve Remission with First Anti-Rheumatic Treatment</atitle><jtitle>Annals of the rheumatic diseases</jtitle><addtitle>Ann Rheum Dis</addtitle><date>2013-03</date><risdate>2013</risdate><volume>72</volume><issue>Suppl 1</issue><spage>A14</spage><pages>A14-</pages><issn>0003-4967</issn><eissn>1468-2060</eissn><coden>ARDIAO</coden><abstract>Background and Objectives The therapeutic goal for patients with rheumatoid arthritis (RA) is clinical remission. This is best achieved by early diagnosis followed by appropriate therapeutic intervention. RA is associated with dys-regulation of T-cell subsets early in the disease with naïve cells and regulatory T-cell losses and acquisition of abnormal subset in realtion with inflammation (IRC). Our aim was to test the hypothesis that T-cell subset quantification can predict the achievement of clinical remission in patients with early RA. Materials and Methods T-cell subsets (naive, Treg and IRC) were quantified using flow cytometry in 108 DMARDs-naïve, early RA patients (&lt;24 months) symptom duration commencing methot-rexate MTX or MTX + anti-tumour necrosis factor agents (anti-TNF) and in 105 healthy controls (HC). The primary outcome assessed was remission (DAS28 &lt; 2.6). The pilot analysis was performed on frozen PBMC obtained from 38 RA patients and 35 HC. These results were validated using fresh blood samples on a cohort of 70 RA patients and 70 HC. Results In the pilot study, T-cell subset analysis in early RA confirmed immune dysregulation compared to HC with reduced frequency of naïve CD4+ T-cells and Treg and increased IRC (all p &lt; 0.001) compared to HC. Naive T-cell above median was associated with remission (p = 0.001). In the validation study, 50 patients were treated with MTX and showed the same relationship with naïve cell frequency above median being associated with remission (p = 0.011). Individual analysis on each patient’s naïve cell frequency deviation from expected (using 70 HC) demonstrated that “normal” naïve cell frequency (observed in 30 patients) was associated with remission whereas reduced naïve cell frequency was more frequently observed in patients with poor response to MTX (p = 0.03). Patients with poor immunological status were not prevented to achieve remission when treated with MTX + anti-TNF (n = 20 including 10 patients with normal and 10 with reduced naïve cells) raising the rate of remission from 20% in the MTX group (n = 4 of the 20 patients with reduced naïve cells at baseline) to 60% in the MTX + anti-TNF group (n = 6 of the 10 patients). Conclusions These data show that baseline naïve T-cell subset analysis has a value in predicting early RA MTX treatment outcome. Immunological analysis could be used in conjunction with clinical/serological features to predict response to MTX and select the most appropriate therapy at disease presentation.</abstract><cop>Kidlington</cop><pub>BMJ Publishing Group Ltd and European League Against Rheumatism</pub><doi>10.1136/annrheumdis-2013-203216.3</doi><oa>free_for_read</oa></addata></record>
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title A3.3 An Immunological Window of Opportunity Defines the Ability of Early RA Patient to Achieve Remission with First Anti-Rheumatic Treatment
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