Multi-centre validation of a flow cytometry method to identify optimal responders to interferon-beta in multiple sclerosis
Percentages of blood CD19+CD5+ B cells and CD8+perforin+ T lymphocytes can predict response to Interferon (IFN)-beta treatment in relapsing-remitting multiple sclerosis (RRMS) patients. We aimed to standardize their detection in a multicenter study, prior to their implementation in clinical practice...
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| Veröffentlicht in: | Clinica chimica acta 2019-01, Vol.488, p.135-142 |
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| creator | Villarrubia, Noelia Rodríguez-Martín, Eulalia Alari-Pahissa, Elisenda Aragón, Larraitz Castillo-Triviño, Tamara Eixarch, Herena Ferrer, Joana María Martínez-Rodríguez, José Enrique Massot, Margarita Pinto-Medel, María Jesús Prada, Álvaro Rodríguez-Acevedo, Breogán Urbaneja, Patricia Gascón-Gimenez, Francisco Herrera, Guadalupe Hernández-Clares, Rocío Salgado, María Gema Oterino, Agustín San Segundo, David Cuello, Juan Pablo Gil-Herrera, Juana Cámara, Carmen Gómez-Gutiérrez, Montserrat Martínez-Hernández, Eugenia Meca-Lallana, Virginia Moga, Esther Muñoz-Calleja, Cecilia Querol, Luis Presas-Rodríguez, Silvia Teniente-Serra, Aina Vlagea, Alexandru Muriel, Alfonso Roldán, Ernesto Villar, Luisa María |
| description | Percentages of blood CD19+CD5+ B cells and CD8+perforin+ T lymphocytes can predict response to Interferon (IFN)-beta treatment in relapsing-remitting multiple sclerosis (RRMS) patients. We aimed to standardize their detection in a multicenter study, prior to their implementation in clinical practice.
Fourteen hospitals participated in the study. A reference centre was established for comparison studies. Peripheral blood cells of 105 untreated RRMS patients were studied. Every sample was analyzed in duplicate in the participating centre and in the reference one by flow cytometry. When needed, participating centres corrected fluorescence compensations and negative cut-off position following reference centre suggestions. Concordance between results obtained by participating centres and by reference one was evaluated by intraclass correlation coefficients (ICC) and Spearman correlation test. Centre performance was measured by using z-scores values.
After results review and corrective actions implementation, overall ICC was 0.86 (CI: 0.81–0.91) for CD19+CD5+ B cell and 0.89 (CI: 0.85–0.93) for CD8+ perforin+ T cell quantification; Spearman r was 0.92 (0.89–0.95; p |
| doi_str_mv | 10.1016/j.cca.2018.11.008 |
| format | Article |
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Fourteen hospitals participated in the study. A reference centre was established for comparison studies. Peripheral blood cells of 105 untreated RRMS patients were studied. Every sample was analyzed in duplicate in the participating centre and in the reference one by flow cytometry. When needed, participating centres corrected fluorescence compensations and negative cut-off position following reference centre suggestions. Concordance between results obtained by participating centres and by reference one was evaluated by intraclass correlation coefficients (ICC) and Spearman correlation test. Centre performance was measured by using z-scores values.
After results review and corrective actions implementation, overall ICC was 0.86 (CI: 0.81–0.91) for CD19+CD5+ B cell and 0.89 (CI: 0.85–0.93) for CD8+ perforin+ T cell quantification; Spearman r was 0.92 (0.89–0.95; p <0.0001) and 0.92 (0.88–0.95; p <0.0001) respectively. All centres obtained z-scores≤0.5 for both biomarkers.
Homogenous percentages of CD19+CD5+ B cells and CD8 perforin+ T lymphocytes can be obtained if suitable compensation values and negative cut-off are pre-established.
•Multi-centre validation of two flow cytometry biomarkers in multiple sclerosis.•This study shows the need of pre-established compensation values and axis settings.•This strategy gives highly concordant results for both biomarkers.•The high concordance shows that both biomarkers can be used in clinical practice.</description><identifier>ISSN: 0009-8981</identifier><identifier>EISSN: 1873-3492</identifier><identifier>DOI: 10.1016/j.cca.2018.11.008</identifier><identifier>PMID: 30408481</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Biomarkers ; Female ; Flow Cytometry ; Humans ; Immunology ; Interferon-beta - therapeutic use ; Male ; Middle Aged ; Multicenter Studies as Topic ; Multiple sclerosis ; Multiple Sclerosis - blood ; Multiple Sclerosis - drug therapy</subject><ispartof>Clinica chimica acta, 2019-01, Vol.488, p.135-142</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-e6d712057c01c26a675a258d18259315fefc0aa324e144e9d821b759bee0b1ba3</citedby><cites>FETCH-LOGICAL-c353t-e6d712057c01c26a675a258d18259315fefc0aa324e144e9d821b759bee0b1ba3</cites><orcidid>0000-0001-5745-9072 ; 0000-0002-9067-3668 ; 0000-0002-2114-8632</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0009898118305801$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30408481$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Villarrubia, Noelia</creatorcontrib><creatorcontrib>Rodríguez-Martín, Eulalia</creatorcontrib><creatorcontrib>Alari-Pahissa, Elisenda</creatorcontrib><creatorcontrib>Aragón, Larraitz</creatorcontrib><creatorcontrib>Castillo-Triviño, Tamara</creatorcontrib><creatorcontrib>Eixarch, Herena</creatorcontrib><creatorcontrib>Ferrer, Joana María</creatorcontrib><creatorcontrib>Martínez-Rodríguez, José Enrique</creatorcontrib><creatorcontrib>Massot, Margarita</creatorcontrib><creatorcontrib>Pinto-Medel, María Jesús</creatorcontrib><creatorcontrib>Prada, Álvaro</creatorcontrib><creatorcontrib>Rodríguez-Acevedo, Breogán</creatorcontrib><creatorcontrib>Urbaneja, Patricia</creatorcontrib><creatorcontrib>Gascón-Gimenez, Francisco</creatorcontrib><creatorcontrib>Herrera, Guadalupe</creatorcontrib><creatorcontrib>Hernández-Clares, Rocío</creatorcontrib><creatorcontrib>Salgado, María Gema</creatorcontrib><creatorcontrib>Oterino, Agustín</creatorcontrib><creatorcontrib>San Segundo, David</creatorcontrib><creatorcontrib>Cuello, Juan Pablo</creatorcontrib><creatorcontrib>Gil-Herrera, Juana</creatorcontrib><creatorcontrib>Cámara, Carmen</creatorcontrib><creatorcontrib>Gómez-Gutiérrez, Montserrat</creatorcontrib><creatorcontrib>Martínez-Hernández, Eugenia</creatorcontrib><creatorcontrib>Meca-Lallana, Virginia</creatorcontrib><creatorcontrib>Moga, Esther</creatorcontrib><creatorcontrib>Muñoz-Calleja, Cecilia</creatorcontrib><creatorcontrib>Querol, Luis</creatorcontrib><creatorcontrib>Presas-Rodríguez, Silvia</creatorcontrib><creatorcontrib>Teniente-Serra, Aina</creatorcontrib><creatorcontrib>Vlagea, Alexandru</creatorcontrib><creatorcontrib>Muriel, Alfonso</creatorcontrib><creatorcontrib>Roldán, Ernesto</creatorcontrib><creatorcontrib>Villar, Luisa María</creatorcontrib><title>Multi-centre validation of a flow cytometry method to identify optimal responders to interferon-beta in multiple sclerosis</title><title>Clinica chimica acta</title><addtitle>Clin Chim Acta</addtitle><description>Percentages of blood CD19+CD5+ B cells and CD8+perforin+ T lymphocytes can predict response to Interferon (IFN)-beta treatment in relapsing-remitting multiple sclerosis (RRMS) patients. We aimed to standardize their detection in a multicenter study, prior to their implementation in clinical practice.
Fourteen hospitals participated in the study. A reference centre was established for comparison studies. Peripheral blood cells of 105 untreated RRMS patients were studied. Every sample was analyzed in duplicate in the participating centre and in the reference one by flow cytometry. When needed, participating centres corrected fluorescence compensations and negative cut-off position following reference centre suggestions. Concordance between results obtained by participating centres and by reference one was evaluated by intraclass correlation coefficients (ICC) and Spearman correlation test. Centre performance was measured by using z-scores values.
After results review and corrective actions implementation, overall ICC was 0.86 (CI: 0.81–0.91) for CD19+CD5+ B cell and 0.89 (CI: 0.85–0.93) for CD8+ perforin+ T cell quantification; Spearman r was 0.92 (0.89–0.95; p <0.0001) and 0.92 (0.88–0.95; p <0.0001) respectively. All centres obtained z-scores≤0.5 for both biomarkers.
Homogenous percentages of CD19+CD5+ B cells and CD8 perforin+ T lymphocytes can be obtained if suitable compensation values and negative cut-off are pre-established.
•Multi-centre validation of two flow cytometry biomarkers in multiple sclerosis.•This study shows the need of pre-established compensation values and axis settings.•This strategy gives highly concordant results for both biomarkers.•The high concordance shows that both biomarkers can be used in clinical practice.</description><subject>Adult</subject><subject>Biomarkers</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Immunology</subject><subject>Interferon-beta - therapeutic use</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multicenter Studies as Topic</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis - blood</subject><subject>Multiple Sclerosis - drug therapy</subject><issn>0009-8981</issn><issn>1873-3492</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9v3CAQxVGVqNmk_QC9VBxzscuA_2D1FEVJGylVL-0ZYRirrLBxgU20-fRhu0mOvQCjee8N8yPkE7AaGHRftrUxuuYMZA1QMybfkQ3IXlSiGfgJ2TDGhkoOEs7IeUrbUjasg_fkTJSHbCRsyNOPnc-uMrjkiPRBe2d1dmGhYaKaTj48UrPPYcYc97Scf4KlOVBni8FNexrW7GbtacS0hsViTP_aS8Y4YQxLNWLWpabzYc7qkSbjSyO59IGcTton_PhyX5Dftze_rr9X9z-_3V1f3VdGtCJX2NkeOGt7w8DwTnd9q3krLUjeDgLaCSfDtBa8QWgaHKzkMPbtMCKyEUYtLsjlMXeN4e8OU1azSwa91wuGXVIcBOeiHzpepHCUmvLDFHFSayzrxb0Cpg7I1VYV5OqAXAGogrx4Pr_E78YZ7ZvjlXERfD0KsCz54DCqZBwuBq2LaLKywf0n_hk5iZOf</recordid><startdate>201901</startdate><enddate>201901</enddate><creator>Villarrubia, Noelia</creator><creator>Rodríguez-Martín, Eulalia</creator><creator>Alari-Pahissa, Elisenda</creator><creator>Aragón, Larraitz</creator><creator>Castillo-Triviño, Tamara</creator><creator>Eixarch, Herena</creator><creator>Ferrer, Joana María</creator><creator>Martínez-Rodríguez, José Enrique</creator><creator>Massot, Margarita</creator><creator>Pinto-Medel, María Jesús</creator><creator>Prada, Álvaro</creator><creator>Rodríguez-Acevedo, Breogán</creator><creator>Urbaneja, Patricia</creator><creator>Gascón-Gimenez, Francisco</creator><creator>Herrera, Guadalupe</creator><creator>Hernández-Clares, Rocío</creator><creator>Salgado, María Gema</creator><creator>Oterino, Agustín</creator><creator>San Segundo, David</creator><creator>Cuello, Juan Pablo</creator><creator>Gil-Herrera, Juana</creator><creator>Cámara, Carmen</creator><creator>Gómez-Gutiérrez, Montserrat</creator><creator>Martínez-Hernández, Eugenia</creator><creator>Meca-Lallana, Virginia</creator><creator>Moga, Esther</creator><creator>Muñoz-Calleja, Cecilia</creator><creator>Querol, Luis</creator><creator>Presas-Rodríguez, Silvia</creator><creator>Teniente-Serra, Aina</creator><creator>Vlagea, Alexandru</creator><creator>Muriel, Alfonso</creator><creator>Roldán, Ernesto</creator><creator>Villar, Luisa María</creator><general>Elsevier B.V</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><orcidid>https://orcid.org/0000-0001-5745-9072</orcidid><orcidid>https://orcid.org/0000-0002-9067-3668</orcidid><orcidid>https://orcid.org/0000-0002-2114-8632</orcidid></search><sort><creationdate>201901</creationdate><title>Multi-centre validation of a flow cytometry method to identify optimal responders to interferon-beta in multiple sclerosis</title><author>Villarrubia, Noelia ; Rodríguez-Martín, Eulalia ; Alari-Pahissa, Elisenda ; Aragón, Larraitz ; Castillo-Triviño, Tamara ; Eixarch, Herena ; Ferrer, Joana María ; Martínez-Rodríguez, José Enrique ; Massot, Margarita ; Pinto-Medel, María Jesús ; Prada, Álvaro ; Rodríguez-Acevedo, Breogán ; Urbaneja, Patricia ; Gascón-Gimenez, Francisco ; Herrera, Guadalupe ; Hernández-Clares, Rocío ; Salgado, María Gema ; Oterino, Agustín ; San Segundo, David ; Cuello, Juan Pablo ; Gil-Herrera, Juana ; Cámara, Carmen ; Gómez-Gutiérrez, Montserrat ; Martínez-Hernández, Eugenia ; Meca-Lallana, Virginia ; Moga, Esther ; Muñoz-Calleja, Cecilia ; Querol, Luis ; Presas-Rodríguez, Silvia ; Teniente-Serra, Aina ; Vlagea, Alexandru ; Muriel, Alfonso ; Roldán, Ernesto ; Villar, Luisa María</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-e6d712057c01c26a675a258d18259315fefc0aa324e144e9d821b759bee0b1ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Biomarkers</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>Immunology</topic><topic>Interferon-beta - 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Academic</collection><jtitle>Clinica chimica acta</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Villarrubia, Noelia</au><au>Rodríguez-Martín, Eulalia</au><au>Alari-Pahissa, Elisenda</au><au>Aragón, Larraitz</au><au>Castillo-Triviño, Tamara</au><au>Eixarch, Herena</au><au>Ferrer, Joana María</au><au>Martínez-Rodríguez, José Enrique</au><au>Massot, Margarita</au><au>Pinto-Medel, María Jesús</au><au>Prada, Álvaro</au><au>Rodríguez-Acevedo, Breogán</au><au>Urbaneja, Patricia</au><au>Gascón-Gimenez, Francisco</au><au>Herrera, Guadalupe</au><au>Hernández-Clares, Rocío</au><au>Salgado, María Gema</au><au>Oterino, Agustín</au><au>San Segundo, David</au><au>Cuello, Juan Pablo</au><au>Gil-Herrera, Juana</au><au>Cámara, Carmen</au><au>Gómez-Gutiérrez, Montserrat</au><au>Martínez-Hernández, Eugenia</au><au>Meca-Lallana, Virginia</au><au>Moga, Esther</au><au>Muñoz-Calleja, Cecilia</au><au>Querol, Luis</au><au>Presas-Rodríguez, Silvia</au><au>Teniente-Serra, Aina</au><au>Vlagea, Alexandru</au><au>Muriel, Alfonso</au><au>Roldán, Ernesto</au><au>Villar, Luisa María</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multi-centre validation of a flow cytometry method to identify optimal responders to interferon-beta in multiple sclerosis</atitle><jtitle>Clinica chimica acta</jtitle><addtitle>Clin Chim Acta</addtitle><date>2019-01</date><risdate>2019</risdate><volume>488</volume><spage>135</spage><epage>142</epage><pages>135-142</pages><issn>0009-8981</issn><eissn>1873-3492</eissn><abstract>Percentages of blood CD19+CD5+ B cells and CD8+perforin+ T lymphocytes can predict response to Interferon (IFN)-beta treatment in relapsing-remitting multiple sclerosis (RRMS) patients. We aimed to standardize their detection in a multicenter study, prior to their implementation in clinical practice.
Fourteen hospitals participated in the study. A reference centre was established for comparison studies. Peripheral blood cells of 105 untreated RRMS patients were studied. Every sample was analyzed in duplicate in the participating centre and in the reference one by flow cytometry. When needed, participating centres corrected fluorescence compensations and negative cut-off position following reference centre suggestions. Concordance between results obtained by participating centres and by reference one was evaluated by intraclass correlation coefficients (ICC) and Spearman correlation test. Centre performance was measured by using z-scores values.
After results review and corrective actions implementation, overall ICC was 0.86 (CI: 0.81–0.91) for CD19+CD5+ B cell and 0.89 (CI: 0.85–0.93) for CD8+ perforin+ T cell quantification; Spearman r was 0.92 (0.89–0.95; p <0.0001) and 0.92 (0.88–0.95; p <0.0001) respectively. All centres obtained z-scores≤0.5 for both biomarkers.
Homogenous percentages of CD19+CD5+ B cells and CD8 perforin+ T lymphocytes can be obtained if suitable compensation values and negative cut-off are pre-established.
•Multi-centre validation of two flow cytometry biomarkers in multiple sclerosis.•This study shows the need of pre-established compensation values and axis settings.•This strategy gives highly concordant results for both biomarkers.•The high concordance shows that both biomarkers can be used in clinical practice.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>30408481</pmid><doi>10.1016/j.cca.2018.11.008</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-5745-9072</orcidid><orcidid>https://orcid.org/0000-0002-9067-3668</orcidid><orcidid>https://orcid.org/0000-0002-2114-8632</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-8981 |
| ispartof | Clinica chimica acta, 2019-01, Vol.488, p.135-142 |
| issn | 0009-8981 1873-3492 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2132237962 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult Biomarkers Female Flow Cytometry Humans Immunology Interferon-beta - therapeutic use Male Middle Aged Multicenter Studies as Topic Multiple sclerosis Multiple Sclerosis - blood Multiple Sclerosis - drug therapy |
| title | Multi-centre validation of a flow cytometry method to identify optimal responders to interferon-beta in multiple sclerosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T09%3A44%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Multi-centre%20validation%20of%20a%20flow%20cytometry%20method%20to%20identify%20optimal%20responders%20to%20interferon-beta%20in%20multiple%20sclerosis&rft.jtitle=Clinica%20chimica%20acta&rft.au=Villarrubia,%20Noelia&rft.date=2019-01&rft.volume=488&rft.spage=135&rft.epage=142&rft.pages=135-142&rft.issn=0009-8981&rft.eissn=1873-3492&rft_id=info:doi/10.1016/j.cca.2018.11.008&rft_dat=%3Cproquest_cross%3E2132237962%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2132237962&rft_id=info:pmid/30408481&rft_els_id=S0009898118305801&rfr_iscdi=true |