Multi-centre validation of a flow cytometry method to identify optimal responders to interferon-beta in multiple sclerosis.


Journal

Clinica chimica acta; international journal of clinical chemistry
ISSN: 1873-3492
Titre abrégé: Clin Chim Acta
Pays: Netherlands
ID NLM: 1302422

Informations de publication

Date de publication:
Jan 2019
Historique:
received: 23 08 2018
revised: 23 10 2018
accepted: 03 11 2018
pubmed: 9 11 2018
medline: 2 3 2019
entrez: 9 11 2018
Statut: ppublish

Résumé

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.

Sections du résumé

BACKGROUND AND OBJECTIVES OBJECTIVE
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.
METHODS METHODS
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.
RESULTS RESULTS
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.
CONCLUSION CONCLUSIONS
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.

Identifiants

pubmed: 30408481
pii: S0009-8981(18)30580-1
doi: 10.1016/j.cca.2018.11.008
pii:
doi:

Substances chimiques

Interferon-beta 77238-31-4

Types de publication

Journal Article Validation Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

135-142

Informations de copyright

Copyright © 2018 Elsevier B.V. All rights reserved.

Auteurs

Noelia Villarrubia (N)

Immunology Dpt. and Biostatistic Unit, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Viejo km 9.100, 28034 Madrid, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: noelia.villarrubia@salud.madrid.org.

Eulalia Rodríguez-Martín (E)

Immunology Dpt. and Biostatistic Unit, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Viejo km 9.100, 28034 Madrid, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: eulalia.rodriguez@salud.madrid.org.

Elisenda Alari-Pahissa (E)

Immunology and Neurology Dpt., Universitat Pompeu Fabra, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Carrer del Dr. Aiguader 88, 08003 Barcelona, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: ealari@imim.es.

Larraitz Aragón (L)

Immunology and Neurology Dpt., Hospital Universitario de Donostia, Biodonostia, P° Dr. Beguiristain 107-111, 20014 San Sebastián, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: larraitz.aragonirusquieta@osakidetza.eus.

Tamara Castillo-Triviño (T)

Immunology and Neurology Dpt., Hospital Universitario de Donostia, Biodonostia, P° Dr. Beguiristain 107-111, 20014 San Sebastián, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: tamaracastillo.tri@gmail.co.

Herena Eixarch (H)

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Cemcat, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron, 119-129, 08035 Barcelona, Spain. Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: herena.eixarch@vhir.org.

Joana María Ferrer (JM)

Immunology and Neurology Dpt., Hospital Universitari Son Espases, Instituto de Investigación Sanitaria Illes Balears, IdISBa, Ctra. Valldemossa 79, Palma 07010, Spain.

José Enrique Martínez-Rodríguez (JE)

Immunology and Neurology Dpt., Universitat Pompeu Fabra, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Carrer del Dr. Aiguader 88, 08003 Barcelona, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: jmartinezr@parcdesalutmar.cat.

Margarita Massot (M)

Immunology and Neurology Dpt., Hospital Universitari Son Espases, Instituto de Investigación Sanitaria Illes Balears, IdISBa, Ctra. Valldemossa 79, Palma 07010, Spain. Electronic address: margaritam.massot@ssib.es.

María Jesús Pinto-Medel (MJ)

Clinical Management Unit of Neurosciences, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Plaza del Hospital Civil s/n., Málaga, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: mjpmedel@ibima.eu.

Álvaro Prada (Á)

Immunology and Neurology Dpt., Hospital Universitario de Donostia, Biodonostia, P° Dr. Beguiristain 107-111, 20014 San Sebastián, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: alvarojose.pradainurrategui@osakidetza.eu.

Breogán Rodríguez-Acevedo (B)

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Cemcat, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron, 119-129, 08035 Barcelona, Spain. Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: brodriguez@cem-cat.org.

Patricia Urbaneja (P)

Clinical Management Unit of Neurosciences, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Plaza del Hospital Civil s/n., Málaga, Spain; Red Española de Esclerosis Múltiple (REEM), Spain.

Francisco Gascón-Gimenez (F)

Neuroimmunology Unit, Hospital Clínic Universitari de València, Av. de Blasco Ibáñez 17, 46010 València, Spain; Red Española de Esclerosis Múltiple (REEM), Spain.

Guadalupe Herrera (G)

Flow Cytometry Unit, UCIM, INCLIVA-Universidad de Valencia, Avda Blasco Ibañez 13, 46010 València, Spain.

Rocío Hernández-Clares (R)

Immunology and Neurology Dpt., Hospital Universitario Virgen de la Arrixaca, Ctra. Madrid-Cartagena, s/n, 30120 El Palmar, Murcia, Spain.

María Gema Salgado (MG)

Immunology and Neurology Dpt., Hospital Universitario Virgen de la Arrixaca, Ctra. Madrid-Cartagena, s/n, 30120 El Palmar, Murcia, Spain.

Agustín Oterino (A)

Immunology and Neurology Dpt., IDIVAL, Hospital Universitario Marqués de Valdecilla, Avda. Valdecilla 25, 39008 Santander, Spain; Red Española de Esclerosis Múltiple (REEM), Spain.

David San Segundo (D)

Immunology and Neurology Dpt., IDIVAL, Hospital Universitario Marqués de Valdecilla, Avda. Valdecilla 25, 39008 Santander, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: david.sansegundo@scsalud.es.

Juan Pablo Cuello (JP)

Immunology and Neurology Dpt., Hospital General Universitario and Instituto de Investigación Sanitaria "Gregorio Marañón", C/ Dr Esquerdo 46, 28007 Madrid, Spain. Electronic address: juanpablo.cuello@salud.madrid.org.

Juana Gil-Herrera (J)

Immunology and Neurology Dpt., Hospital General Universitario and Instituto de Investigación Sanitaria "Gregorio Marañón", C/ Dr Esquerdo 46, 28007 Madrid, Spain. Electronic address: juana.gil@salud.madrid.org.

Carmen Cámara (C)

Immunology and Neurology Dpt., Hospital San Pedro de Alcántara, Avda. Pablo Naranjo s/n, 10003 Cáceres, Spain. Electronic address: ccamarah@salud.madrid.org.

Montserrat Gómez-Gutiérrez (M)

Immunology and Neurology Dpt., Hospital San Pedro de Alcántara, Avda. Pablo Naranjo s/n, 10003 Cáceres, Spain.

Eugenia Martínez-Hernández (E)

Immunology and Neurology Dpt., Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036 Barcelona, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: emmartinez@clinic.ub.es.

Virginia Meca-Lallana (V)

Immunology and Neurology Dpt., Instituto de Investigación Sanitaria La Princesa, IIS-IP, Demyelinating Diseases Unit, Hospital Universitario de La Princesa, C/ Diego de León 62, 28006 Madrid, Spain.

Esther Moga (E)

Immunology and Neurology Dpt., Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, C/ Sant Antoni Maria Claret 167, 08025 Barcelona, Ciberer, Madrid, Spain. Electronic address: mmoga@santpau.cat.

Cecilia Muñoz-Calleja (C)

Immunology and Neurology Dpt., Instituto de Investigación Sanitaria La Princesa, IIS-IP, Demyelinating Diseases Unit, Hospital Universitario de La Princesa, C/ Diego de León 62, 28006 Madrid, Spain. Electronic address: cmunozc@salud.madrid.org.

Luis Querol (L)

Immunology and Neurology Dpt., Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, C/ Sant Antoni Maria Claret 167, 08025 Barcelona, Ciberer, Madrid, Spain. Electronic address: lquerol@santpau.cat.

Silvia Presas-Rodríguez (S)

Immunology and Neurology Dpt., Multiple Sclerosis Unit, Hospital Universitario e Instituto de Investigación Germans Trias i Pujol, Campus Can Ruti, 08916 Badalona, Barcelona, Spain; Red Española de Esclerosis Múltiple (REEM), Spain.

Aina Teniente-Serra (A)

Immunology and Neurology Dpt., Multiple Sclerosis Unit, Hospital Universitario e Instituto de Investigación Germans Trias i Pujol, Campus Can Ruti, 08916 Badalona, Barcelona, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: ateniente.germanstrias@gencat.cat.

Alexandru Vlagea (A)

Immunology and Neurology Dpt., Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036 Barcelona, Spain. Electronic address: vlagea@clinic.cat.

Alfonso Muriel (A)

Immunology Dpt. and Biostatistic Unit, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Viejo km 9.100, 28034 Madrid, Spain. Electronic address: alfonso.muriel@hrc.es.

Ernesto Roldán (E)

Immunology Dpt. and Biostatistic Unit, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Viejo km 9.100, 28034 Madrid, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: ernesto.roldan@salud.madrid.org.

Luisa María Villar (LM)

Immunology Dpt. and Biostatistic Unit, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. de Colmenar Viejo km 9.100, 28034 Madrid, Spain; Red Española de Esclerosis Múltiple (REEM), Spain. Electronic address: luisamaria.villar@salud.madrid.org.

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Classifications MeSH