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Blood lymphocyte subsets identify optimal responders to IFN-beta in MS

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A Correction to this article was published on 24 November 2017

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Abstract

Response to interferon-beta (IFN-beta) treatment is heterogeneous in multiple sclerosis (MS). We aimed to search for biomarkers predicting no evidence of disease activity (NEDA) status upon IFN-beta treatment in MS. 119 patients with relapsing–remitting MS (RRMS) initiating IFN-beta treatment were included in the study, and followed prospectively for 2 years. Neutralizing antibodies (NAb) were explored in serum samples obtained after 6 and 12 months of IFN-beta treatment. Soluble cytokines and blood lymphocytes were studied in basal samples by ELISA and flow cytometry, respectively. 9% of patients developed NAb. These antibodies were more frequent in patients receiving IFN-beta 1b than in those treated subcutaneous (p = 0.008) or intramuscular (p < 0.0001) IFN-beta 1a. No patient showing NAb remained NEDA during follow-up. Basal immunological variables are also associated with patient response. Percentages below 3% of CD19 + CD5 + cells (AUC 0.74, CI 0.63–0.84; OR 10.68, CI 3.55–32.15, p < 0.0001; Likelihood ratio 4.28) or above 2.6% of CD8 + perforin + T cells (AUC 0.79, CI 0.63–0.96; OR 6.11, CI 2.0–18.6, p = 0.0009; Likelihood ratio 5.47) increased the probability of achieving NEDA status during treatment. Basal blood immune cell subsets contribute to identify MS patients with a high probability of showing an optimal response to IFN-beta.

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Change history

  • 24 November 2017

    The author claims that his name is incorrectly listed on PubMed. It seems that the first and last name has been mixed up.

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Acknowledgements

This work was supported by Grants PI15/00513, RD16/0015/0001, RD16/0015/0004 and RD16/0015/0013 from the Fondo para la Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain and FEDER.

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Author notes

  1. Raquel Alenda and Lucienne Costa-Frossard contributed equally to this work.

Authors and Affiliations

  1. Servicio de Inmunología, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. Colmenar km 9.100, 28034, Madrid, Spain

    Raquel Alenda, Eulalia Rodríguez-Martín, Noelia Villarrubia & Luisa M. Villar

  2. Servicio de Neurología, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain

    Lucienne Costa-Frossard, Susana Sainz de la Maza & José C. Álvarez-Cermeño

  3. Servicio de Neurología, Hospital Clínico San Carlos, IdISSC, Madrid, Spain

    Roberto Alvarez-Lafuente & María I. Domínguez-Mozo

  4. Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya, Vall d’Hebron Institut de Recerca, Hospital Universitari Vall d’Hebron, Barcelona, Spain

    Carmen Espejo, Jordi Río & Xavier Montalban

  5. Universitat Autònoma de Barcelona, Barcelona, Spain

    Carmen Espejo, Jordi Río & Xavier Montalban

  6. Red Española de Esclerosis Múltiple (REEM), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerios de Economía y Competitividad, Madrid, Spain

    Raquel Alenda, Lucienne Costa-Frossard, Roberto Alvarez-Lafuente, Carmen Espejo, Eulalia Rodríguez-Martín, Susana Sainz de la Maza, Noelia Villarrubia, Jordi Río, María I. Domínguez-Mozo, Xavier Montalban, José C. Álvarez-Cermeño & Luisa M. Villar

Authors
  1. Raquel Alenda
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  2. Lucienne Costa-Frossard
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  3. Roberto Alvarez-Lafuente
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  4. Carmen Espejo
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  5. Eulalia Rodríguez-Martín
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  6. Susana Sainz de la Maza
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  7. Noelia Villarrubia
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  8. Jordi Río
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  9. María I. Domínguez-Mozo
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  10. Xavier Montalban
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  11. José C. Álvarez-Cermeño
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  12. Luisa M. Villar
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Corresponding author

Correspondence to Luisa M. Villar.

Ethics declarations

Ethical statement

The study protocol was approved by the Ethics Committee of Hospital Universitario Ramón y Cajal (Madrid, Spain) and of Hospital Universitari Vall d’Hebron (Barcelona, Spain). The study was carried out according to the International Conference on Harmonization Guidelines for Good Clinical Practice and the Declaration of Helsinki.

Informed consent

Every patient provided written informed consent before entering the study.

Conflicts of interest

LMV, LCF, SSM, JCA-C, JR and XM received payment for lecturing or travel expenses or research Grants or consultancy from Merck-Serono, Biogen, Sanofi-Genzyme, Roche, Bayer and Novartis. The remaining authors declare no conflicts of interest.

Additional information

José C. Álvarez-Cermeño and Luisa M. Villar were principal co-investigators.

A correction to this article is available online at https://doi.org/10.1007/s00415-017-8679-5.

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Alenda, R., Costa-Frossard, L., Alvarez-Lafuente, R. et al. Blood lymphocyte subsets identify optimal responders to IFN-beta in MS. J Neurol 265, 24–31 (2018). https://doi.org/10.1007/s00415-017-8625-6

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  • DOI: https://doi.org/10.1007/s00415-017-8625-6

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