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J Neurol. 2018 Jan;265(1):24-31. doi: 10.1007/s00415-017-8625-6. Epub 2017 Oct 12.

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

Author information

1
Servicio de Inmunología, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. Colmenar km 9.100, 28034, Madrid, Spain.
2
Red Española de Esclerosis Múltiple (REEM), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerios de Economía y Competitividad, Madrid, Spain.
3
Servicio de Neurología, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
4
Servicio de Neurología, Hospital Clínico San Carlos, IdISSC, Madrid, Spain.
5
Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
6
Universitat Autònoma de Barcelona, Barcelona, Spain.
7
Servicio de Inmunología, Hospital Universitario Ramón y Cajal, IRYCIS, Ctra. Colmenar km 9.100, 28034, Madrid, Spain. luisamaria.villar@salud.madrid.org.
8
Red Española de Esclerosis Múltiple (REEM), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerios de Economía y Competitividad, Madrid, Spain. luisamaria.villar@salud.madrid.org.

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.

KEYWORDS:

Biomarkers; Demyelinating diseases; Lymphocytes; Multiple sclerosis

PMID:
29027004
DOI:
10.1007/s00415-017-8625-6
[Indexed for MEDLINE]

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