Altered Immune Phenotypes and HLA-DQB1 Gene Variation in Multiple Sclerosis Patients Failing Interferon β Treatment.

Frontiers in Immunology
Priyanka Devi-MarulkarFrédérique Michel

Abstract

Interferon beta (IFNβ) has been prescribed as a first-line disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS) for nearly three decades. However, there is still a lack of treatment response markers that correlate with the clinical outcome of patients. To determine a combination of cellular and molecular blood signatures associated with the efficacy of IFNβ treatment using an integrated approach. The immune status of 40 RRMS patients, 15 of whom were untreated and 25 that received IFNβ1a treatment (15 responders, 10 non-responders), was investigated by phenotyping regulatory CD4+ T cells and naïve/memory T cell subsets, by measurement of circulating IFNα/β proteins with digital ELISA (Simoa) and analysis of ~600 immune related genes including 159 interferon-stimulated genes (ISGs) with the Nanostring technology. The potential impact of HLA class II gene variation in treatment responsiveness was investigated by genotyping HLA-DRB1, -DRB3,4,5, -DQA1, and -DQB1, using as a control population the Milieu Interieur cohort of 1,000 French healthy donors. Clinical responders and non-responders displayed similar plasma levels of IFNβ and similar ISG profiles. However, non-responders mainly differed from other subj...Continue Reading

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Software Mentioned

Nanostring
nSolver
nCounter
Qlucore Omics Explorer
geomean
gNorm
GraphPAD Prism

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