Autoimmune neurologic diseases

B Cell Subsets as Potential Biomarkers for Fingolimod Treatment in Multiple Sclerosis (MS)

Friday, June 16
4:30 PM - 4:45 PM

Several S1P-receptor functional antagonists are being pursued for the treatment of MS, with fingolimod approved as first-in-class in 2010. While many patients become free of new brain lesions and clinical relapses (Stable), a proportion of patients continue to develop new disease activity (Active) in spite of ongoing treatment. In this study, we aimed to identify a potential predictive biomarker to distinguish such Active versus Stable patients in a prospectively followed cohort of 33 RRMS patients receiving clinically-indicated fingolimod treatment. Patients were ascertained as either Active (n=17) or Stable (n=16) based on whether they did, or did not, develop new T2 brain MRI lesions and/or clinical relapses over 2 years of treatment. High quality PBMC were collected pre- and post-fingolimod and interrogated in-batch using 18-colour flow cytometry panels to functionally immune-phenotype over 80 immune-cell subsets. As expected, circulating counts of all major lymphocyte populations decreased substantially on-treatment, in both groups. While counts of T cell, myeloid cell and NK cell subsets did not differ pre-fingolimod between the two groups, B cell counts were significantly higher in the Active group at baseline (p=0.0066), mainly reflecting increased numbers of mature (p=0.0061) but not transitional (p=0.6233) B cells. Among mature B cells, both pro- and anti-inflammatory cytokine-defined B cell subsets were increased in the Active group, suggesting a more general active phenotype of these B cells in patients destined to experience continued disease activity on-treatment. Our data identify mature B-cell counts as a potential predictive biomarker of fingolimod treatment-response in RRMS patients.

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Mathab Ghadiri

Montreal Neurological Institute, McGill University

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Ayman Rezk

Ph.D Candidate
Montreal Neurological Institute, McGill University

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Paul Giacomini

Montreal Neurological Institute, McGill University

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Jack Antel

Professor
McGill University, Montreal Neurological Institute

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Amit Bar-Or

Melissa and Paul Anderson President’s Distinguished Professor
University of Pennsylvania and McGill University

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B Cell Subsets as Potential Biomarkers for Fingolimod Treatment in Multiple Sclerosis (MS)



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