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Published on: December 9, 2015
Exosomal pHERV-W ENV as a dynamic biomarker for relapse prediction and prognosis in multiple sclerosis
Esber S Saba1, May F Mrad1,2, Layane Nakib1,2
1Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Background:
Emerging evidence implicates the envelope protein of human endogenous retrovirus type W (pHERV-W ENV) in the pathogenesis of multiple sclerosis (MS); however, its clinical utility as a biomarker remains incompletely defined. In this study, we demonstrate that pHERV-W ENV is enriched on serum-derived exosomes in patients with relapsing-remitting MS (RRMS), where it reflects both current disease activity and future risk.
Methods:
Exosomal pHERV-W ENV levels were profiled across three cohorts: (1) a cross-sectional cohort including healthy controls, stable MS patients, and patients with active disease; (2) a longitudinal RRMS cohort with samples collected before, during, and after episodes of disease activity; and (3) a retrospective longitudinal cohort of newly diagnosed RRMS patients with three years of follow-up.
Results:
We observed an increase in exosomal pHERV-W ENV expression during active disease, followed by a decline at follow-up. Levels of pHERV-W ENV expression during active disease positively correlated with Epstein-Barr virus (EBV)-derived latent membrane protein 2 A (LMP2A) expression, supporting an association between endogenous retroviral expression and EBV activity. Flow cytometric profiling of immune cell subsets identified monocytes and B cells as the predominant sources of circulating pHERV-W ENV. Longitudinal profiling further revealed coordinated immune and vascular activation during active disease, including a significant positive correlation between exosomal pHERV-W ENV and the costimulatory molecule CD40. Notably, high baseline levels of exosomal pHERV-W ENV were associated with greater total disease activity events, defined as the sum of clinical relapses and MRI activity (new/enlarging T2 or gadolinium-enhancing (Gd+) lesions) over three years, as well as with accelerated loss of "No Evidence of Disease Activity" (NEDA) status over time.
Conclusion:
These findings suggest that exosomal pHERV-W ENV expression may serve as a dynamic, non-invasive biomarker of disease activity with prognostic value in MS.
