Table 1_Double-stranded RNA antiviral signature in early multiple sclerosis.xlsx

IntroductionViruses, particularly Epstein–Barr virus (EBV), are strongly implicated in multiple sclerosis (MS) pathogenesis, yet reliable biomarkers of active viral replication remain limited. Double-stranded RNA (dsRNA) represents a hallmark of viral replication and may serve as a measurable indicator of viral infection.
MethodsWe developed a sandwich ELISA to quantify dsRNA levels in matched plasma and cerebrospinal fluid (CSF) samples from 70 treatment-naïve MS patients at first clinical onset and in plasma from 26 sex- and age-matched healthy controls. We additionally assessed plasma and CSF antiviral cytokine concentrations and designed an indirect ELISA to measure anti-dsRNA antibody levels using poly(I:C) as the target antigen.
ResultsPlasma dsRNA levels were significantly elevated in MS patients compared to controls and positively correlated with antiviral cytokines, including GM-CSF, IFN-λ1, IFN-λ2/3, IFN-γ, IFN-α2, and IL-12p70. CSF samples exhibited increased IP-10 and IL-8 levels, and the single patient with detectable CSF dsRNA showed among the highest concentrations of both cytokines. A subset of ten patients (14%) with serological evidence of atypical EBV reactivation (EBNA1 IgG+/IgM+) had higher plasma dsRNA and antiviral cytokine levels than the remaining patients. Anti-dsRNA IgM, but not IgG or IgA, correlated positively with plasma dsRNA in both MS patients and controls, yet anti-dsRNA IgM levels were significantly reduced in MS compared to controls.
DiscussionOur findings identify increased plasma viral dsRNA coupled with reduced anti-dsRNA IgM antibody levels as potential biomarkers for a subpopulation of early MS patients and indicate a dysregulated anti-viral immune response.