Multiple sclerosis research has long grappled with a frustrating paradox: genetic risk explains only a fraction of who develops the disease, yet environmental triggers have remained poorly characterized. A comprehensive review in Biomolecules reframes MS as a condition where infectious exposures — both harmful and potentially protective — may be among the most consequential modulators of disease onset and progression, with implications for how next-generation therapies are designed.
The review centers on two mechanistic poles. On the pathogenic side, Epstein-Barr virus (EBV) is positioned as a particularly compelling MS trigger, operating through antibody-mediated molecular mimicry in which immune responses directed at viral antigens cross-react with central nervous system proteins — most notably GlialCAM — driving demyelination and neuroinflammation. B-cell dysregulation is identified as a central amplifying mechanism, linking EBV's well-known tropism for B lymphocytes to the loss of immunological tolerance characteristic of MS. On the opposing end, helminth infections and select protozoa are reviewed for their capacity to skew immune polarization toward regulatory and tolerogenic states, suppressing the Th1/Th17 pathogenic inflammation implicated in MS lesion formation.
This bidirectional framing is analytically valuable. The EBV-MS link has accumulated substantial epidemiological and molecular weight since the landmark 2022 Leibovitch and Bhatt military cohort study, making the mechanistic granularity offered here a useful synthesis. However, this is a narrative review, not a meta-analysis or clinical trial — causal hierarchies remain inferential. The helminth immunomodulation angle is especially intriguing from a longevity and neuroinflammation standpoint, as the hygiene hypothesis has long suggested that reduced parasitic exposure in industrialized populations may inadvertently heighten autoimmune risk. Whether deliberately harnessing parasite-derived immunoregulatory molecules could translate into viable MS therapeutics remains speculative but scientifically grounded. This review is best classified as confirmatory and synthesizing — it consolidates an emerging consensus rather than breaking new empirical ground.