Multiple sclerosis is characterised by the chronic inflammatory destruction of myelinated axons in the central nervous system. Several ideas have been put foward to clarify the roles of the peripheral immune system and neurodegenerative events in such destruction. Yet, none of the resulting models appears to be consistent with all the experimental evidence. They also do not answer the question why MS is exclusively seen in humans, how Epstein-Barr virus contributes to its development but does not immediately trigger it, and why optic neuritis is such a frequent early manifestation in MS. Here we describe a scenario for the development of MS that unifies existing experimental evidence as well as answer the above questions. We propose that all manifestions of MS are caused by a series of unfortunate events that usually unfold over a longer period of time after a primary EBV infection and involves periodic weakening of the blood-brain barrier, antibody-mediated CNS disturbances, accumulation of the oligodendrocyte stress protein αB-crystallin and self-sustaining inflammatory damage.
van Noort JM, Baker D, Kipp M, Amor S. The pathogenesis of multiple sclerosis: a series of unfortunate events. Clin Exp Immunol. 2023 Jul 6:uxad075. doi: 10.1093/cei/uxad075. Epub ahead of print. PMID: 37410892.
