TY - JOUR
T1 - The pathogenesis of multiple sclerosis
T2 - a series of unfortunate events
AU - van Noort, Johannes M.
AU - Baker, David
AU - Kipp, Markus
AU - Amor, Sandra
PY - 2023/10/1
Y1 - 2023/10/1
N2 - Multiple sclerosis (MS) is characterized by the chronic inflammatory destruction of myelinated axons in the central nervous system. Several ideas have been put forward 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 of 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 answers the above questions. We propose that all manifestations 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 involve periodic weakening of the blood–brain barrier, antibody-mediated CNS disturbances, accumulation of the oligodendrocyte stress protein αB-crystallin and self-sustaining inflammatory damage.
AB - Multiple sclerosis (MS) is characterized by the chronic inflammatory destruction of myelinated axons in the central nervous system. Several ideas have been put forward 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 of 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 answers the above questions. We propose that all manifestations 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 involve periodic weakening of the blood–brain barrier, antibody-mediated CNS disturbances, accumulation of the oligodendrocyte stress protein αB-crystallin and self-sustaining inflammatory damage.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85179771179&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/37410892
U2 - 10.1093/cei/uxad075
DO - 10.1093/cei/uxad075
M3 - Review article
C2 - 37410892
SN - 0009-9104
VL - 214
SP - 1
EP - 17
JO - Clinical and experimental immunology
JF - Clinical and experimental immunology
IS - 1
ER -