The initiation of multiple sclerosis: a new infectious hypothesis.
Both genetic and environmental factors cause multiple sclerosis (MS). Few genes have been identified, however, and environmental factors remain elusive. Some postulate an infectious cause, but no pathogens are reproducibly demonstrable in CNS lesions. I postulate that the CNS is not the infectious target in MS, but propose a two-hit infectious hypothesis focusing on nai;ve CD4 T-cells that initiate demyelination: (1) Various common viruses infect the thymus during childhood (first hit) and enhance nai;ve CD4 T-cell reactivity to CNS autoantigens; (2) Heterogeneous pathogens fully activate these T-cells during adulthood (second hit) to initiate myelin injury. The novel concept of thymic infection provides insight into the nature of some susceptibility genes, helps explain the high discordance rates in genetically susceptible individuals, and suggests it is futile to search for pathogens in MS lesions. Pathogen heterogeneity, i.e., the lack of a single infectious cause, implies there can be no simple therapies to prevent or treat MS.
Haegert
David G
DG
Memorial University of Newfoundland, St. John's, Newfoundland, Canada. david.haegert@muhc.mcgill.ca
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002490:Central Nervous System / Q000473:pathology; D004200:Diseases in Twins; D006801:Humans; D009103:Multiple Sclerosis / Q000209:etiology* / Q000235:genetics*; D013950:Thymus Gland / Q000473:pathology