Hypothesis: Multiple sclerosis is caused by three-hits, strictly in order, in genetically susceptible persons

Multiple Sclerosis and Related Disorders
Patrick K A KearnsJohn Paul Leach

Abstract

Multiple Sclerosis is a chronic, progressive and debilitating neurological disease which, despite extensive study for over 100 years, remains of enigmatic aetiology. Drawn from the epidemiological evidence, there exists a consensus that there are environmental (possibly infectious) factors that contribute to disease pathogenesis that have not yet been fully elucidated. Here we propose a three-tiered hypothesis: 1) a clinic-epidemiological model of multiple sclerosis as a rare late complication of two sequential infections (with the temporal sequence of infections being important); 2) a proposal that the first event is helminthic infection with Enterobius Vermicularis, and the second is Epstein Barr Virus infection; and 3) a proposal for a testable biological mechanism, involving T-Cell exhaustion for Epstein-Barr Virus protein LMP2A. We believe that this model satisfies some of the as-yet unexplained features of multiple sclerosis epidemiology, is consistent with the clinical and neuropathological features of the disease and is potentially testable by experiment. This model may be generalizable to other autoimmune diseases.

Citations

Mar 14, 2019·F1000Research·Aaron GregsonDavid L Selwood
Nov 29, 2020·Glia·Sofia Pereira das NevesFernanda Marques
Jan 5, 2021·Frontiers in Immunology·Gunnar HouenJette Lautrup Frederiksen
Jan 20, 2021·Multiple Sclerosis : Clinical and Laboratory Research·Maria L ElkjaerZsolt Illes

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