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

Publication date: Available online 4 July 2018Source: Multiple Sclerosis and Related DisordersAuthor(s): Patrick K A Kearns, Helen A Casey, John Paul LeachAbstractMultiple 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.Graphical Abstract
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research