Mechanistic biology linking traumatic brain injury to multiple sclerosis susceptibility.

Multiple sclerosis (MS) is a major, immune-mediated, demyelinating disease and the major cause of non-traumatic disability in young adults. Susceptibility to disease is controlled by a variety of interacting features that include genetic and notably environmental factors. One of these risk factors appears to be the occurrence of traumatic brain injury. In a follow-on to previous analysis of head injury-induced risk factors for MS, analysis of Swedish Registry data of MS and matched controls demonstrates enhanced susceptibility to MS, notably when stratified for the presence of HLA-DRB1*15.01, absence of HLA-A*02.01 and occurrence of smoking, which are known risk factors, the risk of MS increases to OR 65.4 (95% CI 8.35 to 512). This can be mechanistically supported by a number of routes whereby brain injury can lead to expression of autoantigenic targets, or damage-related release of neuroantigens that could generate a novel autoantigenic response in draining lymph nodes following glymphatic/meningeal lymphatic drainage. These may be different from other mechanisms that are relevant to susceptibility due to human leucocyte antigen expression and smoking.