Pathophysiology of multiple sclerosis and influence of environmental factors

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease considered to be autoimmune; its distribution is global, but more incident geographically at high latitudes. However, its etiology is still unknown. With this in mind, the currently most accepted hypothesis is that it is the result of gene-environment interaction, with emphasis on 3 factors: Epstein-Barr virus (EBV) infection, vitamin D deficiency and smoking. The aim of this study was to identify hypotheses of interaction between the aforementioned environmental factors and the development of MS. This work consisted of a literary review in virtual research libraries PubMed and Google Scholar, based on the search for the keywords "multiple sclerosis", "environmental factors", "smoking", "Epstein Barr virus" and "vitamin D" during the months from October 2020 to February 2021, using articles published between the years 2010 and 2021 as a selection criterion, with 60 articles being selected. The results obtained suggest that the relationship between EBV and MS can be explained by two proposals: reaction against self-proteins and formation of self-reactive cells. EBV has tropism for B lymphocytes, making it possible to transform these into latent memory B cells. Its self-reactive presence in the central nervous system (CNS) can generate the formation of inflammatory costimulatory signals that would lead to brain damage and the process of demyelination. The second theory refers to damage to specific proteins of oligondethrocytes by pathological recognition of these by lymphoid cells previously stimulated by EBV. Vitamin D is an important immunoregulatory substance capable of maintaining the balance between T-CD4+ lymphocytes. For this reason, its deficiency has been studied in individuals with MS. Research has shown that individuals with this condition have lower serum levels of this vitamin, and the primary cause may be different: polymorphism of the vitamin D receptor, low incidence of sunlight and insufficient intake of vitamin D. MS and vitamin D, scientists are studying the possibility of using cholecalciferol supplementation as a form of treatment for this disease. With regard to smoking, some of the reactions caused by it in the body related to the pathogenesis of MS are: increased local or diffuse oxidative stress, which can lead to systemic inflammation; reduced immunity against antigens; decreased tissue oxygenation and nutrition and epigenetic alterations, such as histone modification and DNA methylation. The set of these reactions can lead to the activation of the inflammatory process, destruction of the blood-brain barrier, destruction of CNS cells, and degradation of myelin due to a possible process of cross-reaction with tobacco glycoprotein. Furthermore, studies indicate that EBV, smoking and vitamin D deficiency seem to interact together, increasing the risk of developing MS. Conclusion: Such environmental factors are related to the epigenetics of MS, and may interact concomitantly and aggravate the progression of the disease. However, the results of the studies carried out so far are controversial, sometimes due to sample inconsistency, sometimes due to the interference of external factors. The need for further research is consensual in order to obtain safer results.