Immune response against Epstein-Barr virus as an etiologic factor and therapeutic target for multiple sclerosis

Introduction . The etiology of multiple sclerosis (MS) remains unknown. According to the current consensus, susceptibility to MS is due to an elaborate interaction between genetic predisposition and multifactorial environmental factors, including vitamin D deficiency, smoking, inflammatory diet, psychoemotional stress, and infections. With regard to the infectious component, for decades, MS has been associated with a prior infection with the Epstein-Barr virus (EBV). However, it remains unclear why only a limited proportion of the numerous EBV-infected population develop MS. Objective. To discuss the factors of interaction between the immune system and EBV that predispose to the development of MS, as well as to analyze the possibilities of their use as therapeutic targets for the prevention and treatment of MS. Discussion . The results of a recent large epidemiologic study have provided new evidence for the association between EBV and MS. It has also been shown that cross-reacting antibodies to myelin sheath antigens can be detected in the blood of patients with EBV. However, most patients with EBV do not develop MS. This is probably due to the elimination of autoreactive cells. Natural killer (NK) cells play a particularly important role in this process. In MS, NK-mediated elimination of autoreactive B cells may be impaired. In this regard, an add-on therapy of MS aimed at controlling EBV-induced autoimmune responses appears promising. Conclusions . Reduced cytotoxic activity of NK cells against cells that show cross-reactivity to EBV antigens and components of the myelin sheath is among the factors of interaction of the immune system with EBV that contribute to MS development. As an add-on therapy for MS, it may be reasonable to use agents that reduce the presence of EBV in the organism and have a favorable safety profile (e.g., curcumin and quercetin). The search for agents that can improve immunological control of autoreactive cells is also promising. Such agents may include compounds that are capable of enhancing the activity of NK cells, for instance, urolithin A, curcumin, and alloferon.