OPTIC NEUROMYELITIS DEVICIS: IMMUNOPATHOGENESIS AND RISK FACTORS (literature review and clinical case)

Background. Neuromyelitis optical spectrum disorders (NMOSD) or neuromyelitis optical (NMO) are inflammatory central nervous system disorders characterized by severe immune-mediated demyelination and axon destruction, with predominantly optic nerve and spinal cord damage. Previously, NMO and multiple sclerosis were thought to be a single disease with different phenotypes and expression. However, the results of studies in recent decades have revealed differences between these diseases in terms of pathogenesis, clinical features, neuroimaging findings, biomarkers, and treatment response. Aim: to summarize the current views of scientists on the basis of studies on the mechanisms of immunopathogenesis of optic neuromyelitis, to identify differences in immunological markers from other demyelinating diseases of the central nervous system, to assess possible risk factors for the occurrence of Devick's disease. Materials and methods. A literature review was conducted using the medical search databases “PubMed”, “Web of Science”, “Scopus”, as well as the service “Google Scholar” and more than 30 articles describing clinical, immunological and genomic studies on the immunopathogenesis and risk factors for the occurrence of optic neuromyelitis of Davick were selected for analysis (focusing on studies over the past decade). A clinical case of this pathology was analyzed. Results. As a result of our review of current literature, it was confirmed that autoimmune processes play an important role in the pathogenesis of optic neuromyelitis. Protein aquaporin-4 (AQP4) was identified as a target antigen in optic neuromyelitis, to which self-reactive Ig (immunoglobulins) G are synthesized. After binding of AQP4-IgG, the complement-dependent cytotoxicity (CDC) pathway is initiated, leading to the formation of necrotic lesions through the activation of the membrane-attacking complement complex. Chemotoxins enhance the effects of CDC through cellular infiltration and cytokine production. After cellular infiltration, anti-AQP4 Ig interacts with natural killer (NK) cells and leads to antibody-dependent cellular cytotoxicity (ADCC), which results in astrocyte death. It has been proven that in addition to humoral immunity, cellular immunity, especially T helper 17 lymphocytes (Th-17), as well as proinflammatory interleukins (Il) - Il-6, Il-17, Il-21, Il-1β - play an important role in the pathogenesis of optic neuromyelitis. The Th-17 subtype enhances the production of antibodies in naive B cells, and the cytokines produced by these cells have a crucial impact on pathogenesis. Certain studies in the world suggest the following risk factors for the development of optic neuromyelitis: genetic predispositions, viral and bacterial infections (Helicobacter pylori, Clostridium perfringens), vitamin D hypovitaminosis, and oxidative stress. Conclusion. Studies of recent decades have shown that both the humoral (IgG) and cellular (Th17) immune systems are involved in the immunopathogenesis of Devick's disease. It has been shown that the risk factors for its occurrence include both genetic prerequisites and past viral and bacterial infections, vitamin D hypovitaminosis, and oxidative stress. It is noted that today it is important to develop targeted therapy using highly selective monoclonal antibodies.