[Typical and atypical optic neuritis]. / Tipichnyi i atipichnyi opticheskii nevrit.

Optic neuritis (ON) is one of the most common neuro-ophthalmic causes of vision loss worldwide. Demyelinating ON can be idiopathic or be one of the symptoms of autoimmune demyelinating diseases of the central nervous system (CNS) such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Demographic, clinical and radiological signs of ON in these CNS diseases have differences. In this regard, typical and atypical ON are currently distinguished. Recognizing the clinical features that differentiate typical MS-associated ON from atypical ON in NMOSD and MOGAD is important for choosing the correct disease management and treatment strategy. This review summarizes the data from clinical, laboratory, instrumental methods of management used for the differential diagnosis of optic neuritis.

[Optic neuropathies as an interdisciplinary subject of research]. / Opticheskie neiropatii kak predmet mezhdistsiplinarnogo izucheniya.

Despite the wide range of clinical, instrumental and laboratory methods used in modern ophthalmology, the problem of diagnosing optic neuropathy and identifying its etiology remains relevant. A complex multidisciplinary approach involving various specialists is required in the differential diagnosis of immune-mediated optic neuritis, for example in multiple sclerosis, neuromyelitis optica spectrum disorder, and MOG-associated diseases. Of special interest is differential diagnosis of optic neuropathy in demyelinating diseases of the central nervous system, hereditary optic neuropathies and ischemic optic neuropathy. The article presents a summary of scientific and practical results of differential diagnosis of optic neuropathies with various etiologies. Timely diagnosis and early therapy start reduces the degree of disability in patients with optic neuropathies of different etiologies.

[Hereditary optic neuropathy associated with demyelinating diseases of the central nervous system]. / Nasledstvennaya opticheskaya neiropatiya v sochetanii s demieliniziruyushchimi zabolevaniyami tsentral'noi nervnoi sistemy.

Demyelinating optic neuritis and hereditary optic neuropathy (HON) take a leading place among the diseases, the leading clinical syndrome of which is bilateral optic neuropathy with a simultaneous or sequential significant decrease in visual acuity. Optic neuritis can occur at the onset or be one of the syndromes within multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOGAD). HON are a group of neurodegenerative diseases, among which the most common variants are Leber's hereditary optic neuropathy (LHON), associated with mitochondrial DNA (mtDNA) mutations, and autosomal recessive optic neuropathy (ARON), caused by nuclear DNA (nDNA) mutations in DNAJC30. There are phenotypes of LHON «plus¼, one of which is the association of HON and CNS demyelination in the same patient. In such cases, the diagnosis of each of these diseases causes significant difficulties, due to the fact that in some cases there are clinical and radiological coincidences between demyelinating and hereditary mitochondrial diseases.

[The role of regulatory T cells in the development of autoimmune process in multiple sclerosis].

In the maintenance of immunological tolerance important role belongs to the recently discovered population of regulatory T-cells CD4+CD25+FoxP3 +. These cells have potential in suppressing pathologic immune responses observed at various autoimmune diseases including multiple sclerosis. We have shown a reduction in the number and functional activity of T-reg in peripheral blood of patients with multiple sclerosis in the acute stage, the increase in their number during remission, duration of the relationship of the autoimmune process and the degree of disability of patients with the contents of T-reg. The possibility of using the grown ex vivo T-reg for the correction of immunopathological process in multiple sclerosis.

[Mechanisms of Neurodegeneration in Multiple Sclerosis]. / Mekhanizmy neirodegeneratsii pri rasseyannom skleroze.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, which results in the formation of primary demyelinating lesions in the white and gray matter, as well as diffuse axonal and neuronal damage. Although there has been substantial progress in drug research in relapsing-remitting MS, treatment of progressive forms of the disease, can be challenging. Diffuse and compartmentalized lymphocyte and macrophage infiltration of the CNS tissue inhibits the differentiation of myelinating mature oligodendrocytes, disrupting the process of remyelination. Chronic inflammation that occurs behind a closed blood-brain barrier (BBB) leads to microglia activation, which increases mitochondrial damage to axons and neurons, and therefore triggers chronic oxidative stress and histotoxic hypoxia. Thus, raising awareness about the mechanisms of neurodegeneration appears relevant. In the late stages of MS, it is caused by chronic neuroaxonal damage, disruption of the regenerative ability of the CNS, and to a great extent determines the disease outcome.

[Increased suppressor activity of transformed ex vivo regulatory T-cells in comparison with unstimulated cells of the same donor]. / Povyshennaia supressornaia aktivnost' transformirovannykh ex vivo reguliatornykh T-kletok v sravnenii s nestimulirovannymi kletkami togo zhe donora.

Regulatory T-cells CD4⁺CD25⁺FoxP3⁺CD127low (Tregs) play a key role in the maintenance of tolerance to auto antigens, inhibit function of effector T and B lymphocytes, and provide a balance between effector and regulatory arms of immunity. Patients with autoimmune diseases have decreased Treg numbers and impaired suppressive activity. Transformed ex vivo autologous Tregs could restore destroyed balance of the immune system. We developed a method for Treg precursor cell cultivation. Following the method, we were able to grown up 300-400 million of Tregs cells from 50 ml of peripheral blood during a week. Transformed ex vivo Tregs are 90-95% CD4⁺CD25⁺FoxP3⁺CD127low and have increased expression of transcription genes FoxP3 and Helios. Transformed ex vivo Tregs have increased demethylation of FoxP3 promoter and activated genes of proliferation markers Cycline B1, Ki67 and LGALS 1. Transformed ex vivo Tregs have increased suppressive activity and up to 80-90% these cells secrete cytokines TNFα и IFNγ. Our data suggest transformed ex vivo autologous Tregs have genetic, immunophenotypic and functional characteristics for regulatory T-cells and further can be used for adoptive immunotherapy autoimmune diseases and inhibition of transplantation immunity.

[Monoclonal antibody therapies for rapidly progressive and highly active multiple sclerosis in the era of the COVID-19 pandemic]. / Terapiya monoklonal'nymi antitelami bystroprogressiruyushchego i vysokoaktivnogo rasseyannogo skleroza v epokhu pandemii COVID-19.

As the COVID-19 pandemic continues, reducing the risk of infection for immunocompromised patients remains an important issue. Patients with aggressive multiple sclerosis (MS) require immunosuppressive therapy in order to control the overactive autoimmune response. Preliminary international and national trials demonstrate that older age, higher disability status and progressive MS are generally associated with a more severe clinical course of COVID-19. However, uncertainty remains about the effect of disease-modifying therapies on the COVID-19 clinical presentation. In this article, we pay special attention to monoclonal antibodies used for immune reconstitution therapy, which results in significant changes to the T-cell and/or B-cell repertoire. Based on the published data from registries in different countries, we attempted to estimate the benefits and risks of these therapies in a complicated epidemiological setting.

[Myelin oligodendrocyte glycoprotein immunoglobulin G-associated encephalomyelitis]. / Entsefalomielity, assotsiirovannye s antitelami k mielin-oligodendrotsitarnomu glikoproteinu.

The article discusses the role of myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) in demyelinating diseases of the central nervous system. Clinical phenotypes of demyelinating syndromes associated with MOG-IgG that are currently included into neuromyelitis optica spectrum disorders (NMOSD) are described. However, it has been shown that encephalomyelitis associated with MOG-IgG (MOG-EM) has certain clinical, radiological, immunological and histopathological features that make it possible to single out these syndromes into a separate nosological form. We provide International recommendations that establish indications for testing MOG-IgG using cell-based assay. We discuss epidemiological issues and classification challenges of the disease. Various approaches to treatment and prevention of relapses of MOG-EM are analyzed.

[The treatment by expanded ex vivo autologous regulatory T-cells CD4+CD25+FoxP3+CD127low restores the balance of immune system in patients with remitting-relapsing multiple sclerosis]. / Lechenie vyrashchennymi ex vivo autologichnymi regulyatornymi T-kletkami CD4+CD25+FOXP3+CD127low vosstanavlivaet balans immunnoi sistemy patsientov s remittiruyushchim rasseyannym sklerozom.

AIM: To assess clinical efficacy and safety of the autologous (own) regulatory T-cells (Tregs)CD4+CD25+Foxp3+CD127low isolated from the blood of patients with remitting-relapsing multiple sclerosis. Patients with autoimmune diseases have the decreased number of peripheral Tregs (pTreg) and impaired suppressive ability. In order to restore levels of pTreg, it is possible to isolate precursor cells, enter expanded ex vivo autologous Treg cells and introduce an expanded amount of autologous cells as Treg vaccine. MATERIAL AND METHODS: A method of ex vivo Tregs expansion by 30-40 times within 5-7 days has been developed. Expanded ex vivo Tregs are more than 90% CD4+CD25+Foxp3+CD127low and have high suppressor activity. Fourteen patients with remitting-relapsing multiple sclerosis were included in pilot studies.Ex vivoTregs were introduced subcutaneously in dosefrom 2.8 to 4.5 108 cell per injection. The duration of follow-up was 1 year. RESULTS AND CONCLUSION: The numbers of pTregs in the blood of these patients elevated by 1.5-2 times. No adverse-effects, a decrease of relapses and stabilization of disability index were observed. It has been suggested that ex vivo expanded Tregs can compensate the impaired function of pTregs and can be used for adoptive immunotherapyof multiple sclerosis.

[Clinical significance of T-regulatory cells in multiple sclerosis].

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that develops due to the activation of selfreactive T-cells specific for myelin components. Regulatory T-cells CD4+CD25+Foxp3+ (T-reg) play an important role in the autoimmunity control and inhibition of T-cells-mediated myelin destruction. The aim of the study was to determine a number of T-reg in the blood of patients in different stages of disease, to evaluate their functional activity and to obtain T-reg induced ex vivo. The phenotypic analysis revealed the 2-3 fold reduction of T-reg in the exacerbation phase of MS and the increase of their content in the remission while the level of T-reg in the donor's blood remained significantly higher. The inverse correlation between the degree of severity and duration of MS and the number of T-reg was found. The suppression function of T-reg of MS patients was substantially decreased in the exacerbation and remission stages. The induction of ex vivo T-reg allows to increase the number of these cells by 30-90 times during 6-8 days. The induced T-reg have phenotypic and functional characteristics of native T-reg. The adaptive cell treatment using induced T-reg may become an instrument for correction of immune dysfunction in MS.