Targeting Antigen-Presenting Cells in Multiple Sclerosis Treatment

Multiple sclerosis (MS) is common neurological disease of the central nervous system (CNS) affecting mostly young adults. Despite decades of studies, its etiology and pathogenesis are not fully unraveled and treatment is still insufficient. The vast majority of studies suggest that the immune system plays a major role in MS development. This is also supported by the effectiveness of currently available MS treatments that target immunocompetent cells. In this review, the role of antigen-presenting cells (APC) in MS development as well as the novel therapeutic options targeting those cells in MS are presented. It is known that in MS, peripheral self-antigen-specific immune cells are activated during antigen presentation process and they enter the CNS through the disrupted blood–brain barrier (BBB). Myelin-reactive CD4+ T-cells can be activated by dendritic cells, infiltrating macrophages, microglia cells, or B-cells, which all express MHC class II molecules. There are also suggestions that brain endothelial cells may act as non-professional APCs and present myelin-specific antigens with MHC class II. Similarly, astrocytes, the major glial cells in the CNS, were shown to act as non-professional APCs presenting myelin antigens to autoreactive T-cells. Several currently available MS drugs such as natalizumab, fingolimod, alemtuzumab, and ocrelizumab may modulate antigen presentation in MS. Another way to use this mechanism in MS treatment may be the usage of specific tolerogenic dendritic cells or the induction of tolerance to myelin antigens by peptide vaccines.

Results of Expert Council meeting on modern principles of treatment optimization in patients with relapsing-remitting multiple sclerosis using anti-CD20 monoclonal antibody

The article presents the results of the discussion of the use of anti-B-cell therapy in multiple sclerosis (MS). These cells play a significant role in immunoregulation in MS, not only by producing antibodies to myelin antigens after transformation into plasma cells, but also by presenting the antigen to T cells, producing activation cytokines, and forming laminar follicles. The article provides an expert consensus statement on different drugs of this class in the MS treatment. In addition, the possibilities of determining the disease prognosis for the initially correct treatment choice are highlighted. Undoubtedly, there is a need for confirmation of the MS diagnosis, possible stratification of patients into different risk groups, and evaluation of the response to therapy. Potential additional research methods included evoked potentials and optical coherence tomography, baseline vitamin D3 level as a prognostic marker of the disease course, neurofilament levels in serum and cerebrospinal fluid to confirm neuron damage. However, it takes much time to study, determine the methodology, reference values, and develop a single standard approach to identify and implement a biomarker, which should then be implemented in routine clinical practice.

Recent Advances in Antigen-Specific Immunotherapies for the Treatment of Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system and is considered to be the leading non-traumatic cause of neurological disability in young adults. Current treatments for MS comprise long-term immunosuppressant drugs and disease-modifying therapies (DMTs) designed to alter its progress with the enhanced risk of severe side effects. The Holy Grail for the treatment of MS is to specifically suppress the disease while at the same time allow the immune system to be functionally active against infectious diseases and malignancy. This could be achieved via the development of immunotherapies designed to specifically suppress immune responses to self-antigens (e.g., myelin antigens). The present study attempts to highlight the various antigen-specific immunotherapies developed so far for the treatment of multiple sclerosis (e.g., vaccination with myelin-derived peptides/proteins, plasmid DNA encoding myelin epitopes, tolerogenic dendritic cells pulsed with encephalitogenic epitopes of myelin proteins, attenuated autologous T cells specific for myelin antigens, T cell receptor peptides, carriers loaded/conjugated with myelin immunodominant peptides, etc.), focusing on the outcome of their recent preclinical and clinical evaluation, and to shed light on the mechanisms involved in the immunopathogenesis and treatment of multiple sclerosis.

Conventional DCs sample and present myelin antigens in the healthy CNS and allow parenchymal T cell entry to initiate neuroinflammation

The central nervous system (CNS) is under close surveillance by immune cells, which mediate tissue homeostasis, protection, and repair. Conversely, in neuroinflammation, dysregulated leukocyte invasion into the CNS leads to immunopathology and neurological disability. To invade the brain parenchyma, autoimmune encephalitogenic T helper (TH) cells must encounter their cognate antigens (Ags) presented via local Ag-presenting cells (APCs). The precise identity of the APC that samples, processes, and presents CNS-derived Ags to autoaggressive T cells is unknown. Here, we used a combination of high-dimensional single-cell mapping and conditional MHC class II ablation across all CNS APCs to systematically interrogate each population for its ability to reactivate encephalitogenic THcells in vivo. We found a population of conventional dendritic cells, but not border-associated macrophages or microglia, to be essential for licensing T cells to initiate neuroinflammation.