Targeting Antigen-Presenting Cells in Multiple Sclerosis Treatment

Abstract

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.

Unraveling the Immunopathogenesis of Multiple Sclerosis: The Dynamic Dance of Plasmablasts and Pathogenic T Cells

“…It is known that when the positions and positive or negative charge states of some amino acid residues match a certain pattern, they are recognized as target antigens. In addition, to activate the Th response, at the same time as receiving an appropriate antigen presentation from APC, it is essential that co-stimulatory signals enter through ligands for the co-stimulatory molecule CD28 present on the Th cell side [170]. Attempts have been made to paralyze or modify the function of MBP-reactive T cells to render them harmless.…”

Fuzzy Logic System for Classifying Multiple Sclerosis Patients as High, Medium, or Low Responders to Interferon-Beta

“…Treatment of MS can be divided into treatment of MS symptoms, treatment of MS relapse, and treatment modifying disease progression. The main target of MS treatment is delaying the disease progression [9]. Interferon-beta (IFN-β) is one of the most widely prescribed disease-modifying therapies for RRMS patients.…”