Glycoproteins as targets of autoantibodies in CNS inflammation: MOG and more

B cells and antibodies constitute an important element in different inflammatory diseases of the central nervous system (CNS). Autoantibodies can serve as a biomarker to identify disease subgroups and may in addition contribute to the pathogenic process. One candidate autoantigen for multiple sclerosis (MS) is myelin oligodendrocyte glycoprotein (MOG). MOG is localized at the outermost surface of myelin in the CNS and has been the focus of extensive research for more than 30 years. Its role as an important autoantigen for T cells and as a target of demyelinating autoantibodies has been established in several variants of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The literature regarding antibodies to MOG in MS patients is confusing and contradictory. Recent studies, however, have described high levels of antibodies to conformationally correct MOG in pediatric acquired demyelination, both acute disseminated encephalomyelitis (ADEM) and MS. In adult MS, such antibodies are rarely found and then only at low levels. In this review, we summarize key findings from animal models and patient studies, discuss challenges in detecting anti-MOG antibodies in patients and present recent approaches to identifying new autoantigens in MS

Autoimmunity in the brain: The pathogenesis insight from cell biology

The aim of the study is to explore the relationship between leakage of the blood-brain barrier and inflammation, the reason why demyelination occurs - seemingly in the absence of an antigen-specific immune response that requires explanation if a coherent account of an inflammatory-mediated demyelination is to be achieved. In this study the cellular biology of the glial cells important for the synthesis and maintenance of central nervous system (CNS) myelin and their inter-relations with other environmental cells (neuronal, microglial, olygodendroglial, astrocytes, endothelial, epithelial, T lymphocytes, B lymphocytes, monocytes, and macrophages) and with the compound of the extracellular matrix (ECM) during the development of an autoimmune inflammatory and demyelinating processes in the brain was analyzed. Upon activation in the peripheral tissue, immune cells reach their target organ via bloodstream and interacting with blood vessels wall components in the absence of exogenous stimulus mount an attack against the local milleu, which is the starting point of a pathogenic inflammatory reaction. Each of these contacts may trigger profuse secretion of cytokines, chemokines, and other soluble inflammatory mediators, which in the CNS by activating of local glial cells and by attracting and stimulating blood-borne monocyte/macrophages can act directly on neural cells and will cause their demyelination