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

Expression of EAAT1 reflects a possible neuroprotective function of reactive astrocytes and activated microglia following human traumatic brain injury

Glutamate-mediated excitotoxicity is known to cause secondary brain damage following stroke and traumatic brain injury (TBI). However, clinical trials using NMDA antagonists failed. Thus, glial excitatory amino acid transporters (EAATs) might be a promising target for therapeutic intervention. Methods and Results. We examined expression of EAAT1 (GLAST) and EAAT2 (Glt-1) in 36 TBI cases by immunohistochemistry. Cortical expression of both EAATs decreased rapidly and widespread throughout the brain (in lesional, adjacent and remote areas) following TBI. In the white matter numbers of EAAT1+ parenchymal cells increased 39-fold within 24h (p<0.001) and remained markedly elevated till later stages in the lesion (90-fold, p<0.01) and in peri-lesional regions (86-fold, p<0.01). In contrast, EAAT2+ parenchymal cells and EAAT1+ or EAAT2+ perivascular cells did not increase significantly. Within the first days following TBI mainly activated microglia and thereafter mainly reactive astrocytes expressed EAAT1. Perivascular monocytes and foamy macrophages lacked EAAT1 immunoreactivity. We conclude that following TBI i) loss of cortical EAATs contributes to secondary brain damage, ii) glial EAAT1 expression reflects a potential neuroprotective function of microglia and astrocytes, iii) microglial EAAT1 expression is restricted to an early stage of activation, iv) blood-derived monocytes do not express EAAT1 and v) pharmacological modification of glial EAAT expression might further limit neuronal damage