Myelin Oligodendrocyte Glycoprotein: Deciphering a Target in Inflammatory Demyelinating Diseases

Abstract

Myelin oligodendrocyte glycoprotein (MOG), a member of the immunoglobulin (Ig) superfamily, is a myelin protein solely expressed at the outermost surface of myelin sheaths and oligodendrocyte membranes. This makes MOG a potential target of cellular and humoral immune responses in inflammatory demyelinating diseases. Due to its late postnatal developmental expression, MOG is an important marker for oligodendrocyte maturation. Discovered about 30 years ago, it is one of the best-studied autoantigens for experimental autoimmune models for multiple sclerosis (MS). Human studies, however, have yielded controversial results on the role of MOG, especially MOG antibodies (Abs), as a biomarker in MS. But with improved detection methods using different expression systems to detect Abs in patients’ samples, this is meanwhile no longer the case. Using cell-based assays with recombinant full-length, conformationally intact MOG, several recent studies have revealed that MOG Abs can be found in a subset of predominantly pediatric patients with acute disseminated encephalomyelitis (ADEM), aquaporin-4 (AQP4) seronegative neuromyelitis optica spectrum disorders (NMOSD), monophasic or recurrent isolated optic neuritis (ON), or transverse myelitis, in atypical MS and in N-methyl-d-aspartate receptor-encephalitis with overlapping demyelinating syndromes. Whereas MOG Abs are only transiently observed in monophasic diseases such as ADEM and their decline is associated with a favorable outcome, they are persistent in multiphasic ADEM, NMOSD, recurrent ON, or myelitis. Due to distinct clinical features within these diseases it is controversially disputed to classify MOG Ab-positive cases as a new disease entity. Neuropathologically, the presence of MOG Abs is characterized by MS-typical demyelination and oligodendrocyte pathology associated with Abs and complement. However, it remains unclear whether MOG Abs are a mere inflammatory bystander effect or truly pathogenetic. This article provides deeper insight into recent developments, the clinical relevance of MOG Abs and their role in the immunpathogenesis of inflammatory demyelinating disorders.

Calnexin is necessary for T cell transmigration into the central nervous system

“…Next, we asked whether calnexin deficiency impacted the development and function of the peripheral immune system and, hence, resistance of the calnexin-deficient mice to EAE induction. MS is an autoimmune disease in which antibodies and T cells targeting myelin antigens are present in the blood (21). The induction of EAE by immunization of mice with MOG leads to the appearance of anti-MOG antibodies and encephalogenic T cells in blood from immunized mice upon onset of the disease (22).…”

Nontarget metabolomics profiling of neuromyelitis optica spectrum disorder

“…(a) PCA score of group A (including A1 and A2) and group B. The abscissa PC (Wingerchuk et al, ) and the ordinate PC (Peschl et al, ) represent the scores of the first and second ranked principal components, and the scatter color and shape represent experimental groups of the samples. R 2 X (cum) = 0.553, representing the cumulative interpretation of X variables in the model.…”

“…The activation of the complement system and release of inflammatory mediators directly leads to the apoptosis of astrocytes and oligodendrocytes. Ultimately these internal changes cause demyelination and neurological deficits (Peschl, Bradl, Hoftberger, Berger, & Reindl, ; Wingerchuk, Lennon, Lucchinetti, Pittock, & Weinshenker, ). 10–25% of patients are negative for AQP‐4 antibody, however, and their clinical manifestations and therapeutic effects are different from those of antibody‐positive patients (Hinson, Lennon, & Pittock, ).…”

Respiratory virus-induced heterologous immunity

“…TCR cross-reactivity between MBP/MOG-derived and respiratory virus-derived epitopes has been shown for coronavirus [104], adenovirus [29] and influenza A virus HA epitopes ( [29,50]; Table 2). Anti-MOG antibodies, which are frequently found in ADEM [103], might have a pathogenic role, since they induce demyelinating disease in EAE animal models [105].…”