There is emerging evidence that the commensal microbiota has a role in the pathogenesis of multiple sclerosis (MS), a putative autoimmune disease of the CNS. Here, we compared the gut microbial composition of 34 monozygotic twin pairs discordant for MS. While there were no major differences in the overall microbial profiles, we found a significant increase in some taxa such as Akkermansia in untreated MS twins. Furthermore, most notably, when transplanted to a transgenic mouse model of spontaneous brain autoimmunity, MS twin-derived microbiota induced a significantly higher incidence of autoimmunity than the healthy twin-derived microbiota. The microbial profiles of the colonized mice showed a high intraindividual and remarkable temporal stability with several differences, including Sutterella, an organism shown to induce a protective immunoregulatory profile in vitro. Immune cells from mouse recipients of MS-twin samples produced less IL-10 than immune cells from mice colonized with healthy-twin samples. IL-10 may have a regulatory role in spontaneous CNS autoimmunity, as neutralization of the cytokine in mice colonized with healthy-twin fecal samples increased disease incidence. These findings provide evidence that MS-derived microbiota contain factors that precipitate an MS-like autoimmune disease in a transgenic mouse model. They hence encourage the detailed search for protective and pathogenic microbial components in human MS.

This study provides Class IV evidence that repeated doses of rituximab result in stabilization in most patients.

MOG-specific Abs affinity purified from patients with inflammatory demyelinating disease induce pathological changes in vivo upon cotransfer with myelin-reactive T cells, suggesting that these Abs are similarly pathogenic in patients. Ann Neurol 2018;84:315-328.

We present histological, MRI, and clinical features of an adult patient with relapsing encephalomyelitis and antibodies against myelin oligodendrocyte glycoprotein (MOG). Furthermore, we report molecular details of the recognized epitope that is specific for human MOG. A brain biopsy revealed multiple sclerosis (MS)-type II pathology. Some features overlapped with both MS and neuromyelitis optica spectrum disorders (NMOSD), whereas others were distinct from both MS and NMOSD. Immunoadsorption and rituximab induced clinical stabilization. This case contributes a new, so far missing link in the emerging spectrum of MOG-antibody-associated encephalomyelitis.

Objectives:To evaluate the presence of antibodies to conformation-intact myelin oligodendrocyte glycoprotein (MOG) in a subgroup of adult patients with clinically definite multiple sclerosis (MS) preselected for a specific clinical phenotype including severe spinal cord, optic nerve, and brainstem involvement.Methods:Antibodies to MOG were investigated using a cell-based assay in 3 groups of patients: 104 preselected patients with MS (group 1), 55 age- and sex-matched, otherwise unselected patients with MS (group 2), and in 22 brain-biopsied patients with demyelinating diseases of the CNS (n = 19 with MS), 4 of whom classified as MS type II (group 3). Recognized epitopes were identified with mutated variants of MOG.Results:Antibodies to MOG were found in about 5% (5/104) of preselected adult patients with MS. In contrast, in groups 2 and 3, none of the patients tested positive for MOG antibodies. Patients with MS with antibodies to MOG predominantly manifested with concomitant severe brainstem and spinal cord involvement and had a severe disease course with high relapse rates and failure to several disease-modifying therapies. Three of them had been treated with plasma exchange with a favorable response. All anti-MOG–positive patients with MS showed typical MS lesions on brain MRI. Longitudinal analysis up to 9 years revealed fluctuations and reappearance of anti-MOG reactivity. Epitope mapping indicated interindividual heterogeneity, yet intraindividual stability of the antibody response.Conclusions:Antibodies to MOG can be found in a distinct subgroup of adult MS with a specific clinical phenotype and may indicate disease heterogeneity.