Oligodendrocyte myelin glycoprotein as a novel target for pathogenic autoimmunity in the CNS.

Autoimmune disorders of the central nervous system (CNS) comprise a broad spectrum of clinical entities. The stratification of patients based on the recognized autoantigen is of great importance for therapy optimization and for concepts of pathogenicity, but for most of these patients, the actual target of their autoimmune response is unknown. Here we investigated oligodendrocyte myelin glycoprotein (OMGP) as autoimmune target, because OMGP is expressed specifically in the CNS and there on oligodendrocytes and neurons. Using a stringent cell-based assay, we detected autoantibodies to OMGP in serum of 8/352 patients with multiple sclerosis, 1/28 children with acute disseminated encephalomyelitis and unexpectedly, also in one patient with psychosis, but in none of 114 healthy controls. Since OMGP is GPI-anchored, we validated its recognition also in GPI-anchored form. The autoantibodies to OMGP were largely IgG1 with a contribution of IgG4, indicating cognate T cell help. We found high levels of soluble OMGP in human spinal fluid, presumably due to shedding of the GPI-linked OMGP. Analyzing the pathogenic relevance of autoimmunity to OMGP in an animal model, we found that OMGP-specific T cells induce a novel type of experimental autoimmune encephalomyelitis dominated by meningitis above the cortical convexities. This unusual localization may be directed by intrathecal uptake and presentation of OMGP by meningeal phagocytes. Together, OMGP-directed autoimmunity provides a new element of heterogeneity, helping to improve the stratification of patients for diagnostic and therapeutic purposes.

[Extended optic neuropathy with myelin oligodendrocyte glycoprotein antibodies]. / Le cas clinique du mois. Neuropathie optique étendue en présence d'anticorps «anti-myelin oligodendrocyte glycoprotein¼.

The discovery of autoantibodies targeting aquaporin-4 (AQP4) of astrocytes has improved the understanding and management of Neuromyelitis Optica Syndrome Disorders (NMO-SD), previously considered as a variant of multiple sclerosis. Later, the detection of MOG IgG1 antibodies, directed against an oligodendrocyte myelin glycoprotein, made it possible to distinguish pathologies with different clinical and prognostic particularities, then helping the clinician in his diagnostic and therapeutic approach. This clinical case aims to feature the clinical differences, prognosis and therapeutic solutions of these pathologies.

La découverte d'auto-anticorps ciblant l'aquaporine-4 (AQP4) des astrocytes a permis d'avancer dans la compréhension et la prise en charge du spectre des maladies de la neuromyélite optique (NMO-SD), antérieurement considérée comme une variante proche de la sclérose en plaques. Plus tard, la mise en évidence des anticorps MOG IgG1, dirigés contre une protéine de la myéline oligodendrocytaire, a permis de distinguer des pathologies avec des particularités cliniques et pronostiques différentes, pouvant aider le clinicien dans sa démarche diagnostique et thérapeutique. Ce cas clinique permet de détailler les différences cliniques et pronostiques ainsi que les solutions thérapeutiques de ces pathologies.

Confirmed enterovirus encephalitis with associated steroid-responsive acute disseminated encephalomyelitis: an overlapping infection and inflammation syndrome.

BACKGROUND: Inflammatory disorders of the central nervous system have generally been separated into infectious or immune-mediated aetiologies. However, there are emerging examples of confirmed infectious viral infection of the brain followed by secondary inflammation or autoimmunity that is amenable to immune suppressive therapies. METHODS: We report four children with confirmed enterovirus encephalitis (CSF enterovirus PCR positivity), who had MRI evidence of inflammatory demyelination compatible with ADEM. RESULTS: Two patients had a monophasic course, whereas two had a biphasic course. Serum myelin oligodendrocyte glycoprotein antibodies were negative in two tested patients, although all patients had mirrored CSF and serum oligoclonal bands. All four patients only improved with introduction of immune therapy (corticosteroids in three, corticosteroid and intravenous immunoglobulin in one). CONCLUSION: These cases provide a further example of the overlap between CNS infection and immune mediated CNS disease. Randomised controlled trials investigating immune therapies in encephalitis are required.