AI Article Synopsis

  • Autoimmune disorders of the central nervous system (CNS) are diverse, and understanding the specific autoantigens is crucial for improving therapy and understanding disease causes.
  • Researchers studied oligodendrocyte myelin glycoprotein (OMGP) as a potential autoimmune target and found autoantibodies to OMGP in a small percentage of multiple sclerosis patients, a child with encephalomyelitis, and one patient with psychosis, but not in healthy controls.
  • The presence of OMGP-specific T cells in an animal model led to a new type of experimental autoimmune encephalomyelitis characterized by unusual inflammation, emphasizing the role of OMGP in patient diagnostic and therapeutic stratification.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706210PMC
http://dx.doi.org/10.1186/s40478-020-01086-2DOI Listing

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