High dimensional mass cytometry analysis unravels distinct profiles of peripheral blood mononuclear cells in patients with neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein associated disease or in health

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Abstract
Background Neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein-antibody associated disease (MOGAD) are rare demyelinating diseases of the central nervous system but can cause severe disability. Although these two diseases share inherent similarities, they show different pathogenesis, clinical features, and treatment response. Investigation performed by a more powerful approach is needed. Methods Cytometry by time-of-flight mass spectrometry (CyTOF) was used to cluster and phenotype the immune cell subsets in peripheral blood mononuclear cells (PBMCs) isolated from patients with NMOSD or MOGAD and healthy controls (HC). RNA sequencing was used to screen pivotal genes. The obtained algorithm-based data were further verified through traditional flow cytometry and qPCR analysis. Results We identified 29 cell clusters and found several immune cluster changes between NMOSD and MOGAD. Interestingly, no significant differences were found in the B cells fraction between patients and HC group. Immunity dysfunction was mainly attributed to changes of diverse subsets in T cells and mononuclear phagocytes (MNPs). Similar properties of two distinct CD56 + natural killer (NK) cell phenotypes and transcription factor T-bet + or chemokine receptor CCR2 + subsets were shown between patients and health. Conclusions Our results show an overview of the circulating PBMCs landscape of NMOSD and MOGAD patients compared to that of HC. Our data reveal that different immune phenotypes may involve in the distinct pathogenesis of NMOSD and MOGAD and highlight T cells or MNPs as a potential target for precision treatment.

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