Immune signatures link myelin oligodendrocyte glycoprotein antibody–associated disease to other autoantibody-mediated conditions

Myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) is a recently defined neurological autoimmune condition. The pathogenesis of the disease remains poorly understood, and no specific therapies are currently approved. Here, a comprehensive single-cell immunophenotyping of peripheral blood mononuclear cells from two independent cohorts of patients with MOGAD revealed pronounced immune perturbations in MOGAD when compared with healthy controls and patients with multiple sclerosis. Patients with MOGAD displayed an expansion of CXCR5 − CD21 − activated naïve and double-negative B cell subsets, a feature shared with patients with systemic lupus erythematosus. In addition, we observed altered Fc gamma receptor expression in natural killer cells, monocytes, and dendritic cells. Within the T cell compartment, CXCR3 + CD4 + memory T cells were reduced in the circulation of patients with MOGAD compared with healthy controls, and this result was mirrored in a transgenic mouse model that showed retention of these cells in the inflamed central nervous system. Together, these results demonstrate profound systemic immune cell alterations in MOGAD and contribute to a better understanding of this distinct disease entity.