CD56^dimCD16^dim/- NK cells are elevated in patients with autoantibody-mediated neurologic diseases and indicate cytotoxic activity

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Presentation Time: 05:45 PM - 06:00 PM
Abstract ID: 4887 - B

Presenting Author:
Soumya S. Yandamuri , Postdoctoral Fellow at Yale Sch. of Med.

Abstract:

Neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody disease (MOGAD), and autoimmune myasthenia gravis (MG) are autoantibody-mediated neurologic conditions where autoantibodies are capable of antibody-dependent cellular cytotoxicity (ADCC), a natural killer (NK) cell mediated effector function. Whether ADCC occurs in patients with these conditions is not clear; thus, we characterized circulatory NK cells to elucidate their role in pathology. NK cells from NMOSD patients and MG patients with elevated disease burden exhibited reduced ADCC and CD56^dimCD16^hi NK cells, and elevated CD56^dimCD16^dim/- NK cells. We determined that ADCC induces a similar phenotypic shift in vitro, suggesting ADCC activity in NMOSD and MG. Bulk RNA sequencing distinguished the CD56^dimCD16^dim/- population from other NK cell subsets. Similarly, immunophenotyping of NK cell markers, functional proteins, and receptors showed that the CD56^dimCD16^dim/- subset exhibits a unique profile while still maintaining expression of characteristic NK markers. They exhibit reduced perforin and granzyme and elevated HLA-DR, trogocytosis, and chemokine receptors like CCR7. In contrast with NMOSD and MG, MOGAD NK cells did not exhibit any perturbations. In summary, CD56^dimCD16^dim/- NK cells are a distinct peripheral blood immune cell population in humans elevated upon prior cytotoxic activity with potential as a disease biomarker.