CD8 T Cell Immune Signatures in Autoimmune Myasthenia Gravis (N6.001)

Abstract

<h3>Objective:</h3> To explore the role of CD8 T cells in myathenia gravis. <h3>Background:</h3> Myasthenia gravis (MG) is a chronic autoimmune disease mediated by T cells. While previous studies have predominately focused on CD4 T cells in MG pathogen, our research seeks to examine the uncertain role of CD8 T cells. <h3>Design/Methods:</h3> Multi-color flow cytometry was performed on CD8 T cells among MG patients (N=42) with no immunosuppressant (No-IS), those treated with steroids and healthy controls (HC) (N=20). IsoPlexis single-cell platform was applied to a subset of patients to detect cytokine production prior to and post steroid treatment (N=12). NanoString RNA sequencing of 752 autoimmune related genes was performed on CD8 T cells to validate the cytokine changes (N=26). <h3>Results:</h3> Memory (CD27+) and Exhausted (CTLA4+, PD-1+, EMOES+) CD8 T cell were increased in No-IS MG patients. In unbiased Self-Organizing Maps (FlowSOM), central memory and CXCR5+ CD8 T cells were increased in No-IS compared to HC and decreased post treatment. Single-cell analysis detected elevated frequencies of effector and inflammatory cytokines, including granzyme B, IFN-g, IL-9, MIP-1b, TNF-a, IL-17A, GM-CSF, IL-12, and MIP-1a in the No-IS group. Effector and inflammatory cytokines and frequencies of polyfunctional CD8 T cells significantly decreased with steroids treatment. RNA sequencing assays are in process and results will be presented at the conference. <h3>Conclusions:</h3> Analysis of CD8 T cells demonstrates an effector phenotype with prominent polyfunctional inflammatory cytokine function in MG patients. Steroid treatment reduces the CD8 T cell proinflammatory phenotype. This data suggests CD8 T cells contribute to MG pathogenesis and may potentially serve as a biomarker for monitoring response to treatment. <b>Disclosure:</b> The institution of Dr. Li has received research support from Myasthenia Gravis Foundation of America. Dr. Juel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunovant. Dr. Juel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Juel has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accordant Health Services. The institution of Dr. Juel has received research support from argenx. The institution of Dr. Juel has received research support from Alexion. The institution of Dr. Juel has received research support from Janssen. The institution of Dr. Juel has received research support from NIH Rare Diseases Network. Ms. Karatz has nothing to disclose. Mrs. George has nothing to disclose. Dr. Guptill has received personal compensation for serving as an employee of argenx. Dr. Guptill has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Guptill has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Guptill has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Toleranzia. Dr. Guptill has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Takeda. Dr. Guptill has stock in argenx. The institution of Dr. Guptill has received research support from NIH. The institution of Dr. Guptill has received research support from MGFA. The institution of Dr. Guptill has received research support from PCORI. The institution of Dr. Guptill has received research support from Verily. The institution of Dr. Guptill has received research support from UNC. Dr. Guptill has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. The institution of Simon Gregory has received research support from NIH. Simon Gregory has received intellectual property interests from a discovery or technology relating to health care. Simon Gregory has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant with David H Murdock Research Institute.