Abstract Details

Title Upregulated complement receptors correlate with Fc gamma receptor 3A-positive natural killer cells (NK) and natural killer-T cells (NKT) in neuromyelitis optica spectrum disorder.

Topic Autoimmune Neurology

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)
S1 - Virtual Abstract Data Blitz Presentations (8:00 AM-5:00 PM)

Poster/Presentation
Number 002

Objective

To clarify if NK and NKT cells are activated via complement in NMOSD.

Background

Inhibition of terminal complement in NMOSD using eculizumab has been shown to be helpful in preventing relapses but exactly how the drug is working is not clear. Similarly, genetic variants in the Fc Gamma receptor 3A are correlated with outcomes in NMOSD but the immune cells expressing those FcGR3A receptors are unknown. We compared FcGR3A expression on immune cells modulated by complement activity in NK cells and NKT cells in NMOSD to disease controls and healthy people.

Design/Methods

Peripheral blood cell (PBMC) samples from 45 patients with NMOSD with AQP4-IgG, 18 disease controls, and 19 normal controls were analyzed for FcGR3A expression and complement receptors in vitro.

Results At baseline, the number of NKT cells were increased in NMOSD (p < 0.001), but the proportion that were FcGR3A positive was lower compared to healthy and disease controls (p=0.0012). NK cell count was normal at baseline but also but the proportion that were FcGR3A positive was also relatively lower (p < 0.001). In both NK cells and NKT cells from NMOSD, C5 complement receptor expression was much higher compared to healthy and disease controls (p < 0.001 for both). We also evaluated activation markers CD69 and CD83, which were also much higher in NK and NKT cells from NMOSD patients.

Conclusions

Our results support a model of immunopathogenesis model in which complement pathway activation in NK/NKT cells upregulate FcGR3A expression that bind to antibody/antigen complexes. In the context of NMOSD, these complement-sensitive cells may be responsible for escalating autoimmune activity.

Authors/Disclosures
Shuhei Nishiyama, MD, PhD (Tohoku University Graduate school of Medicine) PRESENTER	Dr. Nishiyama has nothing to disclose.
	No disclosure on file
Itay Lotan, MD (Rabin Medical Center)	Dr. Lotan has nothing to disclose.
Friedemann Paul (Charite Universitatsmedizin in Berlin)	Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hoffmann-La Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol-Myers Squibb GmbH & Co. KGaA (BMS. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon Therapeutics GmbH. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Paul has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Paul has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Paul 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. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for sanofi. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for F&U Confirm. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb GesmbH. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MICE Service. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for VINDICO medical education. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Beijing Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sandoz Internation GmbH. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche Thailand. Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche . Dr. Paul has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion.
Michael Levy, MD, PhD, FAAN (Massachusetts General Hospital/Harvard Medical School)	Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Levy 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. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Levy has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various law firms. The institution of Dr. Levy has received research support from National Institutes Health.

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