Abstract Details

Title Comparative Immune Cell and Cytokine Phenotyping in Neuromyelitis Optica Spectrum Disorder Patients from the CIRCLES Cohort

Topic Autoimmune Neurology

Presentation(s) P14 - Poster Session 14 (8:00 AM-9:00 AM)

Poster/Presentation
Number 15-004

Objective Relative frequencies of immune cell phenotypes and cytokine profiles were analyzed to seek candidate biomarkers correlating with specific disease characteristics, clinical manifestations or therapeutic responses in NMOSD patients vs. healthy controls.

Background Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune, demyelinating inflammatory disorder of the central nervous system. Despite recent insights into disease pathogenesis, identities of biomarkers for clinical remission, relapse and treatment response have been elusive.

Design/Methods Sera and peripheral blood mononuclear cells (PBMC) from patients meeting NMOSD diagnostic criteria or healthy control subjects in the Collaborative International Research in Clinical & Longitudinal Experience for NMOSD Studies (CIRCLES) were analyzed using high-throughput methods. Validated flow cytometry measured relative frequencies of T and B lymphocyte subsets, monocytes, natural killer (NK) cells and dendritic cells in PBMC of 14 patients vs. 15 controls. In parallel, 47 soluble cytokines were analyzed in 27 NMOSD and 11 control sera using multiplex affinity proteomics. Univariate and principal component logistic regression were used to assess predictive values of candidate biomarkers for classifying disease status in NMOSD.

Results Patients had significantly smaller proportions of CD16+/CD56+ NK cells, Tc1 and Tc2 CD8+ cells vs. healthy controls. Among other patterns, significantly increased soluble eotaxin-1, IL-6, IL-17F and B-cell activating factor (BAFF) were observed in patient vs. healthy control sera. Using principal component analysis, the predictive area under the curves were 0.75 for flow cytometry, and averaged 0.80 for soluble cytokines.

Conclusions This systematic, discovery-driven analysis of immune cell phenotypes and soluble cytokines revealed significantly different frequencies of CD8+ and NK cell subsets, and a distinct profile of elevated serum cytokines in NMOSD patients vs. healthy controls. Research is ongoing to identify biomarkers that reliably correlate with or predict disease status, relapse and therapeutic response.

Authors/Disclosures
Soumya S. Yandamuri, PhD (Yale School of Medicine) PRESENTER	Dr. Yandamuri has nothing to disclose.
	No disclosure on file
Aditi Sharma, MBBS (University of Utah)	Dr. Sharma has nothing to disclose.
	No disclosure on file
Chrysoula Zografou (Yale Univ Sch of Medicine, Dept of Neur)	No disclosure on file
Anthony K. Ma, MD (The Mount Sinai Hospital)	Mr. Ma has nothing to disclose.
	No disclosure on file
Lawrence Cook, PhD (University of Utah Data Coordinating Center)	The institution of Dr. Cook has received research support from CDC. The institution of Dr. Cook has received research support from The Guthy-Jackson Charitable Foundation. The institution of Dr. Cook has received research support from Utah Highway Safety Office. The institution of Dr. Cook has received research support from NIH.
	No disclosure on file
Terry Smith	Terry Smith has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Horizon. Terry Smith has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Immunovant. Terry Smith has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Terry Smith has received intellectual property interests from a discovery or technology relating to health care.
Michael R. Yeaman, PhD (UCLA)	Dr. Yeaman 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. Yeaman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genentech-Roche. Dr. Yeaman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. The institution of Dr. Yeaman has received research support from National Institutes of Health. The institution of Dr. Yeaman has received research support from U.S. Department of Defense. Dr. Yeaman has received intellectual property interests from a discovery or technology relating to health care. Dr. Yeaman has received intellectual property interests from a discovery or technology relating to health care.
Kevin C. O'Connor, PhD (Yale University School of Medicine)	Kevin C. O'Connor, PhD has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Immunovant. Kevin C. O'Connor, PhD has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenx. Kevin C. O'Connor, PhD has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Neurocrine. Kevin C. O'Connor, PhD has stock in Cabaletta. The institution of Kevin C. O'Connor, PhD has received research support from Seismic. The institution of Kevin C. O'Connor, PhD has received research support from Argenx. Kevin C. O'Connor, PhD has received intellectual property interests from a discovery or technology relating to health care.
Jacinta Behne (The Guthy-Jackson Charitable Foundation)	Ms. Behne has nothing to disclose.
	No disclosure on file

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Abstract Details