Abstract Details

Title Use High-dimensional Immune Profiling to Study Peripheral Immune System and ALS Progression

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P6 - Poster Session 6 (8:00 AM-9:00 AM)

Poster/Presentation
Number 11-006

Objective

Identify immune signatures and their association with ALS progression.

Background ALS exhibits remarkable phenotypic variabilities in disease progression rate and survival time. Understanding the biological differences in this phenomenon can help identify predictive biomarkers and new therapeutic targets. Increasing evidence has emerged to support the role of immune system dysregulation in the pathophysiology of ALS. Clonally expanded CD4+ FoxP3+ regulatory T lymphocytes in the central nervous system inversely correlate with ALS progression. However, the mechanism underlying ALS progression disparity is still unclear.

Design/Methods

We utilize a high-dimensional immune profiling method-mass cytometry- to analyze the peripheral immune system and its correlation with ALS progression. Mass cytometry has advantages over traditional flow cytometry in that it can simultaneously analyze >40 cell surface markers and thereby identify unique immune cell subpopulations and effector status.

Fast progressors are defined as ALSFRS-R decline per month (ΔFRS/mo) >1.5, and slow progressors as ΔFRS/mo <0.5 and typical progressors as ΔFRS/mo of 0.5-1.5. Patients’ whole blood is banked and undergoes mass cytometry for in-depth immunophenotyping. We implement manual gating and machine learning to identify immune signatures. Manual analyses were performed in CytoBank. Unsupervised computational analysis was performed using VoPo Cell analysis (Stanley et al., 2020 Nature Communications).

Results

We found CD8 terminal effector memory T cells (TEMRA) in peripheral blood are expanded in slowly progressing ALS group; conversely, CD4-CD8-ϒδT cells are associated with fast-progressing diseases. We also found a statistically significant inverse correlation between TEMRA and ϒδ T cells. The functions of TEMRA and ϒδ T cells have not been well characterized in ALS. Further, We also found fewer circulating late NK cells in faster-progressing ALS.

Conclusions Our results indicate diverse immune perturbations in ALS that may play a role in disease progression. We plan to expand it to larger cohorts, laying the foundation for discovering new biomarkers and therapeutic targets.

Authors/Disclosures
Xiaoyan Li, MD (Duke University) PRESENTER	Dr. Li has nothing to disclose.
Baggio Evangelista (UNC Chapel Hill)	No disclosure on file
Rebecca Traub, MD, FAAN (University of North Carolina Chapel Hill)	Dr. Traub has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Traub 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. Traub has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Intellia. The institution of Dr. Traub has received research support from Alnylam Pharmaceuticals. The institution of Dr. Traub has received research support from Muscular Dystrophy Association (MDA). The institution of Dr. Traub has received research support from Ionis. The institution of Dr. Traub has received research support from Argenx. The institution of Dr. Traub has received research support from Pharnext. The institution of Dr. Traub has received research support from Immunovant. The institution of Dr. Traub has received research support from Takeda. Dr. Traub has received personal compensation in the range of $500-$4,999 for serving as a consultant with Department of Justice.
Natalie Stanley (UNC chapel hill)	No disclosure on file
Rick Meeker (University of North Carolina a)	No disclosure on file
Todd Cohen (University of North Carolina)	No disclosure on file

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