Abstract Details

Title T Regulatory Cells Mediate ALS Progression and Survival

Topic Anterior Horn

Presentation(s) P02 - (-)

Poster/Presentation
Number 166

Objective

Background BACKGROUND: In the mouse model of ALS, Tregs have a documented neuroprotective role slowing disease progression. The presence of T lymphocytes at sites of neuronal injury in the spinal cord of ALS patients prompted us to evaluate whether Tregs are altered with disease progression and whether these alterations are predictive of disease progression rates.

Design/Methods DESIGN/METHODS: Peripheral blood leukocytes from 54 ALS patients at all stages of disease and 33 control volunteers were assessed by flow cytometry and quantitative RT PCR. A second group of 102 ALS patients from early stage disease were assessed and followed for 3.5 years.

Results RESULTS: Both the numbers of Tregs and their FoxP3 (a transcription factor required for Treg function) protein expressions were reduced in rapidly progressing ALS patients and inversely correlated with progression rates. The mRNA levels of FoxP3, Gata3 (a Th2 transcription factor), TGF?, and IL4 were reduced in rapidly progressing patients and inversely correlated with progression rates. Both FoxP3 and Gata3 were more accurate prognostic indicators of progression rates than the time from first symptom to first exam. No differences in IL10, Tbx21 (Tbet, a Th1 transcription factor), or IFN? expression were found between slowly and rapidly progressing patients. A 3.5-year prospective study with a second larger cohort revealed that early reduced FoxP3 levels were indicative of progression rates at time of collection and predictive of future rapid progression and attenuated survival: 35% of patients with low FoxP3 were on a ventilator or were deceased compared to 13% of patients with high FoxP3.

Conclusions CONCLUSIONS: These results indicate that Tregs and Th2 lymphocytes influence disease progression rates. Importantly, early reduced FoxP3 levels can be used to identify rapidly progressing patients, invaluable for patient management and clinical trial development.

Authors/Disclosures
Jenny Henkel, PhD PRESENTER	No disclosure on file
David R. Beers, PhD (Houston Methodist Neurological Institute)	No disclosure on file
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ)	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Clario.
Weihua Zhao, MD (Houston Methodist Neurological Institute, Houston Methodist Hospital)	No disclosure on file
	No disclosure on file
Stanley H. Appel, MD, FAAN (Methodist Neurological Institute)	Dr. Appel has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Appel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eledon. The institution of Dr. Appel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Implicit. The institution of Dr. Appel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Coya Therapeutics. Dr. Appel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Muscular Disease Association. Dr. Appel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for ALS Therapy Development Institute. Dr. Appel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for ALS Finding a Cure. Dr. Appel has stock in Stock holdings in retirement acct at Fidelity. The institution of Dr. Appel has received research support from Coya Therapeutics.
Sven Schippling (University of Neurology)	No disclosure on file

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