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The Role of T cells in children with anti-NMDA Receptor Encephalitis

Award Number: K23NS142667
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/15/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2030

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The Role of T cells in children with anti-NMDA Receptor Encephalitis - PROJECT SUMMARY/ABSTRACT Autoimmune encephalitis is a disease in which inflammation occurs in the brain and can cause high morbidity and mortality. Anti-NMDA receptor encephalitis (NMDARE) is the most common cause of encephalitis and occurs in children and adults. Those who survive NMDARE develop long-term neuropsychological sequelae, including developmental problems in children. NMDARE treatments target antibodies and B-cells but 30% do not respond to these treatments and require additional T-cell targeting therapies which have increased toxicities and side effects. A lack of a prognostic biomarker is a major gap in the treatment of NMDARE. Having a biomarker at the time of diagnosis to guide treatment optimal treatment in NMDARE can result in improved outcomes. This five-year career development plan proposes using advanced immunological assays including high-dimensional flow cytometry and single cell RNAsequencing (scRNAseq) to identify the role of T cells in NMDARE, focusing on T helper 17 cells (Th17), a subset of CD4+ T cells that is pathogenic in other autoimmune diseases. The hypothesis is that severe NMDARE is marked by elevated Th17 cells (identified through blood and CSF cytokines, flow cytometry for immune cell profiling, and transcriptomics for identifying functional elements of the immune cell’s genome) and Th17 cells could be a prognostic biomarker. The aims of this NMDARE study is to 1) characterize how timing of T cell treatments affect outcomes in a retrospective cohort of 19 sites and 362 children with NMDARE, 2) assess blood and CSF Th17 cells and related cytokines using flow cytometry and electrochemiluminescence immunoassays respectively, and 3) use scRNAseq to identify NMDA receptor specific T cells and to assess if intracellular pathways are different in Th17 cells from NMDARE compared to controls. This proposed work supports the mission of the National Institute of Neurological Disorders and Stroke in increasing knowledge about how the neuroinflammation affects the brain and to use that knowledge to reduce the disease burden in NMDARE but also other neuroinflammatory conditions. The candidate is committed to a career in the investigation of neuroinflammatory diseases to understand the pathogenic immune pathways, and to improve treatments, by identifying optimal treatment strategies by biomarkers and novel therapeutic targets. The candidate will train in performing laboratory techniques such as high-dimensional flow cytometry and scRNAseq, and advanced statistical methods. This training would equip the candidate to be a unique pediatric translational neuroimmunology clinician-scientist. Overall this project proposes a novel translational approach to understanding NMDARE. While NMDARE is rare, the candidate will leverage CONNECT, a multi-center prospective cohort to carry out this study, and the results of this study could apply to other neuroinflammatory diseases such as multiple sclerosis to improve patient outcomes, including neurodevelopmental outcomes in children.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $219,645 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/7/2025	NEW	$219,645
														Subtotal = $219,645

Grand Total All Awards = $219,645

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The Role of T cells in children with anti-NMDA Receptor Encephalitis

Award Number: K23NS142667

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/15/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2030

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