Abstract Details

Title CSF Host Transcriptomics Differentiates Infectious Encephalitis from Autoimmune Encephalitis

Topic Autoimmune Neurology

Presentation(s) S16 - Autoimmune Neurology: Immune Profiling and Antibody Detection (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

Objective To identify cerebrospinal fluid (CSF) gene expression signatures that differentiate infectious encephalitis (IE) from autoimmune encephalitis (AE) using metagenomic next-generation sequencing (mNGS).

Background Rapid and accurate distinction between IE and AE is critical given earlier treatment improves outcomes, yet immunosuppression poses significant risks in cases of undiagnosed infection. Current diagnostic tools – such as targeted pathogen-specific testing for IE and antibody panels for AE – are limited by long turnaround times and risks of false negatives. CSF host transcriptomics analysis via mNGS provides a novel approach by directly measuring the host immune response through changes in gene expression and has the potential to identify biomarkers and immune mechanisms to more rapidly and accurately differentiate IE from AE.

Design/Methods CSF bulk RNA-sequencing was performed in a cohort of patients with antibody-positive AE and confirmed IE. Differential gene expression and gene ontology (GO) pathway analyses were conducted to identify immune signatures distinguishing the two cohorts.

Results Forty-seven patients were included for analysis: 11 with IE (all viral) and 36 with AE (21 anti-NMDAr, 9 GAD65, 3 LGI1, 3 GABA-B). Median age was 10 (45% male) and 22.5 years (36% male) for IE and AE, respectively. A total of 1,310 genes were differentially expressed between IE and AE (adjusted p<0.05). Of these, 805 genes were upregulated in IE, including key antiviral and type 1 interferon-related genes. Top enriched GO pathways included “defense response to virus”, “regulation of the innate immune response”, and “interferon-beta production”.

Conclusions IE and AE demonstrate distinct CSF gene expression profiles. IE is characterized by robust activation of antiviral and interferon-mediated pathways. CSF host transcriptomics may serve as a powerful diagnostic tool to differentiate encephalitis etiologies and guide early treatment. Ongoing work is the application of machine learning approaches to develop a predictive classifier for IE versus AE.

Authors/Disclosures
Mary Karalius, MD (UCSF) PRESENTER	Dr. Karalius has nothing to disclose.
Greer Waldrop, MD (UCSF)	Dr. Waldrop has nothing to disclose.
Ravi Dandekar	Ravi Dandekar has nothing to disclose.
Shiyin Wang	Ms. Wang has nothing to disclose.
Stephen Ray, PhD	Dr. Ray has nothing to disclose.
Kelsey Zorn	Ms. Zorn has nothing to disclose.
Sukhman Sidhu (University of California San Francisco)	Ms. Sidhu has nothing to disclose.
Asritha Tubati (University of California, San Francisco)	Asritha Tubati has nothing to disclose.
Chloe Gerungan	Chloe Gerungan has nothing to disclose.
Michael R. Wilson, MD, FAAN (University of California San Francisco)	Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ouro Medicines. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vertex Pharmaceuticals. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Indapta Therapeutics. Dr. Wilson has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Delve Bio. Dr. Wilson has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Cambridge Medical Experts. Dr. Wilson has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Dunham Hallmark. Dr. Wilson has stock in Delve Bio. The institution of Dr. Wilson has received research support from Genentech / Roche. The institution of Dr. Wilson has received research support from NIH. The institution of Dr. Wilson has received research support from Novartis. The institution of Dr. Wilson has received research support from National Multiple Sclerosis Society. The institution of Dr. Wilson has received research support from Fanconi Anemia Research Foundation. The institution of Dr. Wilson has received research support from Department of Defense. The institution of Dr. Wilson has received research support from Chan Zuckerberg Initiative. The institution of Dr. Wilson has received research support from Kyverna Therapeutics. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received intellectual property interests from a discovery or technology relating to health care. Dr. Wilson has received personal compensation in the range of $10,000-$49,999 for serving as a Expert Witness with US Dept of Justice.

��ɫ��

��ɫ��