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Abstract Details

Cytokine, Chemokine, and Neurofilament Light Chain Signatures in Anti-LGI-1 Encephalitis
Autoimmune Neurology
S7 - Autoimmune Encephalitis (3:42 PM-3:54 PM)
002
LGI-1-AE presentations vary in severity and long-term outcomes, suggesting immunobiological heterogeneity. Cytokines, chemokines, and NfL may be useful diagnostic, prognostic, and therapeutic biomarkers.

To evaluate the cytokine/chemokine profiles and neurofilament light chain (NfL) levels in anti-LGI-1 encephalitis (LGI-1-AE) and their association with disease severity and longitudinal clinical outcomes. 

We measured 17 cytokines/chemokines (IL-1-beta, IL-2, IL-4, IL-5, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-13, IL-17A, GM-CSF, TNF-alpha, IFN-gamma, CXCL9, CXCL10, CXCL13, BAFF) and NfL concentrations using a multiplex immunoassay system (ELLA, Bio-Techne) in CSF and paired serum from patients with LGI-1 AE evaluated at Mayo Clinic (01/2015-02/2024), and a laboratory-based cohort (05/2023–02/2024) without clinical information. Controls included patients with temporal lobe epilepsy (TLE), Alzheimer disease (AD), and other mixed non-inflammatory disorders (MNID). Analytes elevated in ≥15% of the LGI-1-AE cohort were evaluated for clinical associations.

We included 102 LGI-1-IgG positive patients (44 clinical, 58 lab-based), predominantly male (66%), with a median age of 68.5 years (8-85). In the clinical cohort, median time from symptom onset to CSF collection was 8 months (IQR, 3– 17.5) and 50% sustained a clinical relapse. Frequently elevated analytes were IL-6 (serum, 85%; CSF, 25%), IL-17A (serum, 57%; CSF, 23%), and IL-8/CXCL8 (serum, 39%; CSF, 18%). Levels of serum IL-6, serum/CSF IL-17A, and serum/CSF IL-8/CXCL8 were higher than MNID (p<0.05). Serum IL-6 and CSF IL-8/CXCL8 were higher than AD (p<0.05). Serum/CSF IL-17A was higher than TLE in the lab-based cohort (p<0.05).

Serum IL-6 elevation was associated with more frequent (≥1/day) seizures at disease onset (p=.04). Increased CSF NfL was associated with frequent (≥1/day; p=0.04) and intractable (p=0.01) seizures at last follow-up.

IL-6, IL-8/CXCL8, and IL-17A elevations suggest the role of a Th17 immune response in LGI-1-AE, informing potential therapeutic targets. IL-6 and NfL show promise as biomarkers of disease severity and longitudinal outcome in LGI-1-AE. 
Authors/Disclosures
Albert Aboseif, DO (Mayo Clinic Rochester)
PRESENTER 		Dr. Aboseif has a non-compensated relationship as a AAN Autoimmune Neurology Section -- 好色先生 Workgroup with AAN that is relevant to AAN interests or activities.
Georgios Mangioris, MD (Mayo Clinic) Dr. Mangioris has nothing to disclose.
Binxia Yang (Mayo clinic) Binxia Yang has nothing to disclose.
Yahel Segal, MD (Mayo Clinic) Dr. Segal has nothing to disclose.
Divyanshu Dubey, MD, FAAN (Mayo Clinic) The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.
Eoin P. Flanagan, MBBCh, FAAN (Mayo Clinic) The institution of Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. The institution of Dr. Flanagan has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Flanagan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pharmacy times. The institution of Dr. Flanagan has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for UCB. The institution of Dr. Flanagan has received research support from Viela Bio. The institution of Dr. Flanagan has received research support from UCB. The institution of Dr. Flanagan has received research support from Roche. Dr. Flanagan has received publishing royalties from a publication relating to health care. Dr. Flanagan has a non-compensated relationship as a Member of medical Advisory Board with The MOG Project that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Journal of The Neurologic Sciences that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial board member with Neuroimmunology Reports that is relevant to AAN interests or activities. Dr. Flanagan has a non-compensated relationship as a Editorial Board Member with Neurology, Neuroimmunology Neuroinflammation (N2) Journal that is relevant to AAN interests or activities.
Sarosh R. Irani, MD, PhD, FRCP, FEAN (Mayo Clinic) Dr. Irani has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for UCB, Immunovant, MedImmun, Roche, Janssen, Cerebral therapeutics, Biogen, Amgen, Argenex, Clarivate, IQVIA, BioHaven therapeutics, ADC therapeutics, Brain, CSL Behring, and ONO Pharma.. Dr. Irani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Irani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Irani has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Brain. Dr. Irani has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for LLPs. Dr. Irani has received intellectual property interests from a discovery or technology relating to health care. Dr. Irani has received intellectual property interests from a discovery or technology relating to health care. Dr. Irani has received intellectual property interests from a discovery or technology relating to health care.
Gregory S. Day, MD, MSc, FAAN (Mayo Clinic) Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Parabon Nanolabs. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vigil Neuro. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from Chan Zuckerberg Initiative. The institution of Dr. Day has received research support from Alzheimer's Association. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Amgen Pharmaceuticals. The institution of Dr. Day has received research support from AVID Radiopharmaceuticals. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with 好色先生. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing 好色先生, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Ionis Pharmaceuticals. Dr. Day has a non-compensated relationship as a Clinical Director with Anti-NMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities.
Alfonso S. Lopez, MD (Mayo Clinic) Dr. Lopez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Lopez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech .
Jeffrey W. Britton, MD, FAAN (Mayo Graduate School of Medicine) Dr. Britton has received personal compensation in the range of $0-$499 for serving as a Online course with American Clinical Neurophysiology Society.
Andrew McKeon, MD (Mayo Clinic) The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care.
Michel Toledano, MD (Mayo Clinic) Dr. Toledano has nothing to disclose.
Ivana Vodopivec, MD (F Hoffmann-La Roche AG) Dr. Vodopivec has received personal compensation for serving as an employee of Roche. An immediate family member of Dr. Vodopivec has received personal compensation for serving as an employee of Novartis. Dr. Vodopivec has stock in Roche.
Sean J. Pittock, MD, FAAN (Mayo Clinic Dept of Neurology) Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Alexion/AstraZeneka. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic) The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.