Cytokine, Chemokine, and Neurofilament Light Chain Signatures in Anti-LGI-1 Encephalitis
Albert Aboseif1, Georgios Mangioris2, Binxia Yang2, Yahel Segal2, Divyanshu Dubey1, Eoin Flanagan1, Sarosh Irani3, Gregory Day3, Alfonso Lopez3, Jeffrey Britton1, Andrew McKeon1, Michel Toledano1, Ivana Vodopivec4, Sean Pittock1, Anastasia Zekeridou1
1Department of Neurology, 2Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, 3Department of Neurology and Neurosciences, Mayo Clinic College of Medicine, Jacksonville, FL, 4Roche Product Development-Neuroscience, F Hoffmann-La Roche, Basel, Switzerland
Objective:
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.
Background:
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.
Design/Methods:
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.
Results:
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.
Conclusions:
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.
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