Abstract
BACKGROUND AND OBJECTIVES: Anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis is the most common antibody-mediated encephalitis in adults older than 50 years. In addition to antibody effects, cytokines and chemokines drive neuroinflammation in other autoimmune encephalitides. However, their role in anti-LGI1 encephalitis is underexplored. We evaluated cytokine profiles in serum and CSF, correlating them with acute severity and long-term outcome. METHODS: Cytokine/chemokine levels from 57 untreated patients with anti-LGI1 encephalitis were measured in serum and CSF (34 paired samples) with a bead-based multiplex assay and compared with those of patients with noninflammatory neurologic disorders (serum = 24; CSF = 21). Clinical information including degree of severity (modified Rankin Scale, mRS) and 12-month functional outcomes (resume previous activities and work) was assessed. RESULTS: Patients with anti-LGI1 encephalitis exhibited an increased proinflammatory profile in CSF and serum, with elevated levels of IL-1β, IL-1RA, IL-6, IL-8, IL-10, IL-18, IL-35, IP-10, granzyme B, CX3CL1, MIG, TNFα, and SDF1. A higher CSF/serum IL-6 ratio correlated with disease severity at onset (mRS score >2: 1.67 [0.50-7.20] vs 0.39 [0.07-1.22], p = 0.0069). Elevated acute-phase serum IL-35 predicted poorer 12-month outcomes (81.34 vs 9.19 pg/mL in partial vs complete recovery, p = 0.0003). Increased B cell-related markers (IL-21, BAFF, APRIL, CXCL13) in CSF (all p < 0.05) were also observed. DISCUSSION: In this study, we show that the acute-phase IL-6 CSF/serum ratio and serum IL-35 levels in immunotherapy-naive patients with anti-LGI1 encephalitis are associated with disease severity and poor outcomes, respectively, highlighting their potential as biomarkers for risk stratification and therapeutic targeting.