Antibody-Dependent Cellular Phagocytosis and Cytotoxicity in Patients With LGI1 and CASPR2 Encephalitis

Abstract

This database includes the raw data linked with the paper “ Antibody-dependent cellular-phagocytosis and -cytotoxicity in patients with LGI1 and CASPR2 encephalitis”. Objective: Antibodies against LGI1 and CASPR2 (LGI1/CASPR2-IgG) associate with forms of autoimmune encephalitis (AE) that improve with immunotherapy but often show long term neuropsychiatric sequelae. We aimed to investigate autoantibodies effector functions as prognostic biomarkers in patients with LGI1/CASPR2 AE. Methods: We included patients with LGI1/CASPR2 AE, sufficient clinical information and one serum sample available. We assessed the functional profile of LGI1/CASPR2-IgG using in-vitro cell-based assays for complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular-cytotoxicity (ADCC). Outcome was measured using the modified Rankin Scale (mRS) and the Clinical Assessment Scale in AE (CASE). Results: we enrolled 55 patients (LGI1=31, CASPR2=24). Co-existent ADCC and ADCP (ADCC+/ADCP+) were found in 28/55 patients (10/31 with LGI1 and 18/24 with CASPR2), while an isolated ADCP (ADCC-/ ADCP+) was detected in 15 patients (12 with LGI1-IgG and 3 with CASPR2-IgG), and an isolated ADCC (ADCC+/ADCP-) in two LGI1-IgG-positive patients. As most patients (84%) showed a combination of IgG1/IgG3 and IgG4 subclass, no specific functional profiles could be identified according to the predominant subclass. Quantitative ADCP levels showed only a moderate correlation with CASPR2/LGI1-IgG titer (rho=0.35, p=0.02), while ADCC showed a moderate/strong correlation (rho=0.54, p=0.002). None of the patients showed CDC activation. In a multivariate logistic regression model (including functional profile, rituximab treatment, relapsing course and cognitive impairment at onset) the ADCC+/ADCP+ profile was the only predictor of poor outcome (mRS>1, (OR: 10.97 [CI, 1.96–106.9]; p=0.014). Conclusions: ADCC and ADCP, but not CDC, are common effector functions of LGI1/CASPR2-IgG, and their presence correlates with long-term poor outcome, suggesting that they might represent a useful prognostic biomarker. We provide the proof-of-principle for a framework that could be applied to other antibody-mediated conditions of the nervous system.

The authors' abstract, as published at the source. Neurology Neuroimmunology & Neuroinflammation, 2026 · DOI ↗