Peripheral Inflammatory Biomarkers in Chronic Autoimmune-Associated Epilepsy: An Exploratory Case-Control Study

Autoimmune-associated epilepsy (AAE) was recognized by the ILAE in 2017 as a distinct etiological category driven by chronic neuroinflammation rather than structural or genetic mechanisms. Reliable peripheral circulating inflammatory biomarkers to distinguish AAE from structural epilepsy remain lacking, potentially limiting timely recognition and evaluation for immunotherapy. In this observational case-control exploratory single-center study, plasma levels of 20 pro-inflammatory and 3 anti-inflammatory biomarkers, plus cerebrospinal fluid neurofilament light chain and HMGB1, were measured in 18 AAE patients, 33 non-autoimmune epilepsy patients and 16 healthy controls. AAE was defined using Dubey's APE2-based criteria. Univariate comparisons, ROC analysis, and binary logistic regression were performed.

Among the 25 biomarkers analyzed, plasma IL-12 showed the lowest nominal p-value in the global between-group comparison (p=0.038), with lower concentrations in AAE. However, no biomarker remained statistically significant after Benjamini-Hochberg false discovery rate correction (IL-12 q=0.366). ROC analysis yielded an AUC of 0.670 for IL-12 alone for distinguishing AAE from the remainder of the cohort. In an exploratory primary multivariable model including plasma IL-12, drug-resistant epilepsy (DRE) status, and EEG pattern, the apparent in-sample discriminative performance was higher than that of IL-12 alone (AUC = 0.771; 95% CI, 0.635-0.892).

Lower plasma IL-12 levels may reflect a peripheral immune association in chronic AAE. These findings are exploratory and hypothesis-generating and require replication in larger, prospectively recruited, independent cohorts.