HMGB1/CXCL12-Mediated Immunity and Th17 Cells Might Underlie Highly Suspected Autoimmune Epilepsy in Elderly Individuals.

Purpose: Late-onset epilepsy due to autoimmune dysfunction has been reported. However, definitive diagnosis requires positive antibody results. As a result, patients with negative antibody results, but presenting with classical manifestation of autoimmune epilepsy, may be managed as suspected cases. In this study, we aim to isolate and profile the concentration of cytokines/chemokines in the cerebrospinal fluid (CSF) and the serum to ascertain if they could act as alternative diagnostic biomarkers.

Patients And Methods: Twenty patients aged ≥50 years were considered in this study. Ten patients were diagnosed with suspected autoimmune epilepsy (sAE) based on clinic manifestation, electroencephalogram, magnetic resonance imaging, and with negative antibody results of the serum and the CSF. The equivalent control group exhibited neurological disorders due to non-inflammatory pathologies. Serum and CSF were analyzed for cytokines/chemokines concentration, including interleukin (IL)-6, IL-10, IL-17, chemokine (C-X-C motif) ligand (CXCL)12 and CXCL13, as well as high-mobility group box protein 1 (HMGB1) and B cell activation factor (BAFF)).

Results: The CSF levels of IL-6, IL-17, HMGB1, and CXCL12 were significantly higher in the sAE group than in the control group. There was no difference in the CSF levels of IL-10, CXCL13 and BAFF. The serum levels of HMGB1 and CXCL12 were elevated in the sAE group compared with the control group, and there was no statistical difference in the serum levels of IL-6, IL-10, IL-17, CXCL13, and BAFF between the two groups.

Conclusion: Our study shows that cytokines/chemokines may act as alternative biomarkers for diagnosis of sAE. The activation of both HMGB1/CXCL12-mediated immunity and T helper cells 17 (Th17) cells may be playing a central role in the pathogenesis of sAE. We suggest that cytokines/chemokines be treated as adjuvant biomarkers, instead of solely relying on antibody screening test. However, a larger cohort in a prospective approach is required to validate our findings.