Cytokine analysis for seronegative autoimmune epilepsy diagnosis

This study found a unique profile of 14 elevated cytokines, potential biomarkers, in patients with a specific type of epilepsy (snAAE) that doesn’t respond to traditional antibody tests.

Background

Autoimmune-associated epilepsy (AAE) is a significant contributor to drug-resistant epilepsy cases, characterized by a positive response to immunotherapies. Traditional diagnostic methods rely on identifying known neuronal autoantibodies in patient serum or cerebrospinal fluid. This approach has proven effective in diagnosing seropositive AAE (spAAE) but fails to diagnose seronegative AAE (snAAE), a subset of patients who respond to immunotherapy but lack detectable autoantibodies.

This inability to diagnose snAAE poses a significant challenge for patients as they often face difficulty obtaining insurance coverage for needed immunotherapies. Current diagnostic frameworks for AAE primarily focus on autoantibody detection, which has proven insufficient in diagnosing snAAE. Expanding existing autoantibody screens has not significantly enhanced diagnostic accuracy for snAAE. This suggests that relying solely on autoantibody detection is inadequate, and alternative approaches are needed to identify immune dysregulation in these patients and enable timely treatment using immunotherapies.

Technology description

This study identifies a profile of 14 cytokines that are significantly elevated in patients with clinically suspected seronegative autoimmune-associated epilepsy (snAAE). These cytokines, including IL-6, IL-8, IL-10, VEGF-A, and TNF-b, are proposed as potential biomarkers for snAAE diagnosis. The study also found notable increases in other cytokines like EGF, MCP-3, IL-1A, IL-13, IL-16, and IL-28A, also contributing to the distinct cytokine signature of snAAE.

This approach differentiates itself from traditional diagnostic methods for autoimmune epilepsy where it detects a snAAEs, subset of cases who respond to immunotherapy but lack detectable autoantibodies. This study suggests that focusing on cytokine analysis rather than solely relying on autoantibody detection could offer a more effective diagnostic approach for snAAE, potentially leading to earlier identification and treatment using targeted immunotherapies.

Benefits

Early diagnosis and treatment – via earlier identification of snAAE, leading to faster intervention with immunotherapies and better treatment outcomes.
Targeted treatment using immunotherapy – use of more targeted and effective immunotherapies tailored to the specific cytokine profile of the patient.
Improved diagnostic accuracy – this diagnostic approach is more effective than relying solely on autoantibody detection, which often fails in snAAE cases.
Objective disease monitoring – cytokine levels could be used to monitor disease activity and severity, like their use in other inflammatory conditions.
Accessibility and affordability – cytokine testing is becoming increasingly affordable and accessible in clinical settings, making it a practical tool for diagnosis and monitoring.