Liquid Biomarkers in Autoimmune Encephalitis and Autoimmune-Associated Epilepsy

Autoimmune encephalitis (AE) and autoimmune-associated epilepsy represent a rapidly evolving field in neurology where the immune system mistakenly targets central nervous system components, triggering severe inflammation, psychiatric symptoms, cognitive decline, and intractable seizures. The discovery of neural antibodies, targeting either intracellular antigens (like Hu or Ma2) or surface receptors (such as NMDAR or LGI1), has revolutionized diagnostic paradigms. Notably, chronic epilepsy patients, who do not fulfill the clinical criteria for autoimmune encephalitis may also harbor neural antibodies with pathogenic significance, cerebral immune cell infiltration, CSF inflammation and good response to immunotherapy thus prompting the term autoimmune-associated epilepsy. Biomarkers serve as essential tools for early diagnosis, differentiating autoimmune etiologies from infectious or neurodegenerative diseases, and guiding immunotherapy. Beyond diagnostic antibody testing in serum and CSF, emerging liquid biomarkers include cytokine/chemokine profiles, neurofilament light chain (NfL) as a marker of axonal damage, and peripheral blood/CSF immune cells. Identifying and validating these biomarkers is vital to tracking disease progression, predicting long-term cognitive outcomes, and tailoring personalized treatment protocols for affected patients.Despite major breakthroughs, delayed diagnosis and treatment resistance remain critical challenges in AE, autoimmune-associated epilepsy and status epilepticus. Many patients lack detectable classical antibodies, leading to "seronegative" misdiagnosis, missed therapeutic windows, and irreversible neurological damage. Furthermore, it is imperative to predict which patients will develop chronic, drug-resistant epilepsy and which will achieve full remission. This Research Topic aims to overcome this by focusing on discovering novel, ultra-sensitive diagnostic targets. Recent advances in high-throughput proteomics, single-cell RNA sequencing, and machine learning are successfully mapping complex cytokine networks. Leveraging these technologies will allow researchers to validate non-antibody biomarkers, such as specific microRNA profiles. Alternative diagnostic methods may also include functional assays assessing the impact of neural antibodies on cultured neurons. This Research Topic highlights a multi-parametric approach that will ultimately enable earlier intervention, precise monitoring of immunotherapy response, and the discovery This Research Topic welcomes all article types accepted by the journal that advance the discovery, validation, and clinical application of biomarkers in AE and autoimmune-associated epilepsy:• Novel Antibody Discovery: Identification of new cell-surface, intracellular, or synaptic autoantibodies.• Seronegative Autoimmune Encephalitis: Diagnostic criteria, biomarker panels, and treatment strategies for antibody-negative cases.• Predictive Biomarkers for Epilepsy: Serum/CSF markers that identify patients at high risk for chronic, drug-resistant epilepsy.• Surrogate Markers of Disease Activity: Utilizing NfL, tau, or specific microRNAs to track neuroaxonal injury and therapeutic response. • Inflammatory and Cytokine Profiling: Mapping CSF/serum chemokines, cytokines, and immune cell phenotypes to understand underlying pathogenic mechanisms.• Autoimmunity in chronic epilepsy: Investigating underlying autoimmune mechanisms in chronic epilepsy patients without overt (clinical/radiological) encephalitis Topic editors: Erdem Tüzün, Betül Baykan, Rabia Gokcen Gozubatik-Celik, Matteo Gastaldi Source: https://www.frontiersin.org/research-topics/85097/liquid-biomarkers-in-autoimmune-encephalitis-and-autoimmune-associated-epilepsy