Kv5.1 antibody in epilepsy patients with unknown etiology

• Published in: Epilepsy research Vol. 182; p. 106911
• Main Authors: Küçükali, Cem İsmail, Şengül, Büşra, Gezen-Ak, Duygu, Dursun, Erdinç, Erdağ, Ece, Akpınar, Gürler, Kasap, Murat, Karaaslan, Zerrin, Şirin, Nermin Görkem, Tektürk, Pınar, Baykan, Betül, Tüzün, Erdem
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2022
• Subjects: Animals; Antibody; Autoantibodies; Autoimmunity; Chromatography, Liquid; Epilepsy; HEK293 Cells; Humans; Immunoglobulin G; Kv5.1; Potassium channel; Rats; Tandem Mass Spectrometry; Autoimmunity; Kv5.1; Antibody; Potassium channel; Epilepsy
• ISSN: 0920-1211; 1872-6844
• DOI: 10.1016/j.eplepsyres.2022.106911

Neuronal autoantibodies and favorable response to immunosuppressive treatment have been described in patients with chronic epilepsy of unknown cause, suggesting autoimmune etiology. Our aim was to identify novel epilepsy-specific autoantibodies reactive with neuronal surface antigens. Sera of 172 epilepsy patients with unknown cause and 30 healthy controls were screened with indirect immunofluorescence to identify IgG reacting with primary rat neuronal cultures. Putative target autoantigens were investigated with immunoprecipitation (IP) and liquid chromatography-mass/mass spectrometry (LC-MS/MS) studies using SH-SY5Y cells. Validation of LC-MS/MS results was carried out by IP and immunocytochemistry assays. Antibodies to neuronal cell surface antigens were detected in 18 epilepsy patients. LC-MS/MS analysis identified voltage-gated potassium channel modifier subfamily F member 1 (KCNF1, Kv5.1) as the single common cell surface antigen in 4 patients with Lennox-Gastaut syndrome (n = 2), focal epilepsy of unknown cause (n = 1) and mesial temporal lobe epilepsy with hippocampal sclerosis (n = 1). These patients had the common features of early seizure onset and treatment-resistance. IP assays and co-localization (serum IgG and commercial Kv5.1-antibody) studies done with non-fixed Kv5.1-transfected HEK293 cells and primary neuronal cultures confirmed the presence of Kv5.1-antibody in 4 epilepsy patients identified by LC-MS/MS. Similar findings were not obtained by sera of other patients with epilepsy, patients with autoimmune encephalitis and healthy controls. The herein described novel neuronal surface antibody to Kv5.1 appears to be associated with treatment-resistant epilepsy of unknown cause. Exact clinical and pathogenic significance of this antibody remains to be elucidated. •Chronic epilepsy patients display serum IgG reactive with neuronal surface antigens.•Epilepsy patients with neuronal surface antibodies are often refractory to treatment.•Kv5.1 antibody was identified in four epilepsy patients with treatment resistance.•Autoimmunity may contribute to chronic epilepsy of unknown cause.