{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T13:17:38Z","timestamp":1779110258842,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Autoimmune encephalitis (AE) is characterized by inflammatory processes in the central nervous system and frequently presents with seizures. Even though an ictogenic potential has been shown for some antibodies against neuronal surface antigens (NSAbs), AE pathophysiology is complex, and NSAbs\u2010independent mechanisms are likely to contribute to seizures. We investigated whether the secretome released by peripheral blood mononuclear cells (PBMCs) from AE patients contributes to seizure generation independently of NSAbs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PBMCs were isolated from 19 patients with AE (including both those with and those without detectable NSAbs) and 13 healthy volunteers. After 6 h in culture, the PBMC supernatant (secretome) was infused into a heterologous in\u00a0vitro whole guinea pig brain preparation. Neurophysiological activity was monitored in the isolated in\u00a0vitro guinea pig brain preparation during coperfusion of PBMC\u2010derived supernatant (secretome) with the endotoxin lipopolysaccharide and human recombinant serum albumin, to induce and mimic, respectively, a mild functional blood\u2013brain barrier impairment. Morphological analysis of ionized calcium\u2010binding adapter molecule 1\u2010positive glial cells was performed in these brains after the electrophysiological experiment. Secretome obtained after 6\u2009h in culture was analyzed with the Multiplex ELLA array system for inflammatory mediator detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Electrophysiological recordings and immunofluorescence analyses revealed that the secretome from PBMCs derived from AE patients induced seizurelike events and microglial activation in our in\u00a0vitro brain preparation. Multiplex ELLA immunoassay analysis showed significantly lower concentration of interleukin (IL)\u201010, IL\u20101Ra, tumor necrosis factor\u2010\u03b1, IL\u20102, and IL\u20106 in the secretome of PBMCs derived from AE patients compared to healthy subjects. IL\u20101\u03b2 levels were comparable in the secretome of PBMCs derived from AE and healthy subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Our findings suggest, for the first time, that peripheral inflammatory mediators could represent a trigger factor for seizure activity in AEs, beyond a possible antibody\u2010mediated mechanism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18600","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T15:31:21Z","timestamp":1755531081000},"page":"5055-5066","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Peripheral blood mononuclear cell secretome from patients with autoimmune encephalitis promotes seizures in\u00a0vitro"],"prefix":"10.1111","volume":"66","author":[{"given":"Sara","family":"Prevosti","sequence":"first","affiliation":[{"name":"Epilepsy Unit Fondazione IRCCs Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico \u201cCarlo Besta\u201d  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Passalacqua","sequence":"additional","affiliation":[{"name":"Epilepsy Unit Fondazione IRCCs Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico \u201cCarlo Besta\u201d  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina","family":"Regondi","sequence":"additional","affiliation":[{"name":"Epilepsy Unit Fondazione IRCCs Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico \u201cCarlo Besta\u201d  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giada","family":"D'Ambrosio","sequence":"additional","affiliation":[{"name":"Epilepsy Unit Fondazione IRCCs Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico \u201cCarlo Besta\u201d  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3649-8990","authenticated-orcid":false,"given":"Alessandra","family":"Morano","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Policlinico Umberto I Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Romoli","sequence":"additional","affiliation":[{"name":"Neurology and Stroke Unit, Department of Neuroscience Maurizio Bufalini Hospital  Cesena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Maira","sequence":"additional","affiliation":[{"name":"Neurology Department Guzzardi Hospital  Vittoria Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio","family":"Villani","sequence":"additional","affiliation":[{"name":"Neurophysiology Unit IRCCs Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2563-5830","authenticated-orcid":false,"given":"Pietro","family":"Mattioli","sequence":"additional","affiliation":[{"name":"Neurophysiology Unit IRCCs Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Franciotta","sequence":"additional","affiliation":[{"name":"Department of Laboratories UOM Unit\u00e0 Operativa Multizonale Laboratory of Clinical Pathology APSS Azienda Provinciale Servizi Sanitari Santa Chiara Hospital  Trento Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-215X","authenticated-orcid":false,"given":"Andrea","family":"Stabile","sequence":"additional","affiliation":[{"name":"Epilepsy Unit Fondazione IRCCs Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico \u201cCarlo Besta\u201d  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7443-6737","authenticated-orcid":false,"given":"Marco","family":"de Curtis","sequence":"additional","affiliation":[{"name":"Epilepsy Unit Fondazione IRCCs Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico \u201cCarlo Besta\u201d  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Gastaldi","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit Fondazione IRCCs Istituto di Ricovero e Cura a Carattere Scientifico Mondino  Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0808-3042","authenticated-orcid":false,"given":"Francesco","family":"Deleo","sequence":"additional","affiliation":[{"name":"Epilepsy Unit Fondazione IRCCs Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico \u201cCarlo Besta\u201d  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2741-4452","authenticated-orcid":false,"given":"Laura","family":"Librizzi","sequence":"additional","affiliation":[{"name":"Epilepsy Unit Fondazione IRCCs Istituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico \u201cCarlo Besta\u201d  Milan 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