{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:52:07Z","timestamp":1761061927535,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Limbic encephalitis (LE) due to anti-leucine-rich glioma-inactivated 1 (LGI1) antibodies is an autoimmune disease characterized by distinct clinical features unique to LGI1 LE, such as faciobrachial dystonic seizures. However, it is unclear whether an additional disease-related LGI1 antigen-specific T cell response is involved in the pathogenesis of this disease. To address this question, we studied the effect of recombinant LGI1 on the proliferation and effector-specific cytokine production (IFN-\u03b3, IL-5, IL-10, and IL-17) of peripheral blood mononuclear cells (PBMCs) from patients with LGI1 LE and healthy controls. We observed that recombinant LGI1 stimulated the proliferation of PBMCs from patients with LGI1 LE, but not from healthy controls. Cytokine measurement of cell culture supernatants from PBMCs incubated with recombinant LGI1 revealed a highly significant increase in IL-10 release in PBMCs from patients with LGI1 LE in comparison with healthy controls. These results suggest that LGI1-mediated stimulation of PBMCs from patients with LGI1 LE leads to the establishment of an IL-10-dominated immunosuppressive cytokine milieu, which may inhibit Th1 differentiation and support B cell proliferation, IgG production, and IgG subclass switching.<\/jats:p>","DOI":"10.3390\/ijms25052581","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T04:31:23Z","timestamp":1708662683000},"page":"2581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Leucine-Rich Glioma-Inactivated 1 (LGI1) Protein Stimulates Proliferation and IL-10 Production in Peripheral Blood Mononuclear Cells of Patients with LGI1 Antibody-Mediated Autoimmune Encephalitis In Vitro"],"prefix":"10.3390","volume":"25","author":[{"given":"Alexander","family":"Goihl","sequence":"first","affiliation":[{"name":"Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6441-9631","authenticated-orcid":false,"given":"Dirk","family":"Reinhold","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"},{"name":"Health Campus Immunology, Infection and Inflammation (GC-I3), Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"},{"name":"ChaMP, Center for Health and Medical Prevention, Otto-von-Guericke-University, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annegret","family":"Reinhold","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"},{"name":"Health Campus Immunology, Infection and Inflammation (GC-I3), Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"},{"name":"ChaMP, Center for Health and Medical Prevention, Otto-von-Guericke-University, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4321-7405","authenticated-orcid":false,"given":"Burkhart","family":"Schraven","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"},{"name":"Health Campus Immunology, Infection and Inflammation (GC-I3), Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany"},{"name":"ChaMP, Center for Health and Medical Prevention, Otto-von-Guericke-University, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1262-6169","authenticated-orcid":false,"given":"Peter","family":"K\u00f6rtvelyessy","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE) Magdeburg, 39120 Magdeburg, Germany"},{"name":"Klinik und Hochschulambulanz f\u00fcr Neurologie, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt Universit\u00e4t zu Berlin, 10117 Berlin, Germany"},{"name":"Labor Berlin, Innovations, Sylter Strasse 2, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1212\/WNL.0000000000003009","article-title":"Anti-LGI1-associated cognitive impairment: Presentation and long-term outcome","volume":"87","author":"Sabater","year":"2016","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/ana.25131","article-title":"Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis","volume":"83","author":"Dubey","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1093\/brain\/awx323","article-title":"The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Faciobrachial Dystonic Seizures Study Group","volume":"141","author":"Thompson","year":"2018","journal-title":"Brain"},{"key":"ref_4","first-page":"3144","article-title":"LGI1 antibodies alter Kv1.1 and AMPA receptors changing synaptic excitability, plasticity and memory","volume":"141","author":"Sell","year":"2018","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1093\/brain\/awaa104","article-title":"Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms","volume":"143","author":"Ramberger","year":"2020","journal-title":"Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/ana.25666","article-title":"Human Cerebrospinal Fluid Monoclonal LGI1 Autoantibodies Increase Neuronal Excitability","volume":"87","author":"Kornau","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e2022580118","DOI":"10.1073\/pnas.2022580118","article-title":"LGI1-ADAM22-MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention","volume":"118","author":"Fukata","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1212\/WNL.0000000000003173","article-title":"Anti-LGI1 encephalitis: Clinical syndrome and long-term follow-up","volume":"87","author":"Thijs","year":"2016","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e669","DOI":"10.1212\/NXI.0000000000000669","article-title":"Intrathecal B-cell activation in LGI1 antibody encephalitis","volume":"7","author":"Irani","year":"2020","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.cyto.2015.10.001","article-title":"CSF cytokines\/chemokines as biomarkers in neuroinflammatory CNS disorders: A systematic review","volume":"77","author":"Kothur","year":"2016","journal-title":"Cytokine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1016\/S0140-6736(15)60361-0","article-title":"The active intrathecal B-cell response in LGI1-antibody encephalitis","volume":"385","author":"Irani","year":"2015","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"155226","DOI":"10.1016\/j.cyto.2020.155226","article-title":"Serum and CSF cytokine levels mirror different neuroimmunological mechanisms in patients with LGI1 and Caspr2 encephalitis","volume":"135","author":"Goihl","year":"2020","journal-title":"Cytokine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00401-009-0582-4","article-title":"Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma","volume":"118","author":"Zhou","year":"2009","journal-title":"Acta Neuropathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12974-016-0507-9","article-title":"Anti-N-methyl-D-aspartate receptor encephalitis: The clinical course in light of the chemokine and cytokine levels in cerebrospinal fluid","volume":"13","author":"Liba","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.jaci.2014.07.041","article-title":"IL-10-overexpressing B cells regulate innate and adaptive immune responses","volume":"135","author":"Stanic","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3555","DOI":"10.4049\/jimmunol.160.7.3555","article-title":"IgE versus IgG4 production can be differentially regulated by IL-10","volume":"160","author":"Jeannin","year":"1998","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4718","DOI":"10.4049\/jimmunol.174.8.4718","article-title":"T regulatory-1 cells induce IgG4 production by B cells: Role of IL-10","volume":"174","author":"Satoguina","year":"2005","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.brainres.2010.11.096","article-title":"IL-10 directly protects cortical neurons by activating PI-3 kinase and STAT-3 pathways","volume":"1373","author":"Sharma","year":"2011","journal-title":"Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1111\/j.1471-4159.2009.06263.x","article-title":"Interleukin-10 provides direct trophic support to neurons","volume":"110","author":"Zhou","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/eji.1830190602","article-title":"Interleukin 5 is a differentiation factor for IgA B cells","volume":"19","author":"Schoenbeck","year":"1989","journal-title":"Eur. J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jneuroim.2016.05.023","article-title":"Distinct intrathecal interleukin-17\/interleukin-6 activation in anti-N-methyl-d-aspartate receptor encephalitis","volume":"297","author":"Byun","year":"2016","journal-title":"J. Neuroimmunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"673021","DOI":"10.3389\/fimmu.2021.673021","article-title":"Cerebrospinal Fluid IL-17A Could Predict Acute Disease Severity in Non-NMDA-Receptor Autoimmune Encephalitis","volume":"12","author":"Levraut","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/0092-8674(78)90254-4","article-title":"Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor","volume":"14","author":"Wigler","year":"1978","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ludewig, S., Salzburger, L., Goihl, A., Rhone, J., Leypoldt, F., Bittner, D., D\u00fczel, E., Schraven, B., Reinhold, D., and Korte, M. (2023). Antibody properties associate with clinical phenotypes in LGI1 encephalitis. 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