{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:03:21Z","timestamp":1790651001072,"version":"4.1.0"},"reference-count":82,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T00:00:00Z","timestamp":1676246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin","award":["EXC-2049\u2014390688087"],"award-info":[{"award-number":["EXC-2049\u2014390688087"]}]},{"name":"Berlin Institute of Health","award":["EXC-2049\u2014390688087"],"award-info":[{"award-number":["EXC-2049\u2014390688087"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) under Germany\u2019s Excellence Strategy","doi-asserted-by":"publisher","award":["EXC-2049\u2014390688087"],"award-info":[{"award-number":["EXC-2049\u2014390688087"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Ophelia syndrome is characterized by the coincidence of severe neuropsychiatric symptoms, classical Hodgkin lymphoma, and the presence of antibodies to the metabotropic glutamate 5 receptor (mGluR5). Little is known about the pathogenetic link between these symptoms and the role that anti-mGluR5-antibodies play. We investigated lymphoma tissue from patients with Ophelia syndrome and with isolated classical Hodgkin lymphoma by quantitative immunocytochemistry for mGluR5-expression. Further, we studied the L-1236, L-428, L-540, SUP-HD1, KM-H2, and HDLM-2 classical Hodgkin lymphoma cell lines by FACS and Western blot for mGluR5-expression, and by transcriptome analysis. mGluR5 surface expression differed significantly in terms of receptor density, distribution pattern, and percentage of positive cells. The highest expression levels were found in the L-1236 line. RNA-sequencing revealed more than 800 genes that were higher expressed in the L-1236 line in comparison to the other classical Hodgkin lymphoma cell lines. High mGluR5-expression was associated with upregulation of PI3K\/AKT and MAPK pathways and of downstream targets (e.g., EGR1) known to be involved in classical Hodgkin lymphoma progression. Finally, mGluR5 expression was increased in the classical Hodgkin lymphoma-tissue of our Ophelia syndrome patient in contrast to five classical Hodgkin lymphoma-patients without autoimmune encephalitis. Given the association of encephalitis and classical Hodgkin lymphoma in Ophelia syndrome, it is possible that mGluR5-expression in classical Hodgkin lymphoma cells not only drives tumor progression but also triggers anti-mGluR5 encephalitis even before classical Hodgkin lymphoma becomes manifest.<\/jats:p>","DOI":"10.3390\/cells12040606","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T05:25:26Z","timestamp":1676265926000},"page":"606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hodgkin Lymphoma Cell Lines and Tissues Express mGluR5: A Potential Link to Ophelia Syndrome and Paraneoplastic Neurological Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Sofia","family":"Schnell","sequence":"first","affiliation":[{"name":"NeuroCure Cluster of Excellence, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Department of Neuropediatrics, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Knierim","sequence":"additional","affiliation":[{"name":"NeuroCure Cluster of Excellence, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Department of Neuropediatrics, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Center for Chronically Sick Children, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Bittigau","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Center for Chronically Sick Children, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2913-1015","authenticated-orcid":false,"given":"Jakob","family":"Kreye","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Center for Chronically Sick Children, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH), 10178 Berlin, Germany"},{"name":"Department of Neurology and Experimental Neurology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0590-3674","authenticated-orcid":false,"given":"Kathrin","family":"Hauptmann","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Hundsdoerfer","sequence":"additional","affiliation":[{"name":"Helios Klinikum Berlin-Buch, Kinder-und Jugendmedizin, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Morales-Gonzalez","sequence":"additional","affiliation":[{"name":"NeuroCure Cluster of Excellence, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Department of Neuropediatrics, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2824-3891","authenticated-orcid":false,"given":"Markus","family":"Schuelke","sequence":"additional","affiliation":[{"name":"NeuroCure Cluster of Excellence, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Department of Neuropediatrics, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Nikolaus","sequence":"additional","affiliation":[{"name":"NeuroCure Cluster of Excellence, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Department of Neuropediatrics, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Center for Chronically Sick Children, Charit\u00e9-Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"},{"name":"Berlin Institute of Health (BIH), 10178 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/s41375-021-01204-6","article-title":"Molecular Biology of Hodgkin 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