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The present study aimed to identify other patients with RGS8-Abs, describe their clinical features, including the link between RGS8-related autoimmune cerebellar ataxia (ACA) and cancer. Patients with RGS8-Abs were identified retrospectively in the biological collections of the French Reference Center for Paraneoplastic Neurological Syndrome and the University of California San Francisco Center for Encephalitis and Meningitis. Clinical data were collected, and cerebrospinal fluid, serum, and tumor pathological samples were retrieved to characterize the autoantibodies and the associated malignancies. Only three patients with RGS8-Abs were identified. All of them presented with a pure cerebellar ataxia of mild to severe course, unresponsive to current immunotherapy regimens for ACA. Two patients presented with a Hodgkin lymphoma of the rare specific subtype called nodular lymphocyte-predominant Hodgkin lymphoma, with very mild extension. Autoantibodies detected in all patients enriched the same epitope on the RGS8 protein, which is an intracellular protein physiologically expressed in Purkinje cells but also ectopically expressed specifically in lymphoma cells of patients with RGS8-related ACA. The present results and those of the four cases previously described suggest that RGS8-Abs define a new paraneoplastic neurological syndrome of extreme rarity found mostly in middle-aged males that associates pure cerebellar ataxia and a particular lymphoma specifically expressing the RGS8 antigen. As in other paraneoplastic ACA with intracellular antigen, the disease course is severe, and patients tend to exhibit a poor response to immune therapy.<\/jats:p>","DOI":"10.1007\/s00415-024-12618-4","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T06:02:37Z","timestamp":1724911357000},"page":"6839-6846","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Anti-RGS8 paraneoplastic cerebellar ataxia is preferentially associated with a particular subtype of Hodgkin\u2019s lymphoma"],"prefix":"10.1007","volume":"271","author":[{"given":"Elise","family":"Peter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas Lundahl","family":"Ciano-Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le-Duy","family":"Do","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy","family":"Perrot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ngo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Pluvinage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Bartley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey C.","family":"Zorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"Miske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Scharf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena","family":"Villagr\u00e1n-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Farina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Rogemond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Antoine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Tranchant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Dubois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L.","family":"DeRisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel J.","family":"Pleasure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Gelfand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Traverse-Glehen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Honnorat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Desestret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"12618_CR1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000987","volume":"8","author":"R Miske","year":"2021","unstructured":"Miske R, Scharf M, Stark P et al (2021) Autoantibodies against the purkinje cell protein RGS8 in paraneoplastic cerebellar syndrome. 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J.L.D. and M.R.W. report being founders and paid consultants for Delve Bio, Inc., and they also receive licensing fees from CDI Labs. J.L.D. is a paid consultant for the Public Health Company and Allen & Co. M.R.W. receives unrelated research grant funding from Roche\/Genentech and Novartis, and received speaking honoraria from Genentech, Takeda, WebMD, and Novartis. J. M. G. has received research support to his institution from Hoffman LaRoche for clinical trials and serves on trial steering committees for Hoffman LaRoche; research support to his institution from Vigil Neurosciences for clinical trials; and personal fees for consulting from Arialys and Ventyx Biosciences. CMB is a physician consultant for the Neuroimmune Foundation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The study is part of the project Gene PNS (NCT03963700) and was approved by the Institutional Review Boards of the Hospices Civils de Lyon and UCSF (13\u201312,236).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"A written informed consent for sample analysis, medical research, and case publication was previously obtained from all patients.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}