Anti-RGS8 paraneoplastic cerebellar ataxia is preferentially associated with a particular subtype of Hodgkin’s lymphoma
Ataxia with anti-regulator of G-protein signaling 8 autoantibodies (RGS8-Abs) is an autoimmune disease recently described in four patients. 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.
Authors
- Samuel J. Pleasure (ORCID: https://orcid.org/0000-0001-8599-1613)
- Kelsey C. Zorn (ORCID: https://orcid.org/0000-0003-1227-2137)
- Antonio Farina (ORCID: https://orcid.org/0000-0002-5551-0185)
- John V. Pluvinage (ORCID: https://orcid.org/0000-0002-9607-2783)
- Virginie Desestret (ORCID: https://orcid.org/0000-0001-9643-1558)
- Thomas Ngo (ORCID: https://orcid.org/0000-0003-2504-1872)
- Jimmy Perrot (ORCID: https://orcid.org/0009-0008-4359-129X)
- Elise Peter (ORCID: https://orcid.org/0000-0002-7898-8069)
- Michael R. Wilson (ORCID: https://orcid.org/0000-0002-8705-5084)
- Christine Tranchant (ORCID: https://orcid.org/0000-0002-2895-1292)
- Le Duy (ORCID: https://orcid.org/0000-0001-7664-533X)
- Valérie Dubois (ORCID: https://orcid.org/0000-0002-1169-7697)
- Joseph L. DeRisi (ORCID: https://orcid.org/0000-0002-4611-9205)
- Jeffrey Marc Gelfand (ORCID: https://orcid.org/0000-0002-5121-3319)
- Nicolás Lundahl Ciano-Petersen (ORCID: https://orcid.org/0000-0001-9555-4847)
- Macarena Villagrán‐García (ORCID: https://orcid.org/0000-0001-9236-2428)
- Ramona Miske (ORCID: https://orcid.org/0000-0002-9424-4676)
- Véronique Rogemond (ORCID: https://orcid.org/0000-0003-2098-920X)
- Jérôme Honnorat (ORCID: https://orcid.org/0000-0002-4721-5952)
- Christopher M. Bartley (ORCID: https://orcid.org/0000-0002-1391-4130)
- Jean‐Christophe Antoine (ORCID: https://orcid.org/0000-0003-4944-9362)
- Alexandra Traverse-Glehen
- Madeleine Scharf
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Lyon College (US)
- University of California, San Francisco (US)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- Regenerative NanoMedicine (FR)
- Hospices Civils de Lyon (FR)
- Euroimmun Medizinische Labordiagnostika (Germany) (DE)
- Hôpital Lyon Sud (FR)
- Chan Zuckerberg Initiative (United States) (US)
- Établissement Français du Sang (FR)
- Centre Hospitalier Universitaire de Saint-Étienne (FR)
- Hôpital d'Hautepierre (FR)
- Instituto de Investigación Biomédica de Málaga (ES)
- Université de Strasbourg (FR)
- Université Jean Monnet (FR)
Publication Details
- Journal
- Journal of Neurology
- Published
- 2024-08-29
- DOI
- https://doi.org/10.1007/s00415-024-12618-4
- Citations
- 4
- Primary Topic
- Autoimmune Neurological Disorders and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.48
Funders
- Brain Research Foundation
- National Institute of Mental Health and Neurosciences
- Agence Nationale de la Recherche
- Hospices Civils de Lyon
- National Institutes of Health
- University of California, San Francisco
- National Institute of Mental Health