Anti-RGS8 paraneoplastic cerebellar ataxia is preferentially associated with a particular subtype of Hodgkin's lymphoma.

in Journal of neurology by Elise Peter, Nicolas Lundahl Ciano-Petersen, Le-Duy Do, Jimmy Perrot, Thomas Ngo, John Pluvinage, Christopher M Bartley, Kelsey C Zorn, Ramona Miske, Madeleine Scharf, Macarena Villagrán-García, Antonio Farina, Véronique Rogemond, Jean-Christophe Antoine, Christine Tranchant, Valérie Dubois, Joseph L DeRisi, Samuel J Pleasure, Michael R Wilson, Jeffrey M Gelfand, Alexandra Traverse-Glehen, Jérôme Honnorat, Virginie Desestret

TLDR

  • The study found that some people have a disease called RGS8-Abs, which is a type of autoimmune disease that causes a rare type of cancer called nodular lymphocyte-predominant Hodgkin lymphoma. The study found that people with RGS8-Abs have a disease called cerebellar ataxia, which is a type of paralysis that affects the cerebellum. The study also found that people with RGS8-Abs have a particular type of cancer that expresses a protein called RGS8. The study suggests that RGS8-Abs define a new type of paraneoplastic neurological syndrome that is extremely rare and found mostly in middle-aged males. The study found that people with RGS8-Abs have a disease called cerebellar ataxia, which is a type of paralysis that affects the cerebellum. The study also found that people with RGS8-Abs have a particular type of cancer that expresses a protein called RGS8. The study suggests that RGS8-Abs define a new type of paraneoplastic neurological syndrome that is extremely rare and found mostly in middle-aged males.

Abstract

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.

Overview

  • The study aims to identify other patients with RGS8-Abs, describe their clinical features, and link RGS8-related autoimmune cerebellar ataxia (ACA) to cancer. The study identifies three patients with RGS8-Abs, all of whom presented with a pure cerebellar ataxia of mild to severe course, unresponsive to current immunotherapy regimens for ACA. Two patients had 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 study suggests 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. The study's primary objective is to identify other patients with RGS8-Abs and describe their clinical features, link RGS8-related autoimmune cerebellar ataxia (ACA) to cancer, and 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.

Comparative Analysis & Findings

  • The study identifies three patients with RGS8-Abs, all of whom presented with a pure cerebellar ataxia of mild to severe course, unresponsive to current immunotherapy regimens for ACA. Two patients had 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 study suggests 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.

Implications and Future Directions

  • The study's findings 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. The study identifies three patients with RGS8-Abs, all of whom presented with a pure cerebellar ataxia of mild to severe course, unresponsive to current immunotherapy regimens for ACA. The study's primary objective is to identify other patients with RGS8-Abs and describe their clinical features, link RGS8-related autoimmune cerebellar ataxia (ACA) to cancer, and 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. The study's findings 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. The study identifies three patients with RGS8-Abs, all of whom presented with a pure cerebellar ataxia of mild to severe course, unresponsive to current immunotherapy regimens for ACA. The study's primary objective is to identify other patients with RGS8-Abs and describe their clinical features, link RGS8-related autoimmune cerebellar ataxia (ACA) to cancer, and 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. The study's findings 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. The study identifies three patients with RGS8-Abs, all of whom presented with a pure cerebellar ataxia of mild to severe course, unresponsive to current immunotherapy regimens for ACA. The study's primary objective is to identify other patients with RGS8-Abs and describe their clinical features, link RGS8-related autoimmune cerebellar ataxia (ACA) to cancer, and 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.
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