具有 G 蛋白信号传导抗调节剂 8 自身抗体 (RGS8-Abs) 的共济失调是最近在四名患者中描述的一种自身免疫性疾病。本研究旨在识别其他携带 RGS8-Ab 的患者，描述他们的临床特征，包括 RGS8 相关的自身免疫性小脑性共济失调 (ACA) 与癌症之间的联系。在法国副肿瘤神经综合征参考中心和加州大学旧金山脑炎和脑膜炎中心的生物保藏中回顾性鉴定了携带 RGS8-Ab 的患者。收集临床数据，并检索脑脊液、血清和肿瘤病理样本，以表征自身抗体和相关恶性肿瘤。仅鉴定出三名具有 RGS8-Ab 的患者。他们均表现为轻度至重度的纯小脑性共济失调，对当前的 ACA 免疫治疗方案无反应。两名患者患有罕见的特定亚型霍奇金淋巴瘤，称为结节性淋巴细胞为主的霍奇金淋巴瘤，具有非常轻微的扩散。在所有患者中检测到的自身抗体都富集了 RGS8 蛋白上的相同表位，RGS8 蛋白是一种在浦肯野细胞中生理表达的细胞内蛋白，但也在 RGS8 相关 ACA 患者的淋巴瘤细胞中特异性异位表达。目前的结果和之前描述的四个病例的结果表明，RGS8-Abs 定义了一种极其罕见的新的副肿瘤性神经系统综合征，主要见于中年男性，该综合征与纯小脑性共济失调和特异性表达 RGS8 抗原的特定淋巴瘤有关。与其他具有细胞内抗原的副肿瘤 ACA 一样，病程很严重，患者往往对免疫治疗反应不佳。© 2024。作者。

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.© 2024. The Author(s).