From the Institute for Experimental Immunology (R.M., M.S., A.O., Y.D., N.R., C.P., L.K.), Affiliated to EUROIMMUN Medizinische Labordiagnostika AG, Luebeck; Department of Neurology (P.S., H.D.), Krankenhaus St. Elisabeth, Damme; Laboratory Krone (C.I.B.), Bad Salzuflen; Department of Neurology (C.B., P.K.), Nordwest-Krankenhaus Sanderbusch, Sande; Clinical Immunological Laboratory Prof. Dr. Med. Winfried Stöcker (K.B., B.T.), Luebeck; and Department of Neurology (C.F.), Charité - Universitätsmedizin Berlin, Berlin, Germany.
Neurol Neuroimmunol Neuroinflamm. 2021 Mar 29;8(3). doi: 10.1212/NXI.0000000000000987. Print 2021 May.
To describe the identification of regulator of G-protein signaling 8 (RGS8) as an autoantibody target in patients with cerebellar syndrome associated with lymphoma.
Sera of 4 patients with a very similar unclassified reactivity against cerebellar Purkinje cells were used in antigen identification experiments. Immunoprecipitations with cerebellar lysates followed by mass spectrometry identified the autoantigen, which was verified by recombinant immunofluorescence assay, immunoblot, and ELISA with the recombinant protein.
The sera and CSF of 4 patients stained the Purkinje cells and molecular layer of the cerebellum. RGS8 was identified as the target antigen in all 4 sera. In a neutralization experiment, recombinant human RGS8 was able to neutralize the autoantibodies' tissue reaction. Patient sera and CSF showed a specific reactivity against recombinant RGS8 in ELISA and immunoblot, whereas no such reactivity was detectable in the controls. Clinical data were available for 2 of the 4 patients, remarkably both presented with cerebellar syndrome accompanied by B-cell lymphoma of the stomach (patient 1, 53 years) or Hodgkin lymphoma (patient 2, 74 years).
Our results indicate that autoantibodies against the intracellular Purkinje cell protein RGS8 represent new markers for paraneoplastic cerebellar syndrome associated with lymphoma.
This study provided Class IV evidence that autoantibodies against the intracellular Purkinje cell protein RGS8 are associated with paraneoplastic cerebellar syndrome in lymphoma.
描述 G 蛋白信号转导调节因子 8（RGS8）作为与淋巴瘤相关小脑综合征患者自身抗体靶标的鉴定。
使用 4 例具有非常相似的未分类针对小脑浦肯野细胞反应性的血清进行抗原鉴定实验。用小脑裂解物进行免疫沉淀，然后进行质谱分析，鉴定自身抗原，并用重组免疫荧光分析、免疫印迹和重组蛋白 ELISA 进行验证。
4 例患者的血清和 CSF 均染色了小脑浦肯野细胞和小脑分子层。RGS8 被鉴定为 4 例血清中的靶抗原。在中和实验中，重组人 RGS8 能够中和自身抗体的组织反应。患者血清和 CSF 在 ELISA 和免疫印迹中显示出针对重组 RGS8 的特异性反应，而对照组则未检测到这种反应。4 例患者中有 2 例的临床数据可用，均表现为伴有胃 B 细胞淋巴瘤（患者 1，53 岁）或霍奇金淋巴瘤（患者 2，74 岁）的小脑综合征。
我们的结果表明，针对细胞内浦肯野细胞蛋白 RGS8 的自身抗体是与淋巴瘤相关的副肿瘤性小脑综合征的新标志物。
本研究提供了 IV 级证据，表明针对细胞内浦肯野细胞蛋白 RGS8 的自身抗体与淋巴瘤相关的副肿瘤性小脑综合征有关。
