中文摘要：自身免疫抗体组的发展提高了对大脑和脊髓副肿瘤性神经系统疾病（PND）的诊断。本文报告了一例乳腺癌病史的女性患者，其表现为亚急性感觉共济失调，病程超过18个月。其检查和诊断结果与脊髓病一致。代谢、感染和自身免疫试验均为非诊断性试验。但因其对经验性免疫抑制有反应，促使进行进一步的自体免疫病因检查。利用噬菌体展示免疫沉淀测序（PhIP-Seq）进行无偏自身抗体筛查，鉴定了抗Yo抗原小脑变性相关蛋白2样（CDR2L）和CDR2的抗体，随后通过免疫印迹和细胞过表达检测进行验证。此外，CDR2L蛋白表达仅限于患者乳腺组织中表达HER2的肿瘤细胞。最近研究表明，CDR2L可能是抗Yo副肿瘤性小脑变性的主要抗原，但抗Yo脊髓病的特征性较差。通过免疫染色，检测了小鼠和人脊髓神经元CDR2L蛋白的表达。该病例证明了无偏检测在疑似PND患者中的诊断价值，支持了先前的观察结果，即抗Yo PND可能与孤立性脊髓病相关，并暗示CDR2L是脊髓中的潜在抗原。
外文摘要：The development of autoimmune antibody panels has improved the diagnosis of paraneoplastic neurological disorders (PNDs) of the brain and spinal cord. Here, we present a case of a woman with a history of breast cancer who presented with a subacute sensory ataxia that progressed over 18 months. Her examination and diagnostic studies were consistent with a myelopathy. Metabolic, infectious, and autoimmune testing were non-diagnostic. However, she responded to empirical immunosuppression, prompting further workup for an autoimmune etiology. An unbiased autoantibody screen utilizing phage display immunoprecipitation sequencing (PhIP-Seq) identified antibodies to the anti-Yo antigens cerebellar degeneration related protein 2 like (CDR2L) and CDR2, which were subsequently validated by immunoblot and cell-based overexpression assays. Furthermore, CDR2L protein expression was restricted to HER2 expressing tumor cells in the patient's breast tissue. Recent evidence suggests that CDR2L is likely the primary antigen in anti-Yo paraneoplastic cerebellar degeneration, but anti-Yo myelopathy is poorly characterized. By immunostaining, we detected neuronal CDR2L protein expression in the murine and human spinal cord. This case demonstrates the diagnostic utility of unbiased assays in patients with suspected PNDs, supports prior observations that anti-Yo PND can be associated with isolated myelopathy, and implicates CDR2L as a potential antigen in the spinal cord.
外文关键词：paraneoplastic neurologic disease；myelopathy；anti-Yo antibodies；phage display；breast cancer；CDR2L
作者：Bartley, CM；Parikshak, NN；Ngo, TT；Alexander, JA；Zorn, KC；Alvarenga, BA；Kang, MK；Pedriali, M；Pleasure, SJ；Wilson, MR
作者单位：Univ Calif San Francisco；Azienda Osped Univ
期刊名称：FRONTIERS IN NEUROLOGY
期刊影响因子：2.889
出版年份：2021
出版刊次：
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