βIV- spectrin 自身抗体在 2 例可能副肿瘤性起源的神经病变患者中的：病例系列研究。
βIV-Spectrin Autoantibodies in 2 Individuals With Neuropathy of Possible Paraneoplastic Origin: A Case Series.
机构信息
From the Weill Institute for Neurosciences (C.M.B., T.T.N., B.D.A., M.R.W., S.J. Pleasure), Department of Psychiatry and Behavioral Sciences (C.M.B., T.T.N.), Department of Neurology (B.D.A., M.R.W., S.J. Pleasure), UCSF School of Medicine (A.F.K.), University of California, San Francisco; Department of Neuroscience (L.H.T., M.N.R.), Baylor College of Medicine, Houston, TX; Department of Neurology (M.S.), University of California, Irvine; Chan Zuckerberg Biohub (J.L.D.), San Francisco, CA; Department of Biochemistry and Biophysics (J.L.D.), University of California, San Francisco; Department of Laboratory Medicine and Pathology (S.J. Pittock, D.D.), Department of Neurology (S.J. Pittock, D.D.), andCenter MS and Autoimmune Neurology (S.J. Pittock, D.D.), Mayo Clinic, Rochester, MN.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2022 May 17;9(4). doi: 10.1212/NXI.0000000000001188. Print 2022 Jul.
OBJECTIVE
To identify the autoantigen in 2 individuals with possible seronegative paraneoplastic neuropathy.
METHODS
Serum and CSF were screened by tissue-based assay and panned for candidate autoantibodies by phage display immunoprecipitation sequencing (PhIP-Seq). The candidate antigen was validated by immunostaining knockout tissue and HEK 293T cell-based assay.
RESULTS
Case 1 presented with gait instability, distal lower extremity numbness, and paresthesias after a recent diagnosis of serous uterine and fallopian carcinoma. Case 2 had a remote history of breast adenocarcinoma and presented with gait instability, distal lower extremity numbness, and paresthesias that progressed to generalized weakness. CSF and serum from both patients immunostained the axon initial segment (AIS) and node of Ranvier (NoR) of mice and enriched βIV-spectrin by PhIP-Seq. Patient CSF and serum failed to immunostain NoRs in dorsal root sensory neurons from βI/βIV-deficient mice. βIV-spectrin autoantibodies were confirmed by overexpression of AIS and nodal βIV-spectrin isoforms Σ1 and Σ6 by a cell-based assay. βIV-spectrin was not enriched in a combined 4,815 PhIP-Seq screens of healthy and other neurologic disease patients.
DISCUSSION
Therefore, βIV-spectrin autoantibodies may be a marker of paraneoplastic neuropathy.
CLASSIFICATION OF EVIDENCE
This study provides Class IV evidence that βIV-spectrin antibodies are specific autoantibody biomarkers for paraneoplastic neuropathy.
目的
鉴定 2 例可能为血清阴性副肿瘤性神经病患者的自身抗原。
方法
通过组织基检测法筛选血清和脑脊液，并通过噬菌体展示免疫沉淀测序（PhIP-Seq）对候选自身抗体进行淘选。通过免疫染色敲除组织和基于 HEK 293T 细胞的测定验证候选抗原。
结果
例 1 在诊断出浆液性子宫和输卵管癌后出现步态不稳、远端下肢麻木和感觉异常。例 2 有远处乳腺癌病史，出现步态不稳、远端下肢麻木和感觉异常，进而发展为全身无力。来自这 2 位患者的 CSF 和血清免疫染色了小鼠的轴突起始段（AIS）和郎飞结（NoR），并通过 PhIP-Seq 富集了βIV- spectrin。患者 CSF 和血清未能免疫染色缺乏βI/βIV 的小鼠背根感觉神经元的 NoRs。通过细胞测定证实了βIV-spectrin 自身抗体的存在，该测定导致 AIS 和节段性βIV-spectrin 异构体 Σ1 和 Σ6 的过表达。βIV-spectrin 在健康人和其他神经疾病患者的 4815 次联合 PhIP-Seq 筛选中未被富集。
讨论
因此，βIV-spectrin 自身抗体可能是副肿瘤性神经病的标志物。
证据分类
本研究提供了 IV 级证据，表明βIV-spectrin 抗体是副肿瘤性神经病的特异性自身抗体生物标志物。
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