From the Department of Neurology (I.H., M.H., C.T., C.V.), Haukeland University Hospital; Department of Clinical Medicine (I.H., K.M., C.V.), University of Bergen; and Departments of Neurology and Clinical Medicine (I.H., C.T., C.V.), Neuro-SysMed-Centre of Excellence for Experimental Therapy in Neurology, Bergen, Norway.
Neurol Neuroimmunol Neuroinflamm. 2021 Feb 2;8(2). doi: 10.1212/NXI.0000000000000963. Print 2021 Mar.
Investigate the value of including cerebellar degeneration-related protein 2-like (CDR2L) as a marker in commercial diagnostic tests for anti-Yo-associated paraneoplastic cerebellar degeneration (PCD).
We included sera and CSF samples from 24 patients with suspected PCD (6 of whom had PCD with underlying gynecologic or breast cancer), who were positive for Yo antibodies using the commercially available, paraneoplastic neurologic syndromes (PNS) 14 Line Assay from Ravo Diagnostika. The samples were further evaluated using the EUROLINE PNS 12 Ag Line Assay and a cell-based assay (CBA) from Euroimmun. For confirmation of positive lineblot results, we used indirect immunofluorescence of rat cerebellar sections. We also tested all samples in 2 assays developed in-house: a CBA for CDR2L and a Western blot analysis using recombinant cerebellar degeneration-related protein 2 (CDR2) and CDR2L proteins.
In PNS 14 and PNS 12 Ag Line Assays, anti-CDR2 reactivity was observed for 24 (100%) and 20 (83%) of the 24 samples, respectively. Thirteen of 24 subjects (54%) were also positive using the Euroimmun CBA. Rat cerebellar immunofluorescence was the best confirmatory test. In our in-house CBA for CDR2L and Western blot for CDR2 and CDR2L, only the 6 patients with confirmed PCD reacted with CDR2L.
Commercially available tests for Yo antibody detection have low specificity for PCD because these assays use CDR2 as antigen. By adding a test for CDR2L, which is the major Yo antigen, the accuracy of PCD diagnosis greatly improved.
This study provides Class III evidence that a CBA for CDR2L accurately identifies patients with PCD.
研究将小脑退行性变相关蛋白 2 样蛋白（CDR2L）作为抗 Yo 相关副肿瘤性小脑变性（PCD）商业诊断检测标志物的价值。
我们纳入了 24 例疑似 PCD 患者（其中 6 例为伴发妇科或乳腺癌的 PCD）的血清和脑脊液样本，这些患者的 Yo 抗体均为阳性，采用的是 Ravo Diagnostika 的商业化的副肿瘤神经综合征（PNS）14 线检测。使用 EUROLINE PNS 12 Ag 线检测和 Euroimmun 的细胞基础检测（CBA）进一步评估这些样本。为了确认阳性线印迹结果，我们使用了大鼠小脑切片的间接免疫荧光。我们还使用内部开发的 2 种检测方法测试了所有样本：一种是针对 CDR2L 的 CBA，另一种是使用重组小脑退行性变相关蛋白 2（CDR2）和 CDR2L 蛋白的 Western blot 分析。
在 PNS 14 和 PNS 12 Ag 线检测中，分别有 24 个（100%）和 20 个（83%）样本对抗 CDR2 有反应。13 名（54%）24 名受试者使用 Euroimmun CBA 也为阳性。大鼠小脑免疫荧光是最佳的确认性检测。在我们内部针对 CDR2L 的 CBA 和针对 CDR2 和 CDR2L 的 Western blot 中，只有 6 名确诊 PCD 的患者与 CDR2L 反应。
用于检测 Yo 抗体的商业化检测方法对 PCD 的特异性较低，因为这些检测使用 CDR2 作为抗原。通过添加针对主要 Yo 抗原 CDR2L 的检测，PCD 诊断的准确性大大提高。
本研究提供了 III 级证据，表明针对 CDR2L 的 CBA 可准确识别 PCD 患者。
