From the French Reference Center on Paraneoplastic Neurological Syndromes (B.D., S.M.-C., B.J., A.V., G.P., V.R., A.-L.P., V.D., J.H.), Hospices Civils de Lyon, Hôpital Neurologique; Synatac Team (B.D., S.M.-C., B.J., A.V., G.P., V.R., A.-L.P., V.D., J.H.), Institute NeuroMyoGène, INSERM U1217/CNRS UMR5310, Université Claude Bernard Lyon 1; and Department of Immunology (B.D., C.L., N.F.), Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Lyon, France.
Neurol Neuroimmunol Neuroinflamm. 2020 Mar 13;7(3). doi: 10.1212/NXI.0000000000000701. Print 2020 May.
To investigate the diagnostic yield of commercial immunodots to detect onconeural antibodies associated with paraneoplastic neurologic syndromes (PNSs), we analyzed the proportion of confirmed positive results using alternative techniques.
Sera (n = 5,300) of patients with suspected PNS were tested by PNS+2 blot (Ravo Diagnostika; January 2016-May 2017) or EUROLINE PNS 12 Ag (Euroimmun; July 2017-November 2018). Positive samples were further explored by in-house indirect immunofluorescence and a third in-house technique (Western blot or cell-based assay) using recombinant protein. Those found negative by these 2 techniques were considered as nonconfirmed. We analyzed the relationship between band intensity and final confirmation. Clinical data were collected for all confirmed results and nonconfirmed EUROLINE immunodots.
PNS+2 blot was positive in 128/1,658 (7.7%) sera and confirmed in 47/128 (36.7%). EUROLINE was positive in 186/3,626 (5.1%) and confirmed in 56/186 (30.1%). Confirmation was highly variable among the antibodies tested, from 7.2% (PNS+2 blot) and 5.8% (EUROLINE) for anti-Yo to 88.2% (PNS+2 blot) and 65.0% (EUROLINE) for anti-Hu. None of the 27 weak positive sera by EUROLINE was confirmed. Band intensity in confirmed cases was variable among the antibodies from strong positive for all anti-Yo (n = 3) and anti-Hu (n = 11) to positive (n = 19) or strong positive (n = 9) for anti-SOX1. Among patients with a nonconfirmed EUROLINE result and available clinical information, all had an alternative diagnosis, and only 6.7% had cancer.
Immunodots may be useful for PNS screening, but a threshold should be established for each antibody, and clinical information and confirmation by other techniques are essential.
The study provides Class IV evidence that immunodot assays for onconeural antibodies accurately identify patients with paraneoplastic neurologic syndromes.
通过分析使用替代技术确认阳性结果的比例，研究商业免疫斑点检测与副肿瘤神经综合征（PNS）相关的肿瘤相关抗体的诊断效能。
采用 PNS+2 印迹法（Ravo Diagnostika；2016 年 1 月至 2017 年 5 月）或 EUROLINE PNS 12 Ag（Euroimmun；2017 年 7 月至 2018 年 11 月）对疑似 PNS 患者的血清（n=5300）进行检测。使用重组蛋白对阳性样本进行进一步的内部间接免疫荧光和第三种内部技术（Western blot 或细胞测定）检测。这两种技术均为阴性的样本被认为是非确认性的。我们分析了条带强度与最终确认之间的关系。对所有确认结果和非确认性 EUROLINE 免疫斑点的临床数据进行了收集。
PNS+2 印迹法阳性 128/1658 例（7.7%），确认阳性 47/128 例（36.7%）。EUROLINE 阳性 186/3626 例（5.1%），确认阳性 56/186 例（30.1%）。抗体检测的确认结果差异较大，抗 Yo 为 7.2%（PNS+2 印迹法）和 5.8%（EUROLINE），抗 Hu 为 88.2%（PNS+2 印迹法）和 65.0%（EUROLINE）。EUROLINE 检测出的 27 例弱阳性血清均未被确认。确认病例的条带强度因抗体而异，抗 Yo（n=3）和抗 Hu（n=11）均为强阳性，抗 SOX1 为阳性（n=19）或强阳性（n=9）。在 EUROLINE 结果非确认且有可用临床信息的患者中，所有患者均有其他诊断，仅有 6.7%的患者患有癌症。
免疫斑点法可能对 PNS 筛查有用，但应针对每种抗体设定阈值，且临床信息和其他技术的确认必不可少。
本研究提供了 IV 级证据，表明肿瘤相关抗体的免疫斑点检测可准确识别副肿瘤神经综合征患者。
