Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands; Reinier Haga Medisch Diagnostisch Centrum, Delft, the Netherlands.
J Clin Virol. 2022 Jul;152:105190. doi: 10.1016/j.jcv.2022.105190. Epub 2022 May 23.
Enterovirus-D68 (EV-D68) predominantly causes respiratory disease. However, EV-D68 infections also have been associated with central nervous system (CNS) complications, most specifically acute flaccid myelitis (AFM). Diagnosing EV-D68-associated CNS disease is challenging since viral RNA is rarely detected in cerebrospinal fluid (CSF).
In order to determine an EV antibody index (AI), we evaluated the value of a commercially available quantitative ELISA to detect EV-specific antibodies in paired CSF and blood.
Nine paired CSF and blood samples were obtained from patients with EV-D68-associated AFM or from patients with a confirmed EV-associated CNS disease. EV-specific antibodies were detected using a quantitative ELISA. A Reiber diagram analysis was performed, by which the AI was calculated. Subsequently, EV ELISA results were compared with an EV-D68 virus neutralization test.
ELISA detected EV-specific antibodies in 1 out of the 3 patients with EV-D68-associated AFM and in 3 out of the 6 patients with confirmed EV-associated CNS disease. In these patients, the AI was indicative for intrathecal antibody production against enterovirus. Assay comparison showed that EV-D68 neutralizing antibody detection increased the sensitivity of EV-D68 antibody detection.
A quantitative EV IgG ELISA in combination with Reiber diagram analysis and AI-calculation can be used as a diagnostic tool for EV-associated CNS disease, including EV-D68. An EV-D68 specific ELISA will improve the sensitivity of the tool. With the growing awareness that the detection of non-polio enteroviruses needs to be improved, diagnostic laboratories should consider implementation of EV serology.
肠道病毒 D68（EV-D68）主要引起呼吸道疾病。然而，EV-D68 感染也与中枢神经系统（CNS）并发症有关，最常见的是急性弛缓性脊髓炎（AFM）。由于病毒 RNA 在脑脊液（CSF）中很少被检测到，因此诊断 EV-D68 相关 CNS 疾病具有挑战性。
为了确定 EV 抗体指数（AI），我们评估了一种商业上可用的定量 ELISA 检测配对 CSF 和血液中 EV 特异性抗体的价值。
从 EV-D68 相关 AFM 患者或已确诊的 EV 相关 CNS 疾病患者中获得 9 对 CSF 和血液样本。使用定量 ELISA 检测 EV 特异性抗体。进行 Reiber 图分析，计算 AI。随后，将 EV ELISA 结果与 EV-D68 病毒中和试验进行比较。
ELISA 在 3 例 EV-D68 相关 AFM 患者中的 1 例和 6 例已确诊的 EV 相关 CNS 疾病患者中的 3 例中检测到 EV 特异性抗体。在这些患者中，AI 提示针对肠道病毒的鞘内抗体产生。检测比较表明，EV-D68 中和抗体检测提高了 EV-D68 抗体检测的敏感性。
定量 EV IgG ELISA 结合 Reiber 图分析和 AI 计算可作为 EV 相关 CNS 疾病（包括 EV-D68）的诊断工具。EV-D68 特异性 ELISA 将提高该工具的敏感性。随着人们越来越意识到需要改进非脊髓灰质炎肠道病毒的检测，诊断实验室应考虑实施 EV 血清学检测。
