Detection of intrathecal antibodies to diagnose enterovirus infections of the central nervous system

Syriam Sooksawasdi Na Ayudhya, Gregorius J. Sips, Susanne Bogers, Lonneke M. E. Leijten, Brigitta M. Laksono, Leonard C. Smeets, Andrea Bruning, Kimberley Benschop, Katja Wolthers, Debby van Riel, Corine H. GeurtsvanKessel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Study design
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.
Original languageEnglish
Article number105190
JournalJournal of Clinical Virology
Publication statusPublished - Jul 2022

Bibliographical note

Funding Information:
DvR is supported by a fellowship from the Netherlands Organization for Scientific.Research (VIDI contract 91718308).

Publisher Copyright:
© 2022 The Author(s)


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