TY - JOUR
T1 - Detection of intrathecal antibodies to diagnose enterovirus infections of the central nervous system
AU - Sooksawasdi Na Ayudhya, Syriam
AU - Sips, Gregorius J.
AU - Bogers, Susanne
AU - Leijten, Lonneke M. E.
AU - Laksono, Brigitta M.
AU - Smeets, Leonard C.
AU - Bruning, Andrea
AU - Benschop, Kimberley
AU - Wolthers, Katja
AU - van Riel, Debby
AU - GeurtsvanKessel, Corine H.
N1 - Funding Information: DvR is supported by a fellowship from the Netherlands Organization for Scientific.Research (VIDI contract 91718308). Publisher Copyright: © 2022 The Author(s)
PY - 2022/7/1
Y1 - 2022/7/1
N2 - Background: 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). Objective: 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. Results: 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. Conclusions: 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.
AB - Background: 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). Objective: 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. Results: 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. Conclusions: 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.
KW - Acute flaccid myelitis
KW - Antibody index
KW - Enterovirus D68
KW - Enteroviruses
KW - Reiber diagram
KW - Serology
UR - http://www.scopus.com/inward/record.url?scp=85131100778&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jcv.2022.105190
DO - https://doi.org/10.1016/j.jcv.2022.105190
M3 - Article
C2 - 35640402
SN - 1386-6532
VL - 152
JO - Journal of clinical virology
JF - Journal of clinical virology
M1 - 105190
ER -