Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis

ABSTRACT Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases sug...

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Autores principales:	Nischay Mishra, Terry Fei Fan Ng, Rachel L. Marine, Komal Jain, James Ng, Riddhi Thakkar, Adrian Caciula, Adam Price, Joel A. Garcia, Jane C. Burns, Kiran T. Thakur, Kimbell L. Hetzler, Janell A. Routh, Jennifer L. Konopka-Anstadt, W. Allan Nix, Rafal Tokarz, Thomas Briese, M. Steven Oberste, W. Ian Lipkin
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	VirCapSeq-VERT acute flaccid myelitis antibodies enterovirus enterovirus D-68 peptide array Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/aac3bce73c744aba9b817e8d6ed19651
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spelling	oai:doaj.org-article:aac3bce73c744aba9b817e8d6ed196512021-11-15T16:22:10ZAntibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis10.1128/mBio.01903-192150-7511https://doaj.org/article/aac3bce73c744aba9b817e8d6ed196512019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01903-19https://doaj.org/toc/2150-7511ABSTRACT Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) (P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively). IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease.Nischay MishraTerry Fei Fan NgRachel L. MarineKomal JainJames NgRiddhi ThakkarAdrian CaciulaAdam PriceJoel A. GarciaJane C. BurnsKiran T. ThakurKimbell L. HetzlerJanell A. RouthJennifer L. Konopka-AnstadtW. Allan NixRafal TokarzThomas BrieseM. Steven ObersteW. Ian LipkinAmerican Society for MicrobiologyarticleVirCapSeq-VERTacute flaccid myelitisantibodiesenterovirusenterovirus D-68peptide arrayMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	VirCapSeq-VERT acute flaccid myelitis antibodies enterovirus enterovirus D-68 peptide array Microbiology QR1-502
spellingShingle	VirCapSeq-VERT acute flaccid myelitis antibodies enterovirus enterovirus D-68 peptide array Microbiology QR1-502 Nischay Mishra Terry Fei Fan Ng Rachel L. Marine Komal Jain James Ng Riddhi Thakkar Adrian Caciula Adam Price Joel A. Garcia Jane C. Burns Kiran T. Thakur Kimbell L. Hetzler Janell A. Routh Jennifer L. Konopka-Anstadt W. Allan Nix Rafal Tokarz Thomas Briese M. Steven Oberste W. Ian Lipkin Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis
description	ABSTRACT Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) (P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively). IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease.
format	article
author	Nischay Mishra Terry Fei Fan Ng Rachel L. Marine Komal Jain James Ng Riddhi Thakkar Adrian Caciula Adam Price Joel A. Garcia Jane C. Burns Kiran T. Thakur Kimbell L. Hetzler Janell A. Routh Jennifer L. Konopka-Anstadt W. Allan Nix Rafal Tokarz Thomas Briese M. Steven Oberste W. Ian Lipkin
author_facet	Nischay Mishra Terry Fei Fan Ng Rachel L. Marine Komal Jain James Ng Riddhi Thakkar Adrian Caciula Adam Price Joel A. Garcia Jane C. Burns Kiran T. Thakur Kimbell L. Hetzler Janell A. Routh Jennifer L. Konopka-Anstadt W. Allan Nix Rafal Tokarz Thomas Briese M. Steven Oberste W. Ian Lipkin
author_sort	Nischay Mishra
title	Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis
title_short	Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis
title_full	Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis
title_fullStr	Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis
title_full_unstemmed	Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis
title_sort	antibodies to enteroviruses in cerebrospinal fluid of patients with acute flaccid myelitis
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/aac3bce73c744aba9b817e8d6ed19651
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Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis

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