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MBio. 2019 Aug 13;10(4). pii: e01903-19. doi: 10.1128/mBio.01903-19.

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

Author information

1
Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA.
2
Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
3
Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California, USA.
4
Division of Critical Care and Hospitalist Neurology, Department of Neurology, Columbia Irving University Medical Center, New York, New York, USA.
5
Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA wil2001@columbia.edu.
#
Contributed equally

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.

KEYWORDS:

VirCapSeq-VERT; acute flaccid myelitis; antibodies; enterovirus; enterovirus D-68; peptide array; serology

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