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Particle Agglutination Method for Poliovirus Identification
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Pan-viral serology implicates enteroviruses in acute flaccid myelitis

Ryan D Schubert1,2, Isobel A Hawes1,2, Prashanth S Ramachandran1,2

  • 1Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

Nature Medicine
|October 23, 2019
PubMed

Insights

Pediatric acute flaccid myelitis (AFM) spikes are linked to non-polio enteroviruses (EVs). Intrathecal antibodies in cerebrospinal fluid (CSF) suggest EVs cause AFM, even when viral RNA is undetectable.

Area of Science:

  • Virology
  • Neuroimmunology
  • Epidemiology

Background:

  • Pediatric acute flaccid myelitis (AFM) exhibits biennial spikes in the US since 2012.
  • Non-polio enteroviruses (EVs) are suspected causes, but EV RNA is seldom found in cerebrospinal fluid (CSF).

Purpose of the Study:

  • To investigate the role of intrathecal antibodies in AFM etiology.
  • To identify potential viral triggers for AFM using advanced serological and sequencing techniques.

Main Methods:

  • Phage display (VirScan) was used to detect intrathecal antibodies against a broad range of viruses in AFM patient CSF.
  • Metagenomic next-generation sequencing (mNGS) was performed on CSF RNA.
  • Enzyme-linked immunosorbent assay (ELISA) targeting EV VP1 was used for confirmation.

Main Results:

  • VirScan identified significantly enriched antibodies against Picornaviridae, specifically Enterovirus (EV), in AFM cases compared to controls.
  • EV VP1 ELISA confirmed a higher prevalence of EV-specific antibodies in AFM patients.
  • mNGS did not detect additional EV RNA, but pan-viral serology revealed high CSF EV-specific antibody levels in AFM cases.

Conclusions:

  • Despite low viral RNA detection, frequent identification of EV-specific antibodies in CSF strongly supports a causal role for non-polio EVs in AFM.
  • This study highlights the utility of pan-viral serology in diagnosing viral-associated neurological diseases.

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