Phage Immunoprecipitation Sequencing Links Enterovirus D68 to Guillain-Barré Syndrome

Overview

Phage immunoprecipitation sequencing (PhIP-Seq) was utilized to detect cerebrospinal fluid antibodies against enterovirus D68 (EV-D68) in a pediatric Guillain-Barré syndrome (GBS) case, supporting EV-D68 as an antecedent infectious trigger. This approach enabled etiological diagnosis where conventional molecular testing was inconclusive.

Background

Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy characterized by ascending flaccid paralysis, often following respiratory or gastrointestinal infections. The pathogenesis involves immune-mediated nerve damage triggered by molecular mimicry after infection. Common infectious agents include Campylobacter jejuni and various viruses, with recent evidence implicating EV-D68. Diagnosing antecedent infections is challenging due to low pathogen detection in cerebrospinal fluid (CSF) during neurologic symptom onset.

Data Highlights

A 6-year-old female presented with progressive ascending weakness and cranial nerve involvement following EV-D68 respiratory infection confirmed by PCR. PhIP-Seq detected intrathecal antibodies against enterovirus D in CSF, correlating with clinical GBS diagnosis. Control specimens included CSF from neurologic patients with negative viral testing and sera from EV-D68 PCR-confirmed respiratory cases without neurologic symptoms.

Key Findings

• GBS is often preceded by infections, but direct pathogen detection in CSF is frequently negative due to timing and low pathogen load.
• PhIP-Seq enables detection of intrathecal antibody production against specific pathogens, providing evidence of antecedent infection.
• In the reported pediatric case, PhIP-Seq identified anti-enterovirus D antibodies in CSF, linking EV-D68 respiratory infection to GBS onset.
• Clinical presentation included progressive ascending weakness, cranial nerve palsy, and respiratory failure requiring intensive care.
• PhIP-Seq may improve etiological diagnosis of GBS and other acute flaccid paralysis cases where conventional testing is inconclusive.

Clinical Implications

PhIP-Seq offers a valuable diagnostic tool to detect intrathecal antibody responses in GBS patients, facilitating identification of antecedent infectious triggers such as EV-D68. This can guide clinical management and epidemiological understanding of GBS etiology, especially when standard CSF pathogen detection methods fail. Early recognition of EV-D68 involvement may influence monitoring and supportive care strategies in pediatric GBS cases.

Conclusion

Phage immunoprecipitation sequencing successfully identified EV-D68 antibodies in CSF, supporting its role as a contributing factor in GBS. This method enhances diagnostic accuracy for infection-associated neurologic syndromes where direct pathogen detection is limited.

References

1. Original Article -- Utilization of Phage Immunoprecipitation Sequencing for Diagnosing Enterovirus D68 as a Contributing Factor in Guillain-Barré Syndrome Cases