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Author Spotlight: Advancing Immune Monitoring in Critical Care Patients Using Whole Blood Assays
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A Broad-Spectrum Infection Diagnostic that Detects Pathogen-Associated Molecular Patterns (PAMPs) in Whole Blood

Mark Cartwright1, Martin Rottman2, Nathan I Shapiro3

  • 1Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.

Ebiomedicine
|June 23, 2016
PubMed
Abstract

Insights

A new Enzyme-Linked Lectin-Sorbent Assay (ELLecSA) rapidly detects pathogen-associated molecular patterns (PAMPs) in blood. This assay shows promise for diagnosing bloodstream infections, even when blood cultures are negative.

Area of Science:

  • Infectious Disease Diagnostics
  • Biomarker Discovery
  • Immunology

Background:

  • Current blood culture and molecular tests often fail to detect bloodstream infections.
  • A rapid diagnostic test is needed to improve sepsis patient triage and therapy.
  • Existing methods lack sensitivity and speed for timely infection diagnosis.

Purpose of the Study:

  • To develop and evaluate a novel assay for rapid detection of pathogen-associated molecular patterns (PAMPs) in whole blood.
  • To assess the diagnostic performance of the FcMBL ELLecSA in animal models and human patients with suspected sepsis.
  • To compare the assay's specificity against trauma-related inflammation and C-reactive Protein.

Main Methods:

  • Development of an Enzyme-Linked Lectin-Sorbent Assay (ELLecSA) using engineered Mannose Binding Lectin (FcMBL) on magnetic microbeads.
  • Quantification of PAMPs in whole blood from infected rats and pigs, and prospectively enrolled emergency room patients.
  • Comparison of FcMBL ELLecSA results with blood cultures, C-reactive Protein levels, and data from non-infected patients.

Main Results:

  • The FcMBL ELLecSA detected PAMPs from 85% of clinical isolates across 47 species, including common sepsis pathogens.
  • The assay provided rapid (<1h) detection of active infection in animals, outperforming blood cultures and antibiotic treatment.
  • In patients, the FcMBL ELLecSA achieved >81% sensitivity, >89% specificity, and 0.87 accuracy for sepsis detection, distinguishing infection from trauma.

Conclusions:

  • The FcMBL ELLecSA offers a rapid, sensitive, and specific method for diagnosing infections, even with negative blood cultures or ongoing antibiotic therapy.
  • This PAMP assay can aid in triaging suspected systemic infections and guiding sepsis therapies.
  • The assay demonstrates potential as a companion diagnostic for novel sepsis treatments.
Keywords:
BiomarkerBlood cultureC-reactive proteinInfection diagnosticMannose binding lectinSepsis

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