Novel Diagnostic for Acute Influenza Virus Infection Using Circulating Antibody Secreting Cells

Background:

Surges of serum antibodies after immunization and infection are highly specific for the offending antigen, and recent studies demonstrate that viral infections induce transient increases in circulating antibody secreting cells (ASCs). High specificity of circulating ASC that lack bystander responses during acute infection highlight the diagnostic value of measuring ASCs as an ideal one-time-point immune surrogate compared to serology during acute infection. We have developed a novel test to diagnose acute influenza infection using circulating ASCs. 

Methods:

Specificity of influenza-specific ASC during acute infections in patients with acute respiratory diseases (n = 134) was tested using influenza- or RSV-specific ASC ELISpot assays for IgM, IgG, IgA in the blood. Twenty-six healthy asymptomatic adults were also enrolled.

Results:

In the original pilot study of 23 influenza- and 37 RSV-confirmed adult respiratory infections, the test was positive with 80% sensitivity and 100% specificity. No influenza-specific ASCs were detected in the 26 healthy subjects. A second validation cohort of 74 adult subjects admitted with acute respiratory symptoms was tested by PCR analysis of nasal swabs and by ASC-based immunoassays for influenza and RSV. PCR was positive in 16/27 patients and the influenza-specific ASC assay was positive in 20/27 patients. Only 9 patients were positive by both the PCR and ASC assays. PCR-positive patients often presented earlier whereas ASC-positive assays occurred in those who presented later. Influenza types A and B, as well as subtypes H1 and H3, were discernible by the ASC assay. 

Conclusion:

Influenza-specific IgM, IgG, & IgA assays are effective in detecting acute influenza viral infections. PCR may have advantages earlier in diagnosis but ASC assays were advantageous in patients who presented later.