Monocyte Single-Cell-Type Gene Expression Analysis Differentiates Kawasaki Disease From Viral Infection With High Specificity.

Kawasaki disease (KD) and viral infection (VD) share similar clinical features but require distinct treatments. A practical biomarker to distinguish them is therefore clinically important. Previous blood transcriptome studies identified many differentially expressed genes, but large gene panels are impractical for routine laboratories. A ratio-based Direct Leukocyte Single-cell-type Transcript Abundance (DIRECT LS-TA) assay was recently developed to quantify monocyte gene expression directly in whole blood using a monocyte-specific target gene relative to monocyte reference genes (PSAP or CTSS). Interferon-stimulated genes IFI27, IFI44L, and SIGLEC1 can be measured by this approach. In this study, three ratio biomarkers (IFI27/PSAP, IFI44L/PSAP, SIGLEC1/PSAP) and a conventional interferon (IFN) score derived from eight genes were calculated from public blood transcriptome datasets (GSE73461 and GSE68004) and compared between KD and VD. VD patients showed markedly elevated IFN-related biomarkers, with all three ratios significantly higher in VD and IFI27/PSAP giving the largest increase. IFI27/PSAP achieved the highest diagnostic performance (AUC 0.90), slightly exceeding the conventional IFN score (AUC 0.89). These findings suggest that absent or minimal IFN activation argues against VD and supports KD, and that this simple ratio assay could serve as a clinically useful exclusion test.