SIGLEC-1 expression on monocytes as a diagnostic biomarker in pediatric type I interferon-mediated diseases

BACKGROUND: Type I interferon-mediated diseases present diagnostic challenges due to heterogeneous clinical manifestations and limitations of current molecular diagnostics, such as the type I interferon score (IS). OBJECTIVES: We sought to evaluate SIGLEC-1 expression on monocytes as a practical biomarker for type I interferon activation. METHODS: monocytes. Analytical robustness was assessed in 52 paired samples comparing whole blood versus PBMCs and 2 cytometers (BD Fortessa vs BD Lyric). Fold-change normalization was evaluated to reduce interinstrument variability. RESULTS: > 0.93) with stable classification. Fold-change normalization (cutoffs: 4.7 for MFI; 12 for %) minimized platform variability while preserving 100% sensitivity and specificity. CONCLUSIONS: Flow-cytometric SIGLEC-1 is a robust, cost-effective, and reproducible surrogate of type I IS, supporting its implementation for diagnosis, patient stratification, and longitudinal monitoring.