Expresión de SIGLEC-1 en monocitos como biomarcador diagnóstico en enfermedades pediátricas mediadas por interferón...

Type I interferon (IFN)-mediated diseases present diagnostic challenges due to heterogeneous clinical manifestations and limitations of current molecular diagnostics, such as the Type I IFN Score (IS).

To evaluate SIGLEC-1 expression on monocytes as a practical biomarker for Type I IFN activation.

We conducted a combined retrospective (n=47) and prospective (n=62) study of patients with suspected IFN-mediated diseases. SIGLEC-1 expression was quantified by flow cytometry as mean fluorescence intensity (MFI) and percentage of SIGLEC-1⁺ monocytes. Analytical robustness was assessed in 52 paired samples comparing whole blood vs PBMCs and two cytometers (BD Fortessa vs BD Lyric). Fold-change (FC) normalization was evaluated to reduce inter-instrument variability.

In the retrospective cohort, SIGLEC-1 MFI and % SIGLEC-1⁺ monocytes strongly correlated with the Type I IS (R²=0.76; p<0.0001), with excellent diagnostic accuracy (AUC 0.99 and 0.98). In 11 patients with paired samples (high and low IS), SIGLEC-1 decreased in parallel with the IS. In the prospective cohort, optimized MFI and percentage cut-offs (2307 and 40.65) perfectly discriminated patients with interferonopathies from those with alternative diagnoses (AUC = 1.0). Analytical validation showed that although absolute values differed between PBMCs and whole blood, correlations were strong (R² > 0.97) and diagnostic classification was maintained. Similarly, Lyric values were lower than Fortessa but remained highly correlated (R²>0.93) with stable classification. FC normalization (cut-offs: 4.7 for MFI; 12 for %) minimized platform variability while preserving 100% sensitivity and specificity.

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.