The Journal of allergy and clinical immunology · 2026
SIGLEC-1 expression on monocytes as a diagnostic biomarker in pediatric type I interferon-mediated diseases.
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Matteo Valentina, Zeric Hana, Loricchio Elena, Caiello Ivan, Martella Aurora, Ferri Giulia, Guarracino Federica, Agrati Chiara, Federici Silvia, Nicita Francesco, Bracaglia Claudia, Nicolai Rebecca, Messia Virginia, Palumbo Giuseppe, Insalaco Antonella, De Benedetti Fabrizio, Prencipe Giusi
Аннотация
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: We conducted a combined retrospective (n = 47) and prospective (n = 62) study of patients with suspected interferon-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 versus PBMCs and 2 cytometers (BD Fortessa vs BD Lyric). Fold-change normalization was evaluated to reduce interinstrument variability.
RESULTS: In the retrospective cohort, SIGLEC-1 MFI and percentage of SIGLEC-1+ monocytes strongly correlated with the type I IS (R2 = 0.76; P < .0001), with excellent diagnostic accuracy (area under the curve [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 cutoffs (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. 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.
OBJECTIVES: We sought to evaluate SIGLEC-1 expression on monocytes as a practical biomarker for type I interferon activation.
METHODS: We conducted a combined retrospective (n = 47) and prospective (n = 62) study of patients with suspected interferon-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 versus PBMCs and 2 cytometers (BD Fortessa vs BD Lyric). Fold-change normalization was evaluated to reduce interinstrument variability.
RESULTS: In the retrospective cohort, SIGLEC-1 MFI and percentage of SIGLEC-1+ monocytes strongly correlated with the type I IS (R2 = 0.76; P < .0001), with excellent diagnostic accuracy (area under the curve [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 cutoffs (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. 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.