Beyond the surface: soluble SIGLEC-1 as a clinically applicable type I IFN biomarker

Area of Science:

• Immunology
• Biomarker Discovery
• Rheumatology

Background:

• Type I interferons (IFN-I) are crucial in systemic lupus erythematosus (SLE) pathogenesis and monitoring.
• Clinically accessible biomarkers for IFN-I activity in SLE are limited.
• Membrane-bound SIGLEC-1 (mbSIGLEC-1) has shown prior validation as a biomarker.

Purpose of the Study:

• To evaluate soluble SIGLEC-1 (sSIGLEC-1) as a potential biomarker for IFN-I activity in SLE.
• To assess the correlation of sSIGLEC-1 with disease activity indices and other IFN-I biomarkers.
• To determine the clinical utility and scalability of sSIGLEC-1 in SLE patients.

Main Methods:

• Prospective enrollment of 61 SLE patients and 100 blood donors.
• Longitudinal assessment of disease activity indices (DAI), IFN-I biomarkers (IFNα, IP-10, mbSIGLEC-1), and sSIGLEC-1.
• Measurement of sSIGLEC-1 using chemiluminescence immunoassay and ROC analysis for threshold determination.
• Cross-sectional and longitudinal correlation analyses, including flare-predictive evaluation.

Main Results:

• A threshold for sSIGLEC-1 was established at 4.55 ng/ml with 70.49% sensitivity and 90% specificity.
• sSIGLEC-1 demonstrated significant cross-sectional correlations with mbSIGLEC-1, BILAG, SLEDAI, IFN-α, and IP-10.
• Longitudinal analysis showed correlations between changes in BILAG and changes in sSIGLEC-1 and mbSIGLEC-1.
• Both sSIGLEC-1 and mbSIGLEC-1 exhibited high sensitivity in moderate to severe SLE disease activity.

Conclusions:

• sSIGLEC-1 is a reliable and scalable biomarker for IFN-I activity in SLE.
• Its performance and compatibility with routine assays suggest strong potential for clinical translation.
• sSIGLEC-1 may find broader applications in monitoring other IFN-I-driven diseases.