Elevated serum interferon-α2 associates with activity and flare risk in Juvenile-onset Systemic Lupus Erythematosus

Objectives: This study investigated serum IFN-a2 as a putative marker of disease activity and predictor of disease flares in juvenile systemic lupus erythematosus (jSLE).

Methods: 222 serum samples were analysed, including 28 healthy controls (HCs), 88 JSLE (159 samples), and 35 juvenile idiopathic arthritis (JIA) patients. IFN-a2 levels were determined using Single-molecule array (Simoa). Cross-sectionally, median IFN-a2 levels were compared between patient groups and disease activity state sub-groups. Time to flare was analysed by linear regression. Longitudinally, the ability of the IFN-a2 and other traditional biomarkers (erythrocyte sedimentation rate/ESR, low C3 and anti-dsDNA antibodies) to detect and predict flares was assessed via a generalised linear mixed model.

Results: Cross-sectional analysis showed higher median IFN-a2 levels in the active/intermediate group (median 3,185 fg/mL, IQR 48-13,703) compared to the LDAS (571 fg/mL, IQR 57-1,310 fg/mL, p=0.04) and remission sub-groups (271 fg/mL, IQR 3-56, p <0.001). IFN-α2 was higher in all JSLE patients (median 587 fg/mL, IQR 11-2,774) as compared to JIA patients (median 7 fg/mL, IQR 3-236, p=0.0017) and HCs (p=0.017). JSLE patients in remission or LDAS with abnormal IFN-a2 levels had a shorter time to flare over the subsequent six months compared to those with normal IFN-a2 levels (p=0.022). Longitudinally, multivariable analysis demonstrated high IFN-a2 to be the only predictor of an ongoing flare (p=0.028).

Conclusion: Serum IFN-α2 levels associate with disease activity and can predict ongoing and future flares in jSLE. These findings suggest that quantification of IFN-α2 may support risk stratification and disease monitoring in these patients.