Elevated serum interferon-α2 associates with activity and flare risk in juvenile-onset systemic lupus erythematosus

Abstract

Objectives: This study investigated serum IFN-α2 as a putative marker of disease activity and predictor of disease flares in juvenile systemic lupus erythematosus (jSLE).

Methods: A total of 222 serum samples were analysed, including 28 healthy controls (HCs), 88 jSLE (159 samples) and 35 juvenile idiopathic arthritis (JIA) patients. IFN-α2 levels were determined using single-molecule array (Simoa). Cross-sectionally, median IFN-α2 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-α2 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-α2 levels in the active/intermediate group (median 3185 fg/ml, IQR 48-13 703) compared with the LDAS (571 fg/ml, IQR 57-1310 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 11-2774) as compared with 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-α2 levels had a shorter time to flare over the subsequent six months compared with those with normal IFN-α2 levels (P = 0.022). Longitudinally, multivariable analysis demonstrated high IFN-α2 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.

Keywords: Simoa; biomarker; disease activity; flare; jSLE; type I IFN.