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. 2025 Jun 1;64(6):3938-3946.
doi: 10.1093/rheumatology/keae643.

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

Valentina Natoli  1   2   3 , Yanick J Crow  4   5 , David P J Hunt  6   7 , Kukatharmini Tharmaratnam  8 , Andrea L Jorgensen  8 , Michael W Beresford  1   9 , Christian M Hedrich  1   9 , Eve M D Smith  1   9
Affiliations

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

Valentina Natoli et al. Rheumatology (Oxford). .

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.

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Figures

Figure 1.
Figure 1.
Cross-sectional analysis of serum IFN-α2 in jSLE (according to disease activity), JIA patients and HCs . (A) Comparison of serum IFN-α2 levels in jSLE (n = 88), JIA (n = 35) and HCs (n = 28). (B) Comparison of serum IFN-α2 levels in jSLE patients (n = 88) stratified for disease activity state. Statistically significant post-hoc adjusted P-values are displayed. *P ≤0.05; **P ≤0.01; ***P ≤0.001. HCs: healthy controls; IFN-α2: interferon-alpha2; JIA: juvenile idiopathic arthritis; jSLE: juvenile systemic lupus erythematosus; LDAS: low disease activity state
See this image and copyright information in PMC

References

    1. Ambrose N, Morgan TA, Galloway J et al.; UK JSLE Study Group. Differences in disease phenotype and severity in SLE across age groups. Lupus 2016;25:1542–50. - PMC - PubMed
    1. Smith EMD, Lythgoe H, Midgley A, Beresford MW, Hedrich CM. Juvenile-onset systemic lupus erythematosus: update on clinical presentation, pathophysiology and treatment options. Clin Immunol 2019;209:108274. - PubMed
    1. Chen Y-M, Lin C-H, Chen H-H et al. Onset age affects mortality and renal outcome of female systemic lupus erythematosus patients: a nationwide population-based study in Taiwan. Rheumatology 2014;53:180–5. - PubMed
    1. Floris A, Piga M, Cauli A, Mathieu A. Predictors of flares in Systemic Lupus Erythematosus: preventive therapeutic intervention based on serial anti-dsDNA antibodies assessment. Analysis of a monocentric cohort and literature review. Autoimmun Rev 2016;15:656–63. - PubMed
    1. Hedrich CM, Smith EMD, Beresford MW. Juvenile-onset systemic lupus erythematosus (jSLE) – pathophysiological concepts and treatment options. Best Practice & Research Clinical Rheumatology 2017;31:488–504. - PubMed