Natoli Valentina, Crow Yanick J, Hunt David P J, Tharmaratnam Kukatharmini, Jorgensen Andrea L, Beresford Michael W, Hedrich Christian M, Md Smith Eve
Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, UK.
Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università degli Studi di Genova, Genoa, Italy.
Rheumatology (Oxford). 2024 Nov 26. doi: 10.1093/rheumatology/keae643.
This study investigated serum IFN-α2 as a putative marker of disease activity and predictor of disease flares in juvenile systemic lupus erythematosus (jSLE).
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.
Cross-sectional analysis showed higher median IFN-α2 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-α2 levels had a shorter time to flare over the subsequent six months compared to 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).
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.
本研究调查了血清干扰素-α2（IFN-α2）作为青少年系统性红斑狼疮（jSLE）疾病活动的假定标志物和疾病复发预测指标的情况。
分析了222份血清样本，包括28名健康对照者（HCs）、88例jSLE患者（159份样本）和35例青少年特发性关节炎（JIA）患者。使用单分子阵列（Simoa）测定IFN-α2水平。横断面分析比较了患者组和疾病活动状态亚组之间的IFN-α2中位数水平。通过线性回归分析疾病复发时间。纵向分析中，通过广义线性混合模型评估IFN-α2和其他传统生物标志物（红细胞沉降率/ESR、低C3和抗双链DNA抗体）检测和预测疾病复发的能力。
横断面分析显示，与低疾病活动状态（LDAS）组（中位数571 fg/mL，四分位间距IQR 57 - 1310 fg/mL，p = 0.04）和缓解亚组（271 fg/mL，IQR 3 - 56，p < 0.001）相比，活动/中间组的IFN-α2中位数水平更高（中位数3185 fg/mL，IQR 48 - 13703）。与JIA患者（中位数7 fg/mL，IQR 3 - 236，p = 0.0017）和HCs（p = 0.017）相比，所有jSLE患者的IFN-α2水平更高（中位数587 fg/mL，IQR 11 - 2774）。与IFN-α2水平正常的jSLE缓解期或LDAS患者相比，IFN-α2水平异常的患者在随后六个月内疾病复发时间更短（p = 0.022）。纵向分析中，多变量分析表明高IFN-α2是疾病持续复发的唯一预测指标（p = 0.028）。
血清IFN-α2水平与疾病活动相关，可预测jSLE患者当前及未来的疾病复发。这些发现表明，IFN-α2的定量检测可能有助于这些患者的风险分层和疾病监测。
