Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON, M5T 0S8, Canada.
Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Arthritis Res Ther. 2023 Feb 10;25(1):21. doi: 10.1186/s13075-023-02997-w.
Elevated levels of interferons (IFNs) are a characteristic feature of systemic autoimmune rheumatic diseases (SARDs) and may be useful in predicting impending symptomatic progression in anti-nuclear antibody-positive (ANA) individuals lacking a SARD diagnosis. Typically, these are measured by their effect on gene expression in the blood, which has limited their utility in clinical settings. Here, we assessed whether the measurement of serum IFN-α or selected IFN-induced cytokines accurately mirrors IFN-induced gene expression in ANA individuals and investigated their utility as biomarkers of clinical progression.
A total of 280 subjects were studied, including 50 ANA healthy controls, 160 ANA individuals without a SARD diagnosis (96 asymptomatic, 64 with undifferentiated connective tissue disease), and 70 SARD patients. IFN-induced gene expression was measured by nanoString and cytokine levels by ELISA or Simoa. ANA individuals lacking a SARD diagnosis who had the new onset of SARD criteria over the subsequent 2 years were defined as progressors.
Measurement of IFN-α levels by high-sensitivity ELISA or Simoa correlated much better with IFN-induced gene expression than measurement of CXCL-10 or Galectin-9 levels. Despite this, high CXCL-10 and Galectin-9 levels were better predictors of subsequent progression in ANA individuals than measures of IFN-α or IFN-induced gene expression with the optimal combination of predictive cytokines (CXCL-10 and IFN-α as measured by ELISA), resulting in a specificity and positive predictive value of 100%.
Easily performed ELISA assays for CXCL-10 and IFN-α can be used to predict ANA individuals at high risk of imminent symptomatic progression.
干扰素（IFNs）水平升高是系统性自身免疫性风湿病（SARD）的一个特征，可用于预测抗核抗体（ANA）阳性但尚未确诊为 SARD 的个体即将出现症状性进展。通常，通过它们对血液中基因表达的影响来测量 IFN，这限制了它们在临床环境中的应用。在这里，我们评估了血清 IFN-α或选定的 IFN 诱导细胞因子是否能准确反映 ANA 个体中的 IFN 诱导基因表达，并研究了它们作为临床进展生物标志物的效用。
共研究了 280 名受试者，包括 50 名 ANA 健康对照者、160 名无 SARD 诊断的 ANA 个体（96 名无症状，64 名未分化结缔组织病）和 70 名 SARD 患者。通过 nanoString 测量 IFN 诱导基因表达，通过 ELISA 或 Simoa 测量细胞因子水平。在随后的 2 年内新出现 SARD 标准的无 SARD 诊断的 ANA 个体被定义为进展者。
通过高灵敏度 ELISA 或 Simoa 测量 IFN-α水平与 IFN 诱导基因表达的相关性远优于测量 CXCL-10 或半乳糖凝集素-9 水平。尽管如此，高 CXCL-10 和半乳糖凝集素-9 水平在 ANA 个体中比 IFN-α或 IFN 诱导基因表达的测量更能预测随后的进展，最佳预测细胞因子的组合（ELISA 测量的 CXCL-10 和 IFN-α）具有 100%的特异性和阳性预测值。
CXCL-10 和 IFN-α 的易于进行的 ELISA 检测可用于预测即将出现症状性进展的 ANA 个体的高风险。
