Gerges Elias, Cauvet Anne, Schwarz Maximilian, Avouac Jérôme, Allanore Yannick
Institut Cochin, INSERM U1016 CNRS UMR8104, Université Paris Cité, Paris, France.
Rheumatology Department, Université Paris Cité, Cochin Hospital, APHP, Paris, France.
Rheumatology (Oxford). 2025 May 1;64(5):2792-2801. doi: 10.1093/rheumatology/keae546.
To determine serum type I IFN (IFN-α2a) concentrations in SSc patients, explore its association with cytokine/chemokine expressions and evaluate correlation with the phenotype including the predictive value for interstitial lung disease (ILD) progression.
Serum samples were obtained from 200 SSc patients and 29 healthy controls. IFN-α2a levels were measured by ultrasensitive electrochemiluminescence assay. Pro-inflammatory and chemokine panels were determined by Luminex® Discovery Assay multiplex kit. Baseline SSc disease characteristics were recorded together with longitudinal data for determining ILD progression after 2 years.
IFN-α2a concentrations were higher in SSc patients compared with controls, although not reaching significance [means ± SD of 49.20 ± 156.8 fg/ml vs 9.606 ± 4.399 fg/ml, respectively (P = 0.158)]. Using the cut-off of 15.9 fg/ml, we identified 62 patients as having a type 1 (T1) IFN signature in their circulation. Patients with an IFN signature had significantly higher levels of chemokines (CCL8, CCL19, CXCL10, CXCL11) and the cytokine IL-1α compared with those without an IFN signature. IFN-α2a concentrations strongly correlated with a T1 IFN-related chemokine score supporting activation of this pathway. Phenotyping association queries revealed association between IFN values and both skin and ILD involvements at baseline. Longitudinal data did not identify IFN as a predictive marker for ILD progression.
Using serum determinations, the activation of the T1 IFN pathway showed strong correlations with inflammatory mediators and associations with clinical manifestations, especially skin fibrosis and ILD in SSc patients. However, activated IFN pathway was not predictive of ILD progression.
测定系统性硬化症（SSc）患者血清I型干扰素（IFN-α2a）浓度，探讨其与细胞因子/趋化因子表达的关联，并评估其与包括间质性肺病（ILD）进展预测价值在内的表型的相关性。
采集200例SSc患者和29例健康对照者的血清样本。采用超灵敏电化学发光法测定IFN-α2a水平。通过Luminex® Discovery Assay多重试剂盒测定促炎因子和趋化因子组。记录SSc疾病的基线特征以及纵向数据，以确定2年后ILD的进展情况。
与对照组相比，SSc患者的IFN-α2a浓度更高，但未达到显著水平[分别为49.20±156.8 fg/ml和9.606±4.399 fg/ml，平均值±标准差（P = 0.158）]。以15.9 fg/ml为临界值，我们确定62例患者循环中有1型（T1）干扰素特征。有干扰素特征的患者与无干扰素特征的患者相比，趋化因子（CCL8、CCL19、CXCL10、CXCL11）和细胞因子IL-1α水平显著更高。IFN-α2a浓度与支持该途径激活的T1干扰素相关趋化因子评分密切相关。表型关联查询显示，IFN值与基线时的皮肤和ILD受累情况均有关联。纵向数据未将IFN确定为ILD进展的预测标志物。
通过血清检测，T1干扰素途径的激活与炎症介质密切相关，并与临床表现有关联，特别是在SSc患者中的皮肤纤维化和ILD。然而，激活的干扰素途径并不能预测ILD的进展。
