Weiden Christina, Saers Melanie, Schwarz Tobias, Hinze Tanja, Wittkowski Helmut, Kessel Christoph, Masjosthusmann Katja, Mohr Michael, Evers Georg, Oesingmann-Weirich Sandra, Foell Dirk, Hinze Claas H
University Hospital Muenster, Muenster, Germany.
St. Josef-Stift, Sendenhorst, Germany.
ACR Open Rheumatol. 2023 Dec;5(12):652-662. doi: 10.1002/acr2.11618. Epub 2023 Oct 2.
Rheumatic diseases are characterized by different patterns of immune overactivation. This study investigated the correlation of whole blood type 1 interferon (IFN) stimulated gene (ISG), IL18, and CXCL9 expression with clinical disease activity in pediatric rheumatic diseases and assessed the required number of ISGs to be included in a composite type 1 IFN score.
Whole blood-derived RNA and clinical data were collected from 171 mostly pediatric patients with connective tissue diseases (CTDs), systemic autoinflammatory diseases (SAIDs), monogenic interferonopathies (IFNPs) and other inflammatory diseases, and from 38 controls. The expression of six previously established ISGs, IL18, and CXCL9 was assessed by real-time polymerase chain reaction (471 samples). Individual and composite gene expression was assessed, and correlation and threshold analyses were performed.
Correlation between ISG expression and clinical disease activity was strongest in CTD, especially in juvenile dermatomyositis (JDM) and IFNP, and modest in patients with SAID. Threshold ISG expression levels for the detection of at least mild clinical disease activity were substantially higher in patients with systemic lupus erythematosus compared with JDM. The correlation of expression levels of limited sets of ISGs and even individual ISGs with clinical disease activity were not inferior to a composite score of six ISGs.
In a real-world cohort, individual ISG expression levels robustly reflected clinical disease activity in CTD and IFNP, especially in JDM, which would simplify such analyses in clinical routine and be more cost-effective. Threshold levels varied across diseases, potentially reflecting different mechanisms of type 1 IFN overactivation.
风湿性疾病的特征是免疫过度激活模式各异。本研究调查了全血1型干扰素（IFN）刺激基因（ISG）、IL18和CXCL9表达与儿童风湿性疾病临床疾病活动度的相关性，并评估了纳入1型干扰素综合评分所需的ISG数量。
收集了171例主要为患有结缔组织病（CTD）、系统性自身炎症性疾病（SAID）、单基因干扰素病（IFNP）和其他炎症性疾病的儿科患者以及38例对照的全血来源RNA和临床数据。通过实时聚合酶链反应评估6个先前确定的ISG、IL18和CXCL9的表达（471个样本）。评估了个体和复合基因表达，并进行了相关性和阈值分析。
ISG表达与临床疾病活动度之间的相关性在CTD中最强，尤其是在幼年皮肌炎（JDM）和IFNP中，在SAID患者中则较弱。与JDM相比，系统性红斑狼疮患者检测至少轻度临床疾病活动度的ISG阈值表达水平要高得多。有限组ISG甚至单个ISG的表达水平与临床疾病活动度的相关性并不亚于6个ISG的综合评分。
在一个真实世界队列中，个体ISG表达水平有力地反映了CTD和IFNP中的临床疾病活动度，尤其是在JDM中，这将简化临床常规中的此类分析并更具成本效益。阈值水平因疾病而异，可能反映了1型干扰素过度激活的不同机制。
