The interferon gene signature as a clinically relevant biomarker in autoimmune rheumatic disease
The interferon gene signature as a clinically relevant biomarker in autoimmune rheumatic disease
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DOI：
10.1016/s2665-9913(21)00254-x
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发表时间：
2021-12-23
影响因子：
25.4
通讯作者：
Isaacs, John D.
中科院分区：
文献类型：
--
作者：
Cooles, Faye A. H.;Isaacs, John D.
干扰素基因特征 (IGS) 源自干扰素调节基因的表达，并且通常会随着 I 型干扰素暴露而增加。随着测序技术的进步，风湿性疾病中全血 IGS 升高的报道越来越多。尽管其作用尚不清楚，但我们探讨了升高的 IGS 如何作为临床相关生物标志物发挥作用，而不管它是旁观者效应还是关键病理过程。例如，在预测患有关节痛和抗瓜氨酸蛋白抗体的患者中的类风湿性关节炎，或预测具有抗核抗体的患者中的系统性红斑狼疮 (SLE) 时，升高的 IGS 可以作为诊断生物标志物；预测接受疾病修饰治疗（例如治疗类风湿性关节炎的利妥昔单抗）患者的反应时的治疗诊断生物标志物；疾病活动的生物标志物（早期类风湿性关节炎、皮肌炎、系统性硬化症、SLE）；或者最终是临床特征的预测因子，例如系统性红斑狼疮中的狼疮性肾炎或原发性干燥综合征中的疾病负担。高IGS并不能统一预测所有疾病的较差临床表型（如原发性干燥综合征疾病负担减轻所证明的那样），也不能预测对所有治疗的普遍较差的反应（如类风湿性关节炎）。这种二分法凸显了体内 I 型干扰素信号传导的复杂性以及当前计算 IGS 时缺乏标准化的情况。 IGS 作为生物标志物值得进一步探索，预计在多种风湿性疾病中具有有益的临床应用。
The interferon gene signature (IGS) is derived from the expression of interferon-regulated genes and is classically increased in response to type I interferon exposure. A raised whole blood IGS has increasingly been reported in rheumatic diseases as sequencing technology has advanced. Although its role remains unclear, we explore how a raised IGS can function as a clinically relevant biomarker, independent of whether it is a bystander effect or a key pathological process. For example, a raised IGS can act as a diagnostic biomarker when predicting rheumatoid arthritis in patients with arthralgia and anti-citrullinated protein antibodies, or predicting systemic lupus erythematous (SLE) in those with antinuclear antibodies; a theragnostic biomarker when predicting response for patients receiving disease modifying therapy, such as rituximab in rheumatoid arthritis; a biomarker of disease activity (early rheumatoid arthritis, dermatomyositis, systemic sclerosis, SLE); or finally a predictor of clinical characteristics, such as lupus nephritis in SLE or disease burden in primary Sjogren's syndrome. A high IGS does not uniformly predict worse clinical phenotypes across all diseases, as demonstrated by a reduced disease burden in primary Sjogren's syndrome, nor does it predict a universally poorer response to all therapies, as shown in rheumatoid arthritis. This dichotomy highlights both the complexity of type I interferon signalling in vivo and the current lack of standardisation when calculating the IGS. The IGS as a biomarker warrants further exploration, with beneficial clinical applications anticipated in multiple rheumatic diseases.