Cooles Faye A H, Isaacs John D
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Lancet Rheumatol. 2022 Jan;4(1):e61-e72. doi: 10.1016/S2665-9913(21)00254-X. Epub 2021 Nov 17.
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 Sjögren's syndrome. A high IGS does not uniformly predict worse clinical phenotypes across all diseases, as demonstrated by a reduced disease burden in primary Sjögren'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.
干扰素基因特征（IGS）源自干扰素调节基因的表达，经典情况下，其在暴露于I型干扰素时会升高。随着测序技术的进步，越来越多的研究报道了在风湿性疾病中全血IGS升高的情况。尽管其作用仍不明确，但我们探讨了升高的IGS如何作为一种临床相关的生物标志物发挥作用，而不考虑它是旁观者效应还是关键的病理过程。例如，升高的IGS在预测关节痛和抗瓜氨酸化蛋白抗体患者的类风湿关节炎，或抗核抗体患者的系统性红斑狼疮（SLE）时可作为诊断生物标志物；在预测接受疾病改善治疗（如类风湿关节炎中的利妥昔单抗）的患者的反应时可作为治疗诊断生物标志物；作为疾病活动的生物标志物（早期类风湿关节炎、皮肌炎、系统性硬化症、SLE）；或者最终作为临床特征的预测指标，如SLE中的狼疮性肾炎或原发性干燥综合征中的疾病负担。如原发性干燥综合征中疾病负担降低所示，高IGS并非在所有疾病中都一致地预测更差的临床表型，类风湿关节炎的情况也表明，它也不能预测对所有治疗普遍更差的反应。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目前计算IGS时缺乏标准化的情况。IGS作为一种生物标志物值得进一步探索，预计在多种风湿性疾病中会有有益的临床应用。
