Department of Immunology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Rheumatology (Oxford). 2018 May 1;57(5):921-930. doi: 10.1093/rheumatology/kex490.
To assess the relationships between systemic IFN type I (IFN-I) and II (IFN-II) activity and disease manifestations in primary SS (pSS).
RT-PCR of multiple IFN-induced genes followed by principal component analysis of whole blood RNA of 50 pSS patients was used to identify indicator genes of systemic IFN-I and IFN-II activities. Systemic IFN activation levels were analysed in two independent European cohorts (n = 86 and 55, respectively) and their relationships with clinical features were analysed.
Three groups could be stratified according to systemic IFN activity: IFN inactive (19-47%), IFN-I (53-81%) and IFN-I + II (35-55%). No patient had isolated IFN-II activation. IgG levels were highest in patients with IFN-I + II, followed by IFN-I and IFN inactive patients. The prevalence of anti-SSA and anti-SSB was higher among those with IFN activation. There was no difference in total-EULAR SS Disease Activity Index (ESSDAI) or ClinESSDAI between the three subject groups. For individual ESSDAI domains, only the biological domain scores differed between the three groups (higher among the IFN active groups). For patient reported outcomes, there were no differences in EULAR Sjögren's syndrome patient reported index (ESSPRI), fatigue or dryness between groups, but pain scores were lower in the IFN active groups. Systemic IFN-I but not IFN-I + II activity appeared to be relatively stable over time.
Systemic IFN activation is associated with higher activity only in the ESSDAI biological domain but not in other domains or the total score. Our data raise the possibility that the ESSDAI biological domain score may be a more sensitive endpoint for trials targeting either IFN pathway.
评估原发性干燥综合征（pSS）患者全身Ⅰ型干扰素（IFN-I）和Ⅱ型干扰素（IFN-II）活性与疾病表现之间的关系。
采用多重 IFN 诱导基因 RT-PCR 联合全血 RNA 主成分分析，对 50 例 pSS 患者进行分析，以鉴定全身 IFN-I 和 IFN-II 活性的指标基因。在两个独立的欧洲队列（分别为 86 例和 55 例）中分析了全身 IFN 激活水平，并分析了其与临床特征的关系。
根据全身 IFN 活性可将患者分为三组：IFN 无活性（19%-47%）、IFN-I（53%-81%）和 IFN-I+II（35%-55%）。没有患者单独出现 IFN-II 激活。IFN-I+II 组患者 IgG 水平最高，其次是 IFN-I 组和 IFN 无活性组。具有 IFN 激活的患者抗 SSA 和抗 SSB 的发生率更高。三组患者的总-EULAR 干燥综合征疾病活动指数（ESSDAI）或临床 ESSDAI 无差异。对于各个 ESSDAI 域，只有三个组之间的生物学域评分不同（IFN 活性组较高）。对于患者报告的结局，三组之间在 EULAR 干燥综合征患者报告指数（ESSPRI）、疲劳或干燥方面无差异，但 IFN 活性组的疼痛评分较低。全身 IFN-I 而不是 IFN-I+II 活性似乎随时间相对稳定。
全身 IFN 激活与 ESSDAI 生物学域的更高活动相关，但与其他域或总分无关。我们的数据提出了一种可能性，即 ESSDAI 生物学域评分可能是针对 IFN 通路的试验更敏感的终点。
