Centre for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, 246 Clayton Road, Clayton, VIC 3168, Australia.
Department of Medicine and Rheumatology, The University of Melbourne at St. Vincent's Hospital, Melbourne, Australia.
Sci Rep. 2018 Feb 19;8(1):3268. doi: 10.1038/s41598-018-20203-9.
Type I interferon (IFN) pathways are significant in SLE pathogenesis. Less is known about the utility of measuring markers of IFN activity in patients, or whether patient subsets with different profiles exist. We explored the longitudinal associations of IFN-induced chemokines with disease activity in a cohort of SLE patients. We calculated a validated composite score (IFN-CK) of three type I IFN-inducible chemokines (CCL2/CXCL10/CCL19) measured in 109 SLE patients (median 7 occasions over 3.2 years). Longitudinal associations of IFN-CK score with disease activity (SLEDAI-2K) and other variables were assessed using general estimating equation (GEE) methods. IFN-CK was detectable in all patients. SLEDAI-2K was significantly associated with IFN-CK, damage score and prednisolone dose. SLEDAI-2K remained significantly associated with IFN-CK over time after adjustment of covariates. Patients with high time-adjusted mean IFN-CK had lower complement and higher time-adjusted disease activity. Concordance between IFN-CK and SLEDAI-2K varied widely among patients, with some individuals having none, others weak, and a subset very high concordance. In summary in our cohort of SLE patients, serum IFN-CK varied over time with disease activity, but with wide variation in concordance. Differing relationships between IFN pathway activation and disease activity may be valuable in assigning patients to emerging IFN-pathway targeting treatments.
I 型干扰素(IFN)途径在系统性红斑狼疮(SLE)发病机制中具有重要作用。对于测量 IFN 活性标志物在患者中的应用价值,或者是否存在具有不同特征的患者亚组,人们了解较少。我们在一组 SLE 患者中探索了 IFN 诱导的趋化因子与疾病活动的纵向关联。我们计算了三种 I 型 IFN 诱导的趋化因子(CCL2/CXCL10/CCL19)的验证综合评分(IFN-CK),这些趋化因子在 109 例 SLE 患者中进行了测量(中位数为 3.2 年内 7 次)。使用广义估计方程(GEE)方法评估 IFN-CK 评分与疾病活动(SLEDAI-2K)和其他变量的纵向关联。所有患者均可检测到 IFN-CK。SLEDAI-2K 与 IFN-CK、损伤评分和泼尼松剂量显著相关。在调整协变量后,IFN-CK 仍与 SLEDAI-2K 随时间显著相关。时间调整平均 IFN-CK 高的患者补体水平较低,时间调整疾病活动度较高。IFN-CK 与 SLEDAI-2K 之间的一致性在患者之间差异很大,一些患者无相关性,一些患者相关性较弱,而一部分患者的相关性非常高。总之,在我们的 SLE 患者队列中,血清 IFN-CK 随疾病活动而随时间变化,但一致性差异很大。IFN 途径激活与疾病活动之间的不同关系可能有助于将患者分配到新兴的 IFN 途径靶向治疗中。