Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic.
Department of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic.
Clin Exp Rheumatol. 2020 Mar-Apr;38(2):289-298. doi: 10.55563/clinexprheumatol/qb2ha3. Epub 2019 Aug 3.
A growing body of evidence highlights the persistent activation of the innate immune system and type I interferon (IFN) signature in the pathogenesis of rheumatoid arthritis (RA) and its association with disease activity. Since the recent study revealed heterogeneity in the IFN signature in RA, we investigated for the first time the heterogeneity in innate signature in RA.
The innate gene expression signature (10 TLRs, 7 IL1/IL1R family members, and CXCL8/IL8) was assessed in peripheral blood mononuclear cells from RA patients (n=67), both with active (DAS28≥3.2, n=32) and inactive disease (DAS28<3.2, n=35), and in healthy control subjects (n=55).
Of the 13 deregulated innate genes (TLR2, TLR3, TLR4, TLR5, TLR8, TLR10, IL1B, IL1RN, IL18, IL18R1, IL1RAP, and SIGIRR/IL1R8) associated with RA, TLR10 and IL1RAP are being reported for the first time. Multivariate analysis based on utilising patient similarity networks revealed the existence of four patient's subsets (clusters) based on different TLR8 and IL1RN expression profiles, two in active and two in inactive RA. Moreover, neural network analysis identified two main gene sets describing active RA within an activity-related innate signature (TLR1, TLR2, TLR3, TLR7, TLR8, CXCL8/IL8, IL1RN, IL18R1). When comparing active and inactive RA, upregulated TLR2, TLR4, TLR6, and TLR8 and downregulated TLR10 (P<0.04) expression was associated with the disease activity.
Our study on the comprehensive innate gene profiling together with multivariate analysis revealed a certain heterogeneity in innate signature within RA patients. Whether the heterogeneity of RA elucidated from diversity in innate signatures may impact the disease course and treatment response deserves future investigations.
越来越多的证据表明，固有免疫系统的持续激活和 I 型干扰素（IFN）特征在类风湿关节炎（RA）的发病机制及其与疾病活动度的相关性中起着重要作用。由于最近的研究揭示了 RA 中 IFN 特征的异质性，我们首次研究了 RA 中固有特征的异质性。
评估了来自 RA 患者（活跃疾病 DAS28≥3.2，n=32；不活跃疾病 DAS28<3.2，n=35）和健康对照者（n=55）外周血单个核细胞中的固有基因表达特征（10 个 TLRs、7 个 IL1/IL1R 家族成员和 CXCL8/IL8）。
与 RA 相关的 13 个失调固有基因（TLR2、TLR3、TLR4、TLR5、TLR8、TLR10、IL1B、IL1RN、IL18、IL18R1、IL1RAP 和 SIGIRR/IL1R8）中，TLR10 和 IL1RAP 是首次报道。基于利用患者相似性网络的多变量分析，根据不同的 TLR8 和 IL1RN 表达谱，发现了四个患者亚组（簇）的存在，两个在活跃 RA 中，两个在不活跃 RA 中。此外，神经网络分析确定了两个主要基因集，用于描述与活性相关的固有特征内的活跃 RA（TLR1、TLR2、TLR3、TLR7、TLR8、CXCL8/IL8、IL1RN、IL18R1）。在比较活跃和不活跃的 RA 时，上调的 TLR2、TLR4、TLR6 和 TLR8 和下调的 TLR10（P<0.04）表达与疾病活动度相关。
我们对全面固有基因谱的研究以及多变量分析揭示了 RA 患者固有特征的一定异质性。从固有特征的多样性中阐明的 RA 异质性是否会影响疾病过程和治疗反应，值得进一步研究。
