Data_Sheet_7_Differential type I and type III interferon expression profiles in rheumatoid and juvenile idiopathic arthritis.PDF

BackgroundThe role of type I and type III interferons (IFNs) in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) is still poorly understood. The objective of this study was to examine the hypothesis that IFN expression profiles in the peripheral blood differ between subsets of arthritic subjects. Multiple type I and type III IFNs were examined in patients with RA and JIA, as well as among subtypes of JIA.
MethodsTreatment-naïve RA and JIA patients were enrolled. Droplet digital PCR was used to measure the expression of type I, II, and III interferons in blood and synovial fluid leukocytes. Dendritic cell subsets were isolated from synovial fluid to examine IFN expression in each subset. Additionally, synovial mononuclear cells and JIA-derived fibroblast-like synoviocytes were stimulated with TNF, IFNγ, and poly(I:C) to examine inducible IFN expression.
ResultsThe predominant type I IFN gene expressed by blood leukocytes was IFNκ and was significantly lower in RA than JIA and controls. Oligoarticular and psoriatic JIA subgroups showed higher IFNκ expression compared to polyarticular JIA and RA. JIA synovial fluid leukocytes expressed abundant IFNγ and type III IFNs (IFNλ1, IFNλ3), with distinct dendritic cell subset contributions. JIA fibroblast-like synoviocytes produced IFNβ, IFNλ1, and IFNλ2 mRNA upon poly(I:C) stimulation.
ConclusionThis study revealed differences in IFN expression patterns in RA and JIA, with notable differences between JIA subtypes. The expression levels of IFNκ, IFNγ, IFNλ1 and IFNλ3 in JIA suggest specific roles in disease pathology, influenced by disease subtype and joint microenvironment. This study contributes to understanding IFN-mediated mechanisms in arthritis, potentially guiding targeted therapeutic strategies.

【背景】I型与III型干扰素（interferon, IFN）在类风湿关节炎（rheumatoid arthritis, RA）及幼年特发性关节炎（juvenile idiopathic arthritis, JIA）中的作用目前仍未被充分阐明。本研究旨在验证这一假说：外周血中的干扰素表达谱在不同亚型的关节炎患者中存在差异。研究对类风湿关节炎、幼年特发性关节炎患者，以及幼年特发性关节炎的不同亚型患者体内的多种I型和III型干扰素进行了检测。
【方法】本研究纳入初治类风湿关节炎与幼年特发性关节炎患者。采用液滴数字PCR（droplet digital PCR）检测血液与滑液白细胞中I型、II型及III型干扰素的表达水平。从滑液中分离树突状细胞亚群，以检测各亚群内的干扰素表达。此外，分别用肿瘤坏死因子（tumor necrosis factor, TNF）、干扰素γ（interferon γ, IFNγ）及聚肌胞苷酸（poly(I:C)）刺激滑膜单个核细胞与幼年特发性关节炎来源的成纤维样滑膜细胞，以检测诱导型干扰素的表达。
【结果】血液白细胞表达的优势I型干扰素基因为IFNκ，类风湿关节炎患者体内该基因的表达水平显著低于幼年特发性关节炎患者与健康对照组。少关节型与银屑病性幼年特发性关节炎亚组的IFNκ表达水平显著高于多关节型幼年特发性关节炎及类风湿关节炎患者。幼年特发性关节炎患者的滑液白细胞可高表达IFNγ与III型干扰素（IFNλ1、IFNλ3），且不同树突状细胞亚群的贡献存在差异。经聚肌胞苷酸刺激后，幼年特发性关节炎来源的成纤维样滑膜细胞可产生IFNβ、IFNλ1及IFNλ2的mRNA。
【结论】本研究揭示了类风湿关节炎与幼年特发性关节炎患者体内干扰素表达模式的差异，且幼年特发性关节炎的不同亚型间亦存在显著差异。幼年特发性关节炎患者体内IFNκ、IFNγ、IFNλ1及IFNλ3的表达水平提示其在疾病病理过程中发挥特定作用，且该作用受疾病亚型与关节微环境的调控。本研究有助于阐明关节炎中干扰素介导的发病机制，或可为靶向治疗策略的研发提供指导。