Circulating interferon-α2 levels are increased in the majority of patients with systemic lupus erythematosus and are associated with disease activity and multiple cytokine activation

Circulating interferon-α2 levels are increased in the majority of patients with systemic lupus erythematosus and are associated with disease activity and multiple cytokine activation
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DOI:
10.1177/0961203312468964
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发表时间:
2013-02-01
期刊:
影响因子:
2.6
通讯作者:
Nossent, J. C.
Nossent, J. C.
中科院分区:
医学4区
文献类型:
--
作者:
Becker-Merok, A.;Ostli-Eilersten, G.;Nossent, J. C.

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干扰素(IFN)调节因子基因的突变以及I型IFN对IFN诱导的特定基因表达的生物活性与系统性红斑狼疮(SLE)的各个方面有关。由于现有ELISA检测方法的敏感性有限,尚未对SLE患者循环中ifn - α水平进行广泛研究。我们进行了一项横断面病例对照研究,通过高灵敏度的液相多重磁头测定法测量循环中ifn - α 2的水平,并研究了ifn - α 2与SLE患者自身抗体谱、临床疾病活动性和炎症细胞因子水平的关系(n = 87)。在健康对照(n = 27)中,用几何平均值+ 2SD确定的截止水平检测储存血清中的细胞因子水平。与ifn - α 2正常的患者(中位数1,范围3,p < 0.001)相比,64%的SLE患者ifn - α 2水平升高,这些患者表现出更多的肾脏疾病和更高的疾病活动性(p = 0.06),并且活化细胞因子的总数显著增加(中位数4.5,范围7)。因此,溶液相微珠试验确定了三分之二长期SLE患者中ifn - α 2水平升高。与临床疾病和多种炎症细胞因子激活的关联支持ifn - α 2在很大一部分SLE患者的疾病延续中的作用。狼疮(2013)22,155-163。
Mutations in interferon (IFN) regulatory factor genes and the biological activity of type I IFN on expression of specific genes that are induced by IFN have been associated with various aspects of systemic lupus erythematosus (SLE). Circulating levels of IFN-alpha in SLE has not been extensively studied because of limited sensitivity of available ELISA assays. We performed a cross-sectional case-control study where circulating levels of IFN-alpha 2 were measured by a highly sensitive, solution phase multiplex magnetized bead assay and investigated the relation of IFN-alpha 2 with autoantibody profiles, clinical disease activity and levels of inflammatory cytokines in SLE patients (n = 87). Cytokine levels were determined on stored sera aliquots with cut-off levels determined by the geometric mean + 2SD in healthy controls (n = 27). IFN-alpha 2 levels were increased in 64% of SLE patients, who displayed more renal disease and higher disease activity (p = 0.06) and had a significantly higher sum of activated cytokines (median 4.5, range 7) compared to patients with normal IFN-alpha 2 (median one, range 3; p < 0.001). Solution phase micro-bead assay thus identified increased IFN-alpha 2 levels in two-thirds of SLE patients with longstanding disease. The association with clinical disease and activation of multiple inflammatory cytokines supports a role for IFN-alpha 2 in disease perpetuation in a large subset of SLE patients. Lupus (2013) 22, 155-163.