Increased expression of Siglec-1 on peripheral blood monocytes and its role in mononuclear cell reactivity to autoantigen in rheumatoid arthritis.

Increased expression of Siglec-1 on peripheral blood monocytes and its role in mononuclear cell reactivity to autoantigen in rheumatoid arthritis.
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Siglec-1 在外周血单核细胞上的表达增加及其在类风湿性关节炎中单核细胞对自身抗原的反应中的作用。

DOI:
10.1093/rheumatology/ket342
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发表时间:
2014-02
期刊:
Rheumatology (Oxford)
影响因子:
--
通讯作者:
Wu, Li-Juan
Wu, Li-Juan
中科院分区:
其他
文献类型:
--
作者:
Li, Chang;Sun, Yi;Zhong, Ren-Qian;Wu, Li-Juan

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目标 Siglec-1在循环单核细胞上的表达升高已在一些炎性和自身免疫性疾病中报道,但其在RA中的表达和作用尚未阐明。本研究的目的是确定Siglec-1在外周血中的表达,并探讨其在RA单核细胞对自身抗原反应性中的作用。 方法 采用流式细胞术和定量RT-PCR方法分别检测42例RA、39例OA、28例SLE患者和42例正常对照者的Siglec-1蛋白和mRNA水平。此外,10例活动性RA患者接受DMARD治疗12周,并在治疗前后评估Siglec-1阳性细胞和28关节DAS(DAS 28)的频率。此外,TNF-α、IFN-γ和II型胶原被用于上调Siglec-1。用有丝分裂原或抗原刺激来自不同组的外周血单个核细胞(PBMC),并测定细胞增殖和细胞因子产生。 结果 RA患者PBMC和单核细胞上Siglec-1的蛋白和mRNA水平显著高于OA患者和健康对照组。PBMC上Siglec-1蛋白的表达与DAS 28、ESR、高敏CRP和IgM-RF呈正相关,与抗CCP抗体无相关性。有趣的是,抗风湿治疗12周后,Siglec-1表达与DAS 28的降低平行降低。此外,TNF-α、IFN-γ和II型胶原可以上调PBMCs中的Siglec-1。当Siglec-1被抗Siglec-1抗体抑制时,RA患者中升高的PBMC增殖和对胶原刺激的促炎细胞因子产生降低。 结论 PBMC和单核细胞中升高的Siglec-1表达可能作为监测RA疾病活动的生物标志物。Siglec-1还可能在RA中刺激淋巴细胞增殖和活化中发挥促炎作用。
OBJECTIVES Elevated expression of Siglec-1 on circulating monocytes has been reported in some inflammatory and autoimmune diseases, but its expression and role in RA has not been elucidated. The aims of this study were to determine the expression of Siglec-1 in peripheral blood and to explore its role in mononuclear cell reactivity to autoantigen in RA. METHODS Siglec-1 protein and mRNA levels in 42 RA patients, 39 OA patients, 28 SLE patients and 42 normal controls were determined by flow cytometry and quantitative RT-PCR, respectively. In addition, 10 patients with active RA received DMARDs for 12 weeks and the frequencies of Siglec-1-positive cells and the 28-joint DAS (DAS28) were assessed before and after therapy. Furthermore, TNF-α, IFN-γ and type II collagen were used to up-regulate Siglec-1. Peripheral blood mononuclear cells (PBMCs) from different groups were stimulated with mitogens or antigens and cell proliferation and cytokine production were determined. RESULTS The protein and mRNA levels of Siglec-1 on PBMCs and monocytes in RA patients were significantly higher than those in OA patients and healthy controls. Moreover, the expression of Siglec-1 protein on PBMCs was positively correlated with DAS28, ESR, high-sensitivity CRP and IgM-RF, but not with anti-CCP antibody. Interestingly, Siglec-1 expression was decreased in parallel with the decrease in the DAS28 after 12 weeks of anti-rheumatic treatment. Furthermore, TNF-α, IFN-γ and type II collagen can up-regulate Siglec-1 in PBMCs. Elevated PBMC proliferation and proinflammatory cytokine production to collagen stimulation in RA patients decreased when Siglec-1 was inhibited by anti-Siglec-1 antibodies. CONCLUSION Elevated Siglec-1 expression in PBMCs and monocytes can potentially serve as a biomarker for monitoring disease activity in RA. Siglec-1 may also play a proinflammatory role in stimulating lymphocyte proliferation and activation in RA.
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