Type I interferon system activation and association with disease manifestations in systemic sclerosis
Type I interferon system activation and association with disease manifestations in systemic sclerosis
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DOI：
10.1136/ard.2009.121400
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发表时间：
2010-07-01
影响因子：
27.4
通讯作者：
Ronnblom, Lars
中科院分区：
文献类型：
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作者：
Eloranta, Maija-Leena;Franck-Larsson, Karin;Ronnblom, Lars
目的研究系统性硬化症（SSc）患者中干扰素自身抗体的存在及其与临床表现的关系，血清干扰素α水平方法用来自SSc患者（n=70）或健康个体（n=30）的血清刺激来自健康供体的外周血单核细胞（PBMC）或纯化的浆细胞样树突状细胞（pDC）。以及坏死或凋亡的细胞物质。IFN α产生和IFN α、IFN诱导蛋白-10（IP-10）/趋化因子的血清水平（C-X-C基序）配体10，单核细胞趋化蛋白-1（MCP-1）/（C-C基序）配体-2（CCL-2），巨噬细胞炎性蛋白-1 α（MIP-1 α）/CCL-3和RANTES/CCL-结果弥漫型和局限型SSc患者血清中均含有干扰素抗体，其与抗核糖核蛋白和抗干燥综合征抗原自身抗体的存在相关。pDC负责IFN α的产生，这需要与Fc γ RII相互作用和内吞作用。IP-10血清水平升高与血管表现相关，如心脏受累（p=0.027）和肺动脉高压（p=0.036）。MCP-1或IFN α血清水平升高与肺纤维化相关（分别为p=0.019和0.048）。手指溃疡，包括数字损失与增加血清IFN α水平（p=0.029）。结论激活的I型IFN系统以前看到的几个其他系统性自身免疫性疾病也存在于SSc，并可能有助于血管病理和影响促纤维化过程。
Objectives To study the presence of interferogenic autoantibodies in systemic sclerosis (SSc) and their correlation with clinical manifestations, serum levels of interferon alpha (IFN alpha) and chemokines of importance in the disease process.Methods Peripheral blood mononuclear cells (PBMCs) or purified plasmacytoid dendritic cells (pDCs) from healthy donors were stimulated with sera from patients with SSc (n=70) or healthy individuals (n=30), together with necrotic or apoptotic cell material. The IFN alpha produced and serum levels of IFN alpha, IFN-inducible protein-10 (IP-10)/chemokine (C-X-C motif) ligand 10, monocyte chemoattractant protein-1 (MCP-1)/(C-C motif) ligand-2 (CCL-2), macrophage inflammatory protein-1 alpha (MIP-1 alpha)/CCL-3 and RANTES/CCL-5 were measured and correlated with the presence of autoantibodies and clinical manifestations in the patients with SSc.Results Sera from both diffuse SSc and limited SSc contained interferogenic antibodies, which correlated with the presence of anti-ribonucleoprotein and anti-Sjogren syndrome antigen autoantibodies. The pDCs were responsible for the IFN alpha production which required interaction with Fc gamma RII and endocytosis. Increased serum levels of IP-10 were associated with vascular manifestations such as cardiac involvement (p=0.027) and pulmonary arterial hypertension (p=0.036). Increased MCP-1 or IFN alpha serum levels were associated with lung fibrosis (p=0.019 and 0.048, respectively). Digital ulcers including digital loss were associated with increased serum levels of IFN alpha (p=0.029).Conclusion An activated type I IFN system previously seen in several other systemic autoimmune diseases is also present in SSc and may contribute to the vascular pathology and affect the profibrotic process.