Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti-citrulline autoreactivity is associated with up regulation of proinflammatory cytokines
Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti-citrulline autoreactivity is associated with up regulation of proinflammatory cytokines
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DOI：
10.1136/ard.2006.054924
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发表时间：
2007-06-01
影响因子：
27.4
通讯作者：
Robinson, William H.
中科院分区：
文献类型：
--
作者：
Hueber, Wolfgang;Tomooka, Beren H.;Robinson, William H.
目的：通过关节炎抗原微阵列和多重细胞因子检测，鉴定早期类风湿关节炎患者临床相关亚群的外周血自身抗体和细胞因子谱。方法：对56例诊断为类风湿关节炎的患者进行血清检测。在银屑病关节炎（PsA）和强直性脊柱炎患者（n = 21）和健康个体（n = 19）的样本中也测定了细胞因子谱。数据分析采用多重比较的Kruskal-Wallis检验、Dunn调整、线性相关检验、微阵列显著性分析（SAM）和分层聚类软件。结果：不同的抗体谱与表现出高血清水平的肿瘤坏死因子(TNF) α、白细胞介素（IL） 1 β、IL6、IL13、IL15和粒细胞巨噬细胞集落刺激因子的患者亚组相关。在细胞因子“高”亚组的患者中，观察到针对瓜氨酸化表位的自身抗体反应性显著增加。与对照组相比，早期类风湿关节炎患者TNF α、IL1 α、IL12p40和IL13水平升高，趋化因子eotaxin/CCL11、单核细胞趋化蛋白-1和干扰素诱导蛋白10水平升高（p < 0.001）。趋化因子显示出一些最令人印象深刻的差异。PsA/强直性脊柱炎患者中只有IL8/CXCL8浓度较高（p = 0.02）。结论：在早期类风湿关节炎患者中，血中促炎细胞因子水平升高与瓜氨酸化抗原和疾病活动性替代标志物的自身抗体靶向相关。血清自身抗体、细胞因子和趋化因子的蛋白质组学分析可以将早期类风湿关节炎患者分层为分子亚群。
Objectives: To identify peripheral blood autoantibody and cytokine profiles that characterise clinically relevant subgroups of patients with early rheumatoid arthritis using arthritis antigen microarrays and a multiplex cytokine assay.Methods: Serum samples from 56 patients with a diagnosis of rheumatoid arthritis of 'months' duration were tested. Cytokine profiles were also determined in samples from patients with psoriatic arthritis (PsA) and ankylosing spondylitis (n = 21), and from healthy individuals (n = 19). Data were analysed using Kruskal-Wallis test with Dunn's adjustment for multiple comparisons, linear correlation tests, significance analysis of microarrays (SAM) and hierarchical clustering software.Results: Distinct antibody profiles were associated with subgroups of patients who exhibited high serum levels of tumour necrosis factor (TNF) alpha, interleukin (IL) 1 beta, IL6, IL13, IL15 and granulocyte macrophage colony-stimulating factor. Significantly increased autoantibody reactivity against citrullinated epitopes was observed in patients within the cytokine "high'' subgroup. Increased levels of TNF alpha, IL1 alpha, IL12p40 and IL13, and the chemokines eotaxin/CCL11, monocyte chemoattractant protein-1 and interferon-inducible protein 10, were present in early rheumatoid arthritis as compared with controls (p < 0.001). Chemokines showed some of the most impressive differences. Only IL8/CXCL8 concentrations were higher in patients with PsA/ankylosing spondylitis (p = 0.02).Conclusions: Increased blood levels of proinflammatory cytokines are associated with autoantibody targeting of citrullinated antigens and surrogate markers of disease activity in patients with early rheumatoid arthritis. Proteomic analysis of serum autoantibodies, cytokines and chemokines enables stratification of patients with early rheumatoid arthritis into molecular subgroups.