A Signature of Aberrant Immune Responsiveness Identifies Myocardial Dysfunction in Rheumatoid Arthritis
A Signature of Aberrant Immune Responsiveness Identifies Myocardial Dysfunction in Rheumatoid Arthritis
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DOI：
10.1002/art.30323
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发表时间：
2011-06-01
影响因子：
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通讯作者：
Gabriel, Sherine E.
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文献类型：
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作者：
Davis, John M., III;Knutson, Keith L.;Gabriel, Sherine E.
Objective.心力衰竭是类风湿关节炎（RA）患者死亡的重要原因。有证据表明，免疫机制有助于心肌损伤和纤维化，导致左心室舒张功能障碍（LVDD）。本研究的目的是通过分析先天性和适应性免疫系统对体外刺激的反应性来识别RA患者LVDD的特征。RA患者（n = 212）前瞻性纳入一个基于人群的队列进行超声心动图，左室功能分为正常，轻度LVDD，或中度至重度LVDD。使用多重免疫测定法分析了血液单核细胞对7种刺激物的刺激或单独在培养基中刺激的17种细胞因子的释放。在调整临床协变量后，使用逻辑回归模型检验多细胞因子免疫反应评分与LVDD之间的相关性。11-细胞因子谱有效地区分了中重度LVDD患者和LV功能正常的患者。在校正血清白细胞介素-6水平、脑钠肽值、糖皮质激素使用以及其他RA特征和LVDD风险因素后，免疫反应评分（范围0-100）与中重度LVDD密切相关（每10单位比值比1.5 [95%置信区间1.2-2.1]）。这项研究的主要发现是异常的全身免疫反应与RA患者的晚期心肌功能障碍有关。免疫反应评分增加的关于LVDD可能性的独特信息保证了未来对其预测未来心肌功能恶化价值的纵向研究。
Objective. Heart failure is an important cause of death in patients with rheumatoid arthritis (RA). Evidence suggests that immune mechanisms contribute to myocardial injury and fibrosis, leading to left ventricular diastolic dysfunction (LVDD). The purpose of this study was to identify a signature of LVDD in patients with RA by analyzing the responsiveness of the innate and adaptive immune systems to stimulation ex vivo.Methods. RA patients (n = 212) enrolled prospectively in a population-based cohort underwent echocardiography, and LV function was classified as normal, mild LVDD, or moderate-to-severe LVDD. The release of 17 cytokines by blood mononuclear cells in response to stimulation with a panel of 7 stimuli or in media alone was analyzed using multiplex immunoassays. Logistic regression models were used to test for associations between a multicytokine immune response score and LVDD, after adjusting for clinical covariates.Results. An 11-cytokine profile effectively differentiated patients with moderate-to-severe LVDD from those with normal LV function. An immune response score (range 0-100) was strongly associated with moderate-to-severe LVDD (odds ratio per 10 units 1.5 [95% confidence interval 1.2-2.1]) after adjusting for serum interleukin-6 levels, brain natriuretic peptide values, and glucocorticoid use, as well as other RA characteristics and LVDD risk factors.Conclusion. The major finding of this study was that aberrant systemic immune responsiveness is associated with advanced myocardial dysfunction in patients with RA. The unique information added by the immune response score concerning the likelihood of LVDD warrants future longitudinal studies of its value in predicting future deterioration in myocardial function.