Association of Profoundly Impaired Immune Competence in H1N1v-Infected Patients with a Severe or Fatal Clinical Course
Association of Profoundly Impaired Immune Competence in H1N1v-Infected Patients with a Severe or Fatal Clinical Course
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DOI：
10.1086/655469
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发表时间：
2010-09-01
影响因子：
6.4
通讯作者：
Martini, Federico
中科院分区：
文献类型：
--
作者：
Agrati, Chiara;Gioia, Cristiana;Martini, Federico
背景。甲型h1n1流感大流行的特点是临床病程较轻。然而，一小部分患者因原发性病毒性肺炎或继发性细菌感染而发展为快速进展的病程，在许多情况下，由于呼吸衰竭而导致死亡。本研究的目的是分析免疫应答在甲型h1n1流感临床表现中的作用。比较轻症（n= 22）和重症（n=6）甲型h1n1病毒感染患者T细胞的分化和功能。定量分析血浆细胞因子和趋化因子。来自甲型h1n1病毒感染患者的T细胞表现出严重的临床病程，导致效应细胞分化受损，无法对有丝分裂刺激做出反应。T细胞的能量与严重的急性期感染密切相关，但在能够康复的患者中，T细胞可以恢复。有趣的是，在无能T细胞上发现大量CD95标记物的表达，提示其凋亡相关机制。最后，在流感临床病程较差的患者中发现较低的血浆干扰素- α和单核细胞趋化蛋白-1水平，提示这些细胞因子的产生受损。我们的研究结果表明，宿主免疫能力与h1n1感染临床病程的严重程度之间存在严格的关联。通过监测宿主功能反应，可以及时识别出发生流感相关严重并发症风险增加的患者。
Background. Pandemic A/H1N1v influenza is characterized by a mild clinical course. However, a small subset of patients develops a rapidly progressive course caused by primary viral pneumonia or secondary bacterial infections that, in many cases, lead to death due to respiratory failure. The aim of the present study was to analyze the involvement of the immune response in the clinical presentation of H1N1v influenza.Methods. The differentiation and functional capability of T cells from H1N1v-infected patients presenting with either mild disease (n = 22) or severe or fatal disease (n=6) were compared. Moreover, plasma cytokines and chemokines were quantifiedResults. T cells from H1N1v-infected patients presenting with a severe clinical course resulted in impaired effector cell differentiation and failed to respond to mitogenic stimulation. T cell anergy was strictly associated with a severe acute phase of infection, but T cells could be restored in patients able to recover. Of interest, massive expression of CD95 marker was found on anergic T cells, suggesting an apoptosis-related mechanism. Finally, lower plasma levels of interferon-alpha and monocyte chemoattractant protein-1 were found in patients with a worse clinical course of influenza, suggesting impaired production of these cytokines.Conclusions. Our results show a strict association between host immune competence and the severity of the clinical course of H1N1v infection. By monitoring host functional response, patients with an enhanced risk of developing influenza-associated severe complications could be identified in a timely manner.