Increased Complement Factor B and Bb Levels Are Associated with Mortality in Patients with Severe Aortic Stenosis
Increased Complement Factor B and Bb Levels Are Associated with Mortality in Patients with Severe Aortic Stenosis
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DOI：
10.4049/jimmunol.1801244
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发表时间：
2019-10-01
影响因子：
4.4
通讯作者：
Louwe, Mieke C.
中科院分区：
文献类型：
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作者：
Shahini, Negar;Ueland, Thor;Louwe, Mieke C.
炎症参与了主动脉瓣狭窄（AS）的发生和发展。然而，补体系统的作用，在AS先天免疫的关键组成部分，是不清楚的。我们假设循环中补体因子B（FB）是旁路途径的一个重要组成部分，其水平上调并可预测严重症状性AS患者的预后。因此，通过酶免疫测定法分析了3个队列的重度症状性AS和轻度至中度或重度无症状性AS患者（人群1，n = 123;人群2，n = 436;人群3，n = 61）和健康对照患者的FB、Bb和末端补体复合物血浆水平。与对照组相比，有症状的AS患者FB水平显著升高（人群1和人群2分别增加2.9倍和2.8倍）。有症状和无症状AS患者的FB水平相当（人群2和人群3），无症状患者的FB与瓣膜面积呈负相关。群体1和2中的FB水平与终末补体复合物水平和全身炎症的测量（即，CRP）、心脏功能（即，NT-proBNP）和心肌坏死（即，肌钙蛋白T）。校正临床和生化协变量后，高FB水平与死亡率显著相关（风险比1.37; p = 0.028，人群2）。Bb片段的血浆水平显示出与死亡率相关的类似模式。我们的结论是FB和Bb水平升高与症状性AS患者的不良结局相关。无症状患者中FB水平的增加表明FB从疾病的早期阶段就参与其中。
Inflammation is involved in initiation and progression of aortic stenosis (AS). However, the role of the complement system, a crucial component of innate immunity in AS, is unclear. We hypothesized that circulating levels of complement factor B (FB), an important component of the alternative pathway, are upregulated and could predict outcome in patients with severe symptomatic AS. Therefore, plasma levels of FB, Bb, and terminal complement complex were analyzed in three cohorts of patients with severe symptomatic AS and mild-to-moderate or severe asymptomatic AS (population 1, n = 123; population 2, n = 436; population 3, n = 61) and in healthy controls by enzyme immunoassays. Compared with controls, symptomatic AS patients had significantly elevated levels of FB (2.9- and 2.8-fold increase in population 1 and 2, respectively). FB levels in symptomatic and asymptomatic AS patients were comparable (population 2 and 3), and in asymptomatic patients FB correlated inversely with valve area. FB levels in population 1 and 2 correlated with terminal complement complex levels and measures of systemic inflammation (i.e., CRP), cardiac function (i.e., NT-proBNP), and cardiac necrosis (i.e., Troponin T). High FB levels were significantly associated with mortality also after adjusting for clinical and biochemical covariates (hazard ratio 1.37; p = 0.028, population 2). Plasma levels of the Bb fragment showed a similar pattern in relation to mortality. We concluded that elevated levels of FB and Bb are associated with adverse outcome in patients with symptomatic AS. Increased levels of FB in asymptomatic patients suggest the involvement of FB from the early phase of the disease.