Table_4_Immune dysregulation is an important factor in the underlying complications in Influenza infection. ApoH, IL-8 and IL-15 as markers of prognosis.pdf

IntroductionInfluenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression.
MethodsWe conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission.
ResultsPatients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71).
DiscussionTherefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF.

引言
流感病毒感染可引发多种临床症状，包括呼吸衰竭（Respiratory Failure, RF）甚至死亡。目前，该病最严重亚型的致病机制尚未完全阐明。本研究旨在评估患者入院时的初始免疫应答及其对感染进展的潜在影响。
方法
本研究针对2017/18及2018/19流感季入住三级医院的流感病毒感染患者开展一项前瞻性观察性研究。采集患者住院期间首份血清样本，检测其免疫标志物、中性粒细胞活化替代标志物，以及血清中脱氧核糖核酸酶I（DNase I）与载脂蛋白-H（Apolipoprotein-H, ApoH）的水平。对所有患者进行随访直至出院或死亡。本研究初始纳入792例患者，从中选取107例预后不良者，并按入院日期匹配建立随机对照组。
结果
预后不良患者的ApoH水平显著降低，而ApoH是一种可同时调控补体与凝血通路的可溶性蛋白。多因素分析显示，血浆ApoH低水平（比值比[Odds Ratio, OR]:5.43; 95%置信区间2.21~13.4）、C反应蛋白高表达（OR:2.73; 95%置信区间1.28~5.4）、高铁蛋白血症（OR:2.83; 95%置信区间1.28~5.4）以及吸烟史（OR:3.41; 95%置信区间1.04~11.16）均与不良预后显著相关。呼吸衰竭（RF）与ApoH低水平独立相关（OR:5.12; 95%置信区间2.02~1.94），而白细胞介素15（Interleukin-15, IL15）高表达则为保护因素（OR:0.30; 95%置信区间0.12~0.71）。
讨论
综上，住院流感患者的早期免疫应答失调与不良预后相关。充足的血浆ApoH水平可对重症流感及RF起到保护作用，而高表达的IL15则可预防RF的发生。