Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada.
Department of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, Canada.
Sci Rep. 2019 Nov 20;9(1):17126. doi: 10.1038/s41598-019-53759-1.
Pulmonary exacerbations (PEx) are clinically impactful events for individuals with CF. Unfortunately, many CF individuals with PEx fail to regain their baseline lung function despite treatment. The objective of this study was to use unbiased proteomic technology to identify novel blood protein biomarkers that change following intravenous (IV) antibiotic treatment and to explore if changes correlate with clinical response by the end of treatment. Blood samples from 25 PEx events derived from 22 unique CF adults were collected within 24 hours of hospital admission, day 5, day 10, and IV antibiotic completion. Three-hundred and forty-six blood proteins were evaluated with label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantitative proteomics and immunoassays. Forty-seven plasma proteins changed significantly following 5 days of IV antibiotic treatment (q-value ≤ 0.10). Early change in IGF2R from hospital admission to day 5 correlated with overall change in symptom score (CFRSD-CRISS) by the end of treatment (r = -0.48, p-value = 0.04). Several plasma proteins identified and quantified by label-free LC-MS/MS changed early following treatment with IV antibiotics and many of these proteins are involved in complement activation and inflammatory/immune-related pathways. Early change in IGF2R correlated with symptom response following IV antibiotic treatment and requires further validation as a predictive biomarker of symptom response.
肺部恶化（PEx）是 CF 患者具有临床重大影响的事件。不幸的是，许多患有 PEx 的 CF 患者尽管接受了治疗，但仍未能恢复其基线肺功能。本研究的目的是使用无偏蛋白组学技术鉴定在静脉（IV）抗生素治疗后发生变化的新型血液蛋白生物标志物，并探索这些变化是否与治疗结束时的临床反应相关。在入院后 24 小时内、第 5 天、第 10 天和 IV 抗生素完成时，从 22 名独特的 CF 成人中收集了 25 个 PEx 事件的血液样本。使用无标记液相色谱-串联质谱（LC-MS/MS）定量蛋白质组学和免疫测定法评估了 346 种血液蛋白。在接受 5 天 IV 抗生素治疗后，47 种血浆蛋白发生显著变化（q 值 ≤ 0.10）。从入院到第 5 天的 IGF2R 早期变化与治疗结束时总体症状评分（CFRSD-CRISS）的变化相关（r = -0.48，p 值 = 0.04）。通过无标记 LC-MS/MS 鉴定和定量的几种血浆蛋白在接受 IV 抗生素治疗后早期发生变化，其中许多蛋白参与补体激活和炎症/免疫相关途径。IGF2R 的早期变化与 IV 抗生素治疗后的症状反应相关，需要进一步验证作为症状反应预测生物标志物。
