The Unit for Clinical Systems Biology, University of Gothenburg, Gothenburg, Sweden.
PLoS One. 2011;6(8):e23563. doi: 10.1371/journal.pone.0023563. Epub 2011 Aug 24.
Glucocorticoids (GCs) play a key role in the treatment of seasonal allergic rhinitis (SAR). However, some patients show a low response to GC treatment. We hypothesized that proteins that correlated to discrimination between symptomatic high and low responders (HR and LR) to GC treatment might be regulated by GCs and therefore suitable as biomarkers for GC treatment.
METHODOLOGY/PRINCIPAL FINDINGS: We identified 953 nasal fluid proteins in symptomatic HR and LR with a LC MS/MS based-quantitative proteomics analysis and performed multivariate analysis to identify a combination of proteins that best separated symptomatic HR and LR. Pathway analysis showed that those proteins were most enriched in the acute phase response pathway. We prioritized candidate biomarkers for GC treatment based on the multivariate and pathway analysis. Next, we tested if those candidate biomarkers differed before and after GC treatment in nasal fluids from 40 patients with SAR using ELISA. Several proteins including ORM (P<0.0001), APOH (P<0.0001), FGA (P<0.01), CTSD (P<0.05) and SERPINB3 (P<0.05) differed significantly before and after GC treatment. Particularly, ORM (P<0.01), FGA (P<0.05) and APOH (P<0.01) that belonged to the acute phase response pathway decreased significantly in HR but not LR before and after GC treatment.
CONCLUSIONS/SIGNIFICANCE: We identified several novel biomarkers for GC treatment response in SAR with combined proteomics, multivariate and pathway analysis. The analytical principles may be generally applicable to identify biomarkers in clinical studies of complex diseases.
糖皮质激素（GCs）在治疗季节性过敏性鼻炎（SAR）中起着关键作用。然而，一些患者对 GC 治疗的反应较低。我们假设与 GC 治疗后症状性高和低反应者（HR 和 LR）区分相关的蛋白质可能受到 GC 的调节，因此可作为 GC 治疗的生物标志物。
方法/主要发现：我们通过基于 LC-MS/MS 的定量蛋白质组学分析鉴定了 953 种鼻液蛋白，用于鉴定症状性 HR 和 LR 中与 GC 治疗相关的蛋白质，并进行多元分析以鉴定最佳区分症状性 HR 和 LR 的蛋白质组合。途径分析表明，这些蛋白质在急性期反应途径中最丰富。我们基于多元和途径分析，为 GC 治疗确定了候选生物标志物。接下来，我们使用 ELISA 测试了 40 名 SAR 患者鼻液中这些候选生物标志物在 GC 治疗前后的差异。包括 ORM（P<0.0001）、APOH（P<0.0001）、FGA（P<0.01）、CTSD（P<0.05）和 SERPINB3（P<0.05）在内的几种蛋白质在 GC 治疗前后差异显著。特别是属于急性期反应途径的 ORM（P<0.01）、FGA（P<0.05）和 APOH（P<0.01）在 HR 中在 GC 治疗前后显著降低，但在 LR 中则没有。
结论/意义：我们通过综合蛋白质组学、多元和途径分析，鉴定了 SAR 中 GC 治疗反应的几种新的生物标志物。该分析原理可能普遍适用于复杂疾病临床研究中的生物标志物的鉴定。
