Background

Allergic bronchopulmonary aspergillosis (ABPA) constantly develops in asthmatics, which has not been fully investigated.

Objectives

This study aimed to investigate serum differentially expressed proteins (DEPs) between ABPA and asthma using the new approach isobaric tags by relative and absolute quantitation (iTRAQ).

Methods

Each 16 serum samples from ABPA or asthmatic subjects were pooled and screened using iTRAQ. After bioinformatic analysis, five candidate DEPs were validated in the enlarged serum samples from additional 21 ABPA, 31 asthmatic and 20 healthy subjects using ELISA. A receiver operating characteristic (ROC) curve was used to estimate the diagnostic power of carnosine dipeptidase 1 (CNDP1).

Results

A total of 29 DEPs were screened out between ABPA and asthmatic groups. Over half of them were enriched in proteolysis and regulation of protein metabolic process. Further verification showed serum levels of immunoglobulin heavy constant gamma 1, α-1-acid glycoprotein 1, corticosteroid-binding globulin and vitronectin were neither differentially altered between ABPA and asthma nor consistent with the proteomic analysis. Only serum CNDP1 was significantly decreased in ABPA patients, compared with asthmatics and healthy controls (P < 0.01 and P < 0.05). The ROC analysis determined 10.73 ng/mL as the cutoff value of CNDP1, which could distinguish ABPA among asthmatics (AUC 0.770, 95%CI 0.632-0.875, P < 0.001).

Conclusions

This study firstly identified serological DEPs between ABPA and asthma using the new technique iTRAQ. Serum CNDP1 might assist the differential diagnosis of ABPA from asthma and serve as a new pathogenetic factor in fungal colonization and sensitization.

中文翻译：

---

变应性支气管肺曲霉病与哮喘血清差异表达蛋白的蛋白质组学分析

背景

过敏性支气管肺曲霉病 (ABPA) 在哮喘患者中不断发展，尚未得到充分研究。

目标

本研究旨在使用通过相对和绝对定量 (iTRAQ) 的新方法同量异位标记来研究 ABPA 和哮喘之间的血清差异表达蛋白 (DEP)。

方法

使用 iTRAQ 对来自 ABPA 或哮喘受试者的每 16 个血清样本进行汇总和筛选。在生物信息学分析之后，使用 ELISA 在来自另外 21 名 ABPA、31 名哮喘患者和 20 名健康受试者的放大血清样品中验证了五个候选 DEP。受试者工作特征 (ROC) 曲线用于估计肌肽二肽酶 1 (CNDP1) 的诊断能力。

结果

在 ABPA 和哮喘组之间共筛选出 29 个 DEP。其中一半以上富含蛋白质水解和蛋白质代谢过程的调节。进一步的验证表明，ABPA 和哮喘之间的免疫球蛋白重常数 γ 1、α-1-酸性糖蛋白 1、皮质类固醇结合球蛋白和玻连蛋白的血清水平既没有差异，也没有与蛋白质组学分析一致。与哮喘患者和健康对照组相比，ABPA 患者仅血清 CNDP1 显着降低（P  < 0.01 和P  < 0.05）。ROC 分析确定 10.73 ng/mL 作为 CNDP1 的临界值，可以区分哮喘患者的 ABPA（AUC 0.770，95%CI 0.632-0.875，P  < 0.001）。

结论

本研究首先使用新技术 iTRAQ 鉴定了 ABPA 和哮喘之间的血清学 DEP。血清 CNDP1 可能有助于 ABPA 与哮喘的鉴别诊断，并作为真菌定植和致敏的新致病因素。