Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Front Immunol. 2022 Jun 10;13:866035. doi: 10.3389/fimmu.2022.866035. eCollection 2022.
Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by asthma-like attacks in its early stage, which is easily misdiagnosed as severe asthma. Therefore, new biomarkers for the early diagnosis of EGPA are needed, especially for differentiating the diagnosis of asthma.
To identify serum biomarkers that can be used for early diagnosis of EGPA and to distinguish EGPA from severe asthma.
Data-independent acquisition (DIA) analysis was performed to identify 45 healthy controls (HC), severe asthma (S-A), and EGPA patients in a cohort to screen biomarkers for early diagnosis of EGPA and to differentiate asthma diagnosis. Subsequently, parallel reaction monitoring (PRM) analysis was applied to a validation cohort of 71 HC, S-A, and EGPA patients.
Four candidate biomarkers were identified from DIA and PRM analysis-i.e., serum amyloid A1 (SAA1), fibrinogen-α (FGA), and serum amyloid P component (SAP)-and were upregulated in the EGPA group, while cholesteryl ester transfer protein (CETP) was downregulated in the EGPA group compared with the S-A group. Receiver operating characteristics analysis shows that, as biomarkers for early diagnosis of EGPA, the combination of SAA1, FGA, and SAP has an area under the curve (AUC) of 0.947, a sensitivity of 82.35%, and a specificity of 100%. The combination of SAA1, FGA, SAP, and CETP as biomarkers for differential diagnosis of asthma had an AUC of 0.921, a sensitivity of 78.13%, and a specificity of 100%, which were all larger than single markers. Moreover, SAA1, FGA, and SAP were positively and CETP was negatively correlated with eosinophil count.
DIA-PRM combined analysis screened and validated four previously unexplored but potentially useful biomarkers for early diagnosis of EGPA and differential diagnosis of asthma.
嗜酸性肉芽肿性多血管炎（EGPA）的特征是早期有哮喘样发作，容易误诊为严重哮喘。因此，需要新的生物标志物用于 EGPA 的早期诊断，特别是用于区分哮喘的诊断。
确定可用于 EGPA 早期诊断并区分 EGPA 与严重哮喘的血清生物标志物。
对队列中的 45 名健康对照（HC）、严重哮喘（S-A）和 EGPA 患者进行数据非依赖性采集（DIA）分析，以筛选用于 EGPA 早期诊断和区分哮喘诊断的生物标志物。随后，对 71 名 HC、S-A 和 EGPA 患者的验证队列进行平行反应监测（PRM）分析。
从 DIA 和 PRM 分析中鉴定出 4 种候选生物标志物-血清淀粉样蛋白 A1（SAA1）、纤维蛋白原-α（FGA）和血清淀粉样蛋白 P 成分（SAP）-在 EGPA 组中上调，而胆固醇酯转移蛋白（CETP）在 EGPA 组中下调与 S-A 组相比。受试者工作特征分析表明，作为 EGPA 早期诊断的生物标志物，SAA1、FGA 和 SAP 的组合具有 0.947 的曲线下面积（AUC）、82.35%的灵敏度和 100%的特异性。SAA1、FGA、SAP 和 CETP 作为哮喘鉴别诊断的生物标志物组合具有 0.921 的 AUC、78.13%的灵敏度和 100%的特异性，均大于单个标志物。此外，SAA1、FGA 和 SAP 呈正相关，而 CETP 呈负相关与嗜酸性粒细胞计数相关。
DIA-PRM 联合分析筛选和验证了四个以前未探索但可能对 EGPA 早期诊断和哮喘鉴别诊断有用的生物标志物。
