Unlike three other newly identified EGPA biomarkers, CETP is selectively downregulated and negatively correlates with eosinophil count, aiding diagnosis versus severe asthma (Front Immunol 2022)

Original title: Serum Proteomic Analysis Identifies SAA1, FGA, SAP, and CETP as New Biomarkers for Eosinophilic Granulomatosis With Polyangiitis

Front Immunol · 1 January 2022 · 6

Xiao J, Lu S, Wang X, Liang M, Dong C, Zhang X, Qiu M, Ou C, Zeng X, Lan Y, Hu L, Tan L et al.

Eosinophilic granulomatosis with polyangiitis (EGPA) presents with asthma-like attacks and is easily misdiagnosed as severe asthma, so new early-diagnosis biomarkers are needed. Data-independent acquisition (DIA) proteomics screened biomarkers in 45 healthy controls, severe asthma and EGPA patients, with parallel reaction monitoring (PRM) validating findings in 71 further patients. Four candidate biomarkers were identified: serum amyloid A1 (SAA1), fibrinogen-alpha (FGA) and serum amyloid P component (SAP) were upregulated in EGPA, while cholesteryl ester transfer protein (CETP) was downregulated in EGPA compared with severe asthma. Combining SAA1, FGA and SAP gave an AUC of 0.947 (82.35% sensitivity, 100% specificity) for early EGPA diagnosis, while adding CETP gave an AUC of 0.921 (78.13% sensitivity, 100% specificity) for differentiating EGPA from severe asthma. SAA1, FGA and SAP correlated positively, and CETP negatively, with eosinophil count.

Original abstract

Background: 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.

Objectives: To identify serum biomarkers that can be used for early diagnosis of EGPA and to distinguish EGPA from severe asthma.

Method: 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.

Result: 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.

Conclusion: DIA-PRM combined analysis screened and validated four previously unexplored but potentially useful biomarkers for early diagnosis of EGPA and differential diagnosis of asthma.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.