Proteomic Analysis of Serum Differentially Expressed Proteins Between Allergic Bronchopulmonary Aspergillosis and Asthma

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.