Quantitative proteomics profiling of plasma from children with asthma

Ying Zhou; Shougang Kuai; Ruilin Pan; Qingqing Li; Jian Zhang; Xiaohong Gu; Huali Ren; Yubao Cui

doi:10.1016/j.intimp.2023.110249

Quantitative proteomics profiling of plasma from children with asthma

Int Immunopharmacol. 2023 Jun:119:110249. doi: 10.1016/j.intimp.2023.110249. Epub 2023 May 3.

Authors

Ying Zhou¹, Shougang Kuai², Ruilin Pan³, Qingqing Li³, Jian Zhang⁴, Xiaohong Gu⁵, Huali Ren⁶, Yubao Cui⁷

Affiliations

¹ Department of Pediatrics Laboratory, The Affiliated Wuxi Children's Hospital of Jiangnan University, Wuxi 214023, Jiangsu Province, China.
² Department of Clinical Laboratory, Huishan District Hospital, Wuxi 214187, Jiangsu Province, China.
³ Clinical Research Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, Jiangsu Province, China.
⁴ Department of Clinical Laboratory, The Affiliated Wuxi Children's Hospital of Jiangnan University, Wuxi 214023, Jiangsu Province, China.
⁵ Department of Respiratory, The Affiliated Wuxi Children's Hospital of Jiangnan University, Wuxi 214023, Jiangsu Province, China.
⁶ Department of Allergy, State Grid Beijing Electric Power Hospital, Capital Medical University Electric Power Teaching Hospital, Beijing 100073, China. Electronic address: hualirencn@outlook.com.
⁷ Department of Clinical Laboratory, Huishan District Hospital, Wuxi 214187, Jiangsu Province, China. Electronic address: ybcui1975@hotmail.com.

PMID: 37146352
DOI: 10.1016/j.intimp.2023.110249

Abstract

A lack of validated blood diagnostic markers presents an obstacle to asthma control. The present study sought to profile the plasma proteins of children with asthma and to determine potential biomarkers. Plasma samples from children in acute exacerbation (n = 4), in clinical remission (n = 4), and from healthy children (n = 4, control) were analyzed using a tandem mass tag (TMT)-labeling quantitative proteomics and the candidate biomarkers were validated using liquid chromatography-parallel reaction monitoring (PRM)/mass spectrometry (MS) with enzyme-linked immunosorbent assay (ELISA). We identified 347 proteins with differential expression between groups: 125 (50 upregulated, 75 downregulated) between acute exacerbation and control, 142 (72 upregulated, 70 downregulated) between clinical remission and control, and 55 (22 upregulated, 33 downregulated) between acute and remission groups (all between-group fold changes > 1.2; P < 0.05 by Student's t-test). Gene ontology analysis implicated differentially expressed proteins among children with asthma in immune response, the extracellular region, and protein binding. Further, KEGG pathway analysis of differentially expressed proteins identified complement and coagulation cascades and Staphylococcus aureus infection pathways as having the highest protein aggregation. Our analyses of protein interactions identified important node proteins, particularly KRT10. Among 11 differentially expressed proteins, seven proteins (IgHD, IgHG4, AACT, IgHA1, SAA, HBB, and HBA1) were verified through PRM/MS. Protein levels of AACT, IgA, SAA, and HBB were verified through ELISA and may be useful as biomarkers to identify individuals with asthma. In conclusion, our study presents a novel comprehensive analysis of changes in plasma proteins in children with asthma and identifies a panel for accessory diagnosis of pediatric asthma.

Keywords: Asthma; Diagnosis; Parallel reaction monitoring; Quantitative proteomics; Tandem mass tag.

MeSH terms

Biomarkers
Blood Proteins* / metabolism
Child
Chromatography, Liquid / methods
Humans
Proteomics* / methods
Tandem Mass Spectrometry / methods

Substances

Blood Proteins
Biomarkers