Differential gene expressions in peripheral blood mononuclear cells between Th2-driven classical asthma and cough variant asthma_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

DU Min ^1,2 ^共 , WEI Wei ³ ^c , ZHOU Guanghong ⁴ , HUANG Jing ¹ , WANG Yuxia ² ,  LONG Huaicong ²

1. North Sichuan Medical College, Nanchong, Sichuan 637000, P. R. China;
2. Geriatric Intensive Care Unit, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, Chengdu, Sichuan 610072, P. R. China;
3. Department of Respiratory and Critical Care Medicine, Anyue County People's Hospital, Anyue, Sichuan 642350, P. R. China;
4. Department of Respiratory and Critical Care Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, Chengdu, Sichuan 610072, P. R. China;

Corresponding author：

LONG Huaicong, Email: longhc69@163.com

Keywords：

Classical asthma; cough variant asthma; differentially expressed genes

DOI：

10.7507/1671-6205.202304060

Video：

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Objective To reveal the differences in gene expression levels between Th2-driven classical asthma (CA) and Th2-driven cough variant asthma (CVA) in order to investigate the pathogenesis of asthma further. Methods Clinical data were collected from asthmatic patients in the Department of Respiratory and Critical Care of Sichuan Provincial People's Hospital from June 1, 2018, to December 31, 2019. The healthy control (HC) group was healthy adults from the physical examination center. Gene expression of peripheral blood mononuclear cells (PBMCs) in the CA group, CVA group, and HC group was determined by full-length transcriptome sequencing. Differential genes were screened by GO, KEGG analysis, and protein-protein interaction (PPI) network analysis. The results of interaction network analysis were visualized by Cytoscape. Finally, the candidate genes were verified by real-time quantitative polymerase chain reaction (RT-PCR). Results A total of 31 patients with asthma were included in the study, including 20 patients in the CA group and 11 patients in the CVA group. According to serum total IgE > 60 IU/mL and fractional exhaled nitric oxide (FeNO) > 40 ppb as the screening condition, 9 cases of Th2-driven CA and 5 cases of Th2-driven CVA were screened for analysis. Gene expression analysis showed 300 differentially expressed genes between the Th2-driven CA group and the Th2-driven CVA group, among which 155 genes were up-regulated, and 145 were down-regulated. GO enrichment analysis showed that differential genes were mainly enriched in drug response, nitrogen compound biosynthesis, cytoplasmic matrix, protein binding, ATP binding, etc. KEGG pathway analysis showed that differential genes were mainly concentrated in 2-oxy-carboxylic acid metabolism and cytotoxic signaling pathways mediated by natural killer cells. PPI analysis revealed extensive protein interactions between different genes. Ten candidate genes were screened for RT-PCR verification and finally found that CLU, GZMB, PPBP, PRF1, PTGS1, and TMSB4X were significantly differentially expressed between the Th2-driven CA group and the Th2-driven CVA group. Conclusions Asthma's occurrence results from the interaction of many genes and pathways. CLU, GZMB, PPBP, PRF1, PTGS1, and TMSB4X genes may be essential in developing Th2-driven CVA to Th2-driven CA.

Citation： DU Min, WEI Wei, ZHOU Guanghong, HUANG Jing, WANG Yuxia, LONG Huaicong. Differential gene expressions in peripheral blood mononuclear cells between Th2-driven classical asthma and cough variant asthma. Chinese Journal of Respiratory and Critical Care Medicine, 2023, 22(6): 395-402. doi: 10.7507/1671-6205.202304060 Copy

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1. Parker MJ. Asthma. Otolaryngol Clin North Am, 2011, 44(3): 667-684.
2. Reddel HK, Bacharier LB, Bateman ED, et al. Global Initiative for Asthma Strategy 2021: executive summary and rationale for key changes. Eur Respir J, 2021, 59(1): 2102730.
3. Lin JT, Wang WY, Chen P, et al. Prevalence and risk factors of asthma in mainland China: the CARE study. Respir Med, 2018, 137: 48-54.
4. Huang KW, Yang T, Xu JY, et al. Prevalence, risk factors, and management of asthma in China: a national cross-sectional study. Lancet, 2019, 394(10196): 407-418.
5. Cardona V, Ansotegui IJ, Ebisawa M, et al. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J, 2020, 13(10): 100472.
6. Matsumoto H, Niimi A, Takemura M, et al. Prognosis of cough variant asthma: a retrospective analysis. J Asthma, 2006, 43(2): 131-135.
7. Todokoro M, Mochizuki H, Tokuyama K, et al. Childhood cough variant asthma and its relationship to classic asthma. Ann Allergy Asthma Immunol, 2003, 90(6): 652-659.
8. Koh YY, Jeong JH, Park Y, et al. Development of wheezing in patients with cough variant asthma during an increase in airway responsiveness. Eur Respir J, 1999, 14(2): 302-308.
9. The Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA), 2018[EB/OL]. http: //www. ginasthma. org/.
10. Li JH, Han R, Wang YB, et al. Diagnostic possibility of the combination of exhaled nitric oxide and blood eosinophil count for eosinophilic asthma. BMC Pulm Med, 2021, 21(1): 259.
11. Agha F, Sadaruddin A, Abbas S, et al. Serum IgE levels in patients with allergic problems and healthy subjects. J Pak Med Assoc, 1997, 47(6): 166-169.
12. 奥马珠单抗治疗过敏性哮喘专家组, 中华医学会呼吸病学分会哮喘学组. 奥马珠单抗治疗过敏性哮喘的中国专家共识. 中华结核和呼吸杂志, 2018, 41(3): 179-185.
13. Bu DC, Luo HT, Huo PP, et al. KOBAS-i: intelligent prioritization and exploratorcy visualization of biological functions for gene enrichment analysis. Nucleic Acids Res, 2021, 49(W1): W317-W325.
14. 中华医学会变态反应分会呼吸过敏学组(筹), 中华医学会呼吸病学分会哮喘学组. 中国过敏性哮喘诊治指南(第一版, 2019年). 中华内科杂志, 2019, 58(9): 636-655.
15. 王志刚, 申改青, 黄玉焕. 咳嗽变异性哮喘患儿外周血miR-138及RUNX3对Th1/Th2平衡的调节作用. 中国当代儿科杂志, 2021, 23(10): 1044-1049.
16. Jackson DJ, Busby J, Pfeffer PE, et al. Characterisation of patients with severe asthma in the UK Severe Asthma Registry in the biologic era. Thorax, 2021, 76(3): 220-227.
17. Taghavi M, Khosravi A, Mortaz E, et al. Role of pathogen-associated molecular patterns (PAMPS) in immune responses to fungal infections. Eur J Pharmacol, 2017, 808: 8-13.
18. Athari SS. Targeting cell signaling in allergic asthma. Signal Transduct Target Ther, 2019, 4: 45.
19. Haspeslagh E, van Helden MJ, Deswarte K, et al. Role of NKp46⁺ natural killer cells in house dust mite-driven asthma. EMBO Mol Med, 2018, 10(4): e8657.
20. Huff T, Müller CS, Otto AM, et al. β-Thymosins, small acidic peptides with multiple functions. Int J Biochem Cell Biol, 2001, 33(3): 205-220.
21. Yang YP. Cancer immunotherapy: harnessing the immune system to battle cancer. J Clin Invest, 2015, 125(9): 3335-3337.
22. Sol IS, Kim YH, Park YA, et al. Relationship between sputum clusterin levels and childhood asthma. Clin Exp Allergy, 2016, 46(5): 688-695.
23. Sobeih AA, Behairy OG, Abd Almonaem ER, et al. Clusterin in atopic and non-atopic childhood asthma. Scand J Clin Lab Invest, 2019, 79(6): 368-371.
24. Song GG, Kim JH, Lee YH. Association between ADAM33 S2 and ST+4 polymorphisms and susceptibility to asthma: a meta-analysis. Gene, 2013, 524(1): 72-78.
25. Hiroyasu S, Zeglinski MR, Zhao HY, et al. Granzyme B inhibition reduces disease severity in autoimmune blistering diseases. Nat Commun, 2021, 12(1): 302.
26. Bolitho P, Voskoboinik I, Trapani JA, et al. Apoptosis induced by the lymphocyte effector molecule perforin. Curr Opin Immunol, 2007, 19(3): 339-347.
27. Tian M, Chen M, Bao YL, et al. Sputum metabolomic profiling of bronchial asthma based on quadruple time-of-flight mass spectrometry. Int J Clin Exp Pathol, 2017, 10(10): 10363-10373.

Chinese Journal of Respiratory and Critical Care Medicine

Differential gene expressions in peripheral blood mononuclear cells between Th2-driven classical asthma and cough variant asthma

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