A2M Serves As Promising Biomarker for Chronic Obstructive Pulmonary Disease

Overview

Journal Int J Chron Obstruct Pulmon Dis

Publisher Dove Medical Press

Specialty Pulmonary Medicine

Date 2023 May 1

PMID 37123074

Authors

Xinru Xiao

Wei Cai

Ziqi Ding

Yujia Shi

Liang Fan

Qian Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Chronic obstructive pulmonary disease (COPD) often associated with cigarette smoking. However, increasing evidence suggests that non-smoking COPD is much higher than previously thought. This study aims to identify a nonsmoking COPD biomarker and examined its value in diagnosis and prediction of acute exacerbation.

Methods: A total of 35 stable COPD patients, 70 acute exacerbation chronic obstructive pulmonary disease (AECOPD) patients and 35 healthy control subjects were included. Plasma α 2 macroglobulin (A2M) and matrix metalloproteinase-9 (MMP-9) levels were measured using the enzyme-linked immunosorbent assay (ELISA) method on all participants. Their association with clinical characteristics and lung function parameters were determined by regression analysis. Receiver operating characteristic (ROC) curve was used to determine the diagnostic sensitivity and specificity. Correlation coefficients were evaluated using Pearson's correlation.

Results: Plasma A2M concentration was decreased and MMP-9 concentration, MMP-9/A2M ratio were elevated in stable COPD patients compared with control groups. And MMP-9 expression was significantly higher in AECOPD patients. A2M level was increased in AECOPD patients with infection compared with those without. In addition, there was no statistical difference in A2M levels between smokers and nonsmokers COPD or healthy control subjects. Furthermore, A2M, MMP-9 and MMP-9/A2M were correlated with forced expiratory volume in one second (FEV)%, FEV/ forced vital capacity (FVC), CAT and mMRC score in COPD patients, but had no correlation with fraction of exhaled nitric oxide (FeNO) and concentration of alveolar nitric oxide (CaNO).

Conclusion: A2M is altered in peripheral blood of COPD patients and correlated with severity and infection. Moreover, there was no significant correlation between the change in A2M and smoking, FeNO and CaNO, suggesting A2M may reflect the overall rather than local inflammation in COPD patients and serve as a potential biomarker for nonsmoking COPD patients.

References

Pinto-Plata V, Casanova C, Mullerova H, de Torres J, Corado H, Varo N . Inflammatory and repair serum biomarker pattern: association to clinical outcomes in COPD. Respir Res. 2012; 13:71. PMC: 3493287. DOI: 10.1186/1465-9921-13-71. View

Jindal S, Aggarwal A, Jindal A, Talwar D, Dhar R, Singh N . COPD exacerbation rates are higher in non-smoker patients in India. Int J Tuberc Lung Dis. 2020; 24(12):1272-1278. DOI: 10.5588/ijtld.20.0253. View

Ocakli B, Acarturk E, Aksoy E, Gungor S, Ciyiltepe F, Oztas S . The impact of exposure to biomass smoke versus cigarette smoke on inflammatory markers and pulmonary function parameters in patients with chronic respiratory failure. Int J Chron Obstruct Pulmon Dis. 2018; 13:1261-1267. PMC: 5912365. DOI: 10.2147/COPD.S162658. View

Poller W, Barth J, Voss B . Detection of an alteration of the alpha 2-macroglobulin gene in a patient with chronic lung disease and serum alpha 2-macroglobulin deficiency. Hum Genet. 1989; 83(1):93-6. DOI: 10.1007/BF00274157. View

Ko F, Chan K, Hui D, Goddard J, Shaw J, Reid D . Acute exacerbation of COPD. Respirology. 2016; 21(7):1152-65. PMC: 7169165. DOI: 10.1111/resp.12780. View

Singh D, Agusti A, Anzueto A, Barnes P, Bourbeau J, Celli B . Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J. 2019; 53(5). DOI: 10.1183/13993003.00164-2019. View

Zhou Y, Yao W, Chen P, Kang J, Huang S, Chen B . COPD in Chinese nonsmokers. Eur Respir J. 2009; 33(3):509-18. DOI: 10.1183/09031936.00084408. View

Bchir S, Ben Nasr H, Bouchet S, Benzarti M, Garrouch A, Tabka Z . Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease. J Cell Mol Med. 2016; 21(7):1280-1291. PMC: 5487915. DOI: 10.1111/jcmm.13057. View

Harwood S, Lyngso J, Zarantonello A, Kjoge K, Nielsen P, Andersen G . Structural Investigations of Human A2M Identify a Hollow Native Conformation That Underlies Its Distinctive Protease-Trapping Mechanism. Mol Cell Proteomics. 2021; 20:100090. PMC: 8167298. DOI: 10.1016/j.mcpro.2021.100090. View

10.

. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med. 2017; 5(9):691-706. PMC: 5573769. DOI: 10.1016/S2213-2600(17)30293-X. View

11.

Arbelaez L, Bergmann U, Tuuttila A, Shanbhag V, Stigbrand T . Interaction of matrix metalloproteinases-2 and -9 with pregnancy zone protein and alpha2-macroglobulin. Arch Biochem Biophys. 1997; 347(1):62-8. DOI: 10.1006/abbi.1997.0309. View

12.

Borth W . Alpha 2-macroglobulin, a multifunctional binding protein with targeting characteristics. FASEB J. 1992; 6(15):3345-53. DOI: 10.1096/fasebj.6.15.1281457. View

13.

Demedts I, Brusselle G, Bracke K, Vermaelen K, Pauwels R . Matrix metalloproteinases in asthma and COPD. Curr Opin Pharmacol. 2005; 5(3):257-63. DOI: 10.1016/j.coph.2004.12.005. View

14.

Culpitt S, Rogers D, Traves S, Barnes P, Donnelly L . Sputum matrix metalloproteases: comparison between chronic obstructive pulmonary disease and asthma. Respir Med. 2005; 99(6):703-10. DOI: 10.1016/j.rmed.2004.10.022. View

15.

Loffek S, Schilling O, Franzke C . Series "matrix metalloproteinases in lung health and disease": Biological role of matrix metalloproteinases: a critical balance. Eur Respir J. 2010; 38(1):191-208. DOI: 10.1183/09031936.00146510. View

16.

Salvi S, Barnes P . Chronic obstructive pulmonary disease in non-smokers. Lancet. 2009; 374(9691):733-43. DOI: 10.1016/S0140-6736(09)61303-9. View

17.

Vandooren J, Itoh Y . Alpha-2-Macroglobulin in Inflammation, Immunity and Infections. Front Immunol. 2021; 12:803244. PMC: 8712716. DOI: 10.3389/fimmu.2021.803244. View

18.

Burnett D, Stockley R . Serum and sputum alpha 2 macroglobulin in patients with chronic obstructive airways disease. Thorax. 1981; 36(7):512-6. PMC: 1020433. DOI: 10.1136/thx.36.7.512. View

19.

Pons A, Sauleda J, Noguera A, Pons J, Barcelo B, Fuster A . Decreased macrophage release of TGF-beta and TIMP-1 in chronic obstructive pulmonary disease. Eur Respir J. 2005; 26(1):60-6. DOI: 10.1183/09031936.05.00045504. View

20.

Gilowska I, Kasper L, Bogacz K, Szczegielniak J, Szymasek T, Kasper M . Impact of Matrix Metalloproteinase 9 on COPD Development in Polish Patients: Genetic Polymorphism, Protein Level, and Their Relationship with Lung Function. Biomed Res Int. 2019; 2018:6417415. PMC: 6311264. DOI: 10.1155/2018/6417415. View