Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Mycopathologia Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Knutsen AP. Allergic bronchopulmonary aspergillosis in asthma. Expert Rev Clin Immunol. 2017;13(1):11–4. https://doi.org/10.1080/1744666x.2017.1232620.

    Article  CAS  PubMed  Google Scholar 

  2. Latge JP. Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev. 1999;12(2):310–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. van de Veerdonk FL, Gresnigt MS, Romani L, Netea MG, Latge JP. Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol. 2017;15(11):661–74. https://doi.org/10.1038/nrmicro.2017.90.

    Article  CAS  PubMed  Google Scholar 

  4. Denning DW, Pleuvry A, Cole DC. Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults. Med Mycol. 2013;51(4):361–70. https://doi.org/10.3109/13693786.2012.738312.

    Article  PubMed  Google Scholar 

  5. Sockrider M, Wenzel SE, Castro M, Kulkarni H. What is allergic bronchopulmonary aspergillosis (ABPA)? Am J Respir Crit Care Med. 2014;190(6):P3–4. https://doi.org/10.1164/rccm.1906P3.

    Article  Google Scholar 

  6. Hinson KF, Moon AJ, Plummer NS. Broncho-pulmonary aspergillosis; a review and a report of eight new cases. Thorax. 1952;7(4):317–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mou Y, Ye L, Ye M, Yang D, Jin M. A retrospective study of patients with a delayed diagnosis of allergic bronchopulmonary aspergillosis/allergic bronchopulmonary mycosis. Allergy Asthma Proc. 2014;35(2):192. https://doi.org/10.2500/aap.2014.35.3731.

    Article  Google Scholar 

  8. Lotvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127(2):355–60. https://doi.org/10.1016/j.jaci.2010.11.037.

    Article  PubMed  Google Scholar 

  9. Woolnough KF, Richardson M, Newby C, Craner M, Bourne M, Monteiro W, et al. The relationship between biomarkers of fungal allergy and lung damage in asthma. Clin Exp Allergy. 2017;47(1):48–56. https://doi.org/10.1111/cea.12848.

    Article  CAS  PubMed  Google Scholar 

  10. Agarwal R, Sehgal IS, Dhooria S, Aggarwal AN. Developments in the diagnosis and treatment of allergic bronchopulmonary aspergillosis. Expert Rev Respir Med. 2016;10(12):1317–34. https://doi.org/10.1080/17476348.2016.1249853.

    Article  CAS  PubMed  Google Scholar 

  11. Overton NL, Denning DW, Bowyer P, Simpson A. Genetic susceptibility to allergic bronchopulmonary aspergillosis in asthma: a genetic association study. Allergy Asthma Clin Immunol. 2016;12:47. https://doi.org/10.1186/s13223-016-0152-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Gago S, Overton NLD, Ben-Ghazzi N, Novak-Frazer L, Read ND, Denning DW, et al. Lung colonization by Aspergillus fumigatus is controlled by ZNF77. Nat Commun. 2018;9(1):3835. https://doi.org/10.1038/s41467-018-06148-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kniemeyer O, Ebel F, Kruger T, Bacher P, Scheffold A, Luo T, et al. Immunoproteomics of Aspergillus for the development of biomarkers and immunotherapies. Proteomics Clin Appl. 2016;10(9–10):910–21. https://doi.org/10.1002/prca.201600053.

    Article  CAS  PubMed  Google Scholar 

  14. CSRD ASGo. Guidelines for the prevention and treatment of bronchial asthma. Chin J Tuberc Respir Dis. 2016;39(9):675–97.

    Google Scholar 

  15. Agarwal R, Chakrabarti A, Shah A, Gupta D, Meis JF, Guleria R, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013;43(8):850–73. https://doi.org/10.1111/cea.12141.

    Article  CAS  PubMed  Google Scholar 

  16. Mauri P, Riccio AM, Rossi R, Di Silvestre D, Benazzi L, De Ferrari L, et al. Proteomics of bronchial biopsies: galectin-3 as a predictive biomarker of airway remodelling modulation in omalizumab-treated severe asthma patients. Immunol Lett. 2014;162(1):2–10. https://doi.org/10.1016/j.imlet.2014.08.010.

    Article  CAS  PubMed  Google Scholar 

  17. Bantscheff M, Schirle M, Sweetman G, Rick J, Kuster B. Quantitative mass spectrometry in proteomics: a critical review. Anal Bioanal Chem. 2007;389(4):1017–31. https://doi.org/10.1007/s00216-007-1486-6.

    Article  CAS  PubMed  Google Scholar 

  18. Singh B, Singh S, Asif AR, Oellerich M, Sharma GL. Allergic aspergillosis and the antigens of Aspergillus fumigatus. Curr Protein Pept Sci. 2014;15(5):403–23.

    Article  CAS  PubMed  Google Scholar 

  19. Kauffman HF, Tomee JF, van de Riet MA, Timmerman AJ, Borger P. Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production. J Allergy Clin Immunol. 2000;105(6 Pt 1):1185–93.

    Article  CAS  PubMed  Google Scholar 

  20. Namvar S, Warn P, Farnell E, Bromley M, Fraczek M, Bowyer P, et al. Aspergillus fumigatus proteases, Asp f 5 and Asp f 13, are essential for airway inflammation and remodelling in a murine inhalation model. Clin Exp Allergy. 2015;45(5):982–93. https://doi.org/10.1111/cea.12426.

    Article  CAS  PubMed  Google Scholar 

  21. Basu T, Seyedmousavi S, Sugui JA, Balenga N, Zhao M, Kwon Chung KJ, et al. Aspergillus fumigatus alkaline protease 1 (Alp1/Asp f13) in the airways correlates with asthma severity. J Allergy Clin Immunol. 2018;141(1):423.e42–425.e427. https://doi.org/10.1016/j.jaci.2017.07.034.

    Article  CAS  Google Scholar 

  22. Tay TR, Bosco J, Gillman A, Aumann H, Stirling R, O’Hehir R, et al. Coexisting atopic conditions influence the likelihood of allergic bronchopulmonary aspergillosis in asthma. Ann Allergy Asthma Immunol. 2016;117(1):29e21–32e21. https://doi.org/10.1016/j.anai.2016.04.024.

    Article  Google Scholar 

  23. Kalaiyarasan JAK, Puri M, Tayal D, Singhal R, Sarin R. Prevalence of allergic bronchopulmonary aspergillosis in asthmatic patients: a prospective institutional study. Indian J Tuberc. 2018;65(4):285–9. https://doi.org/10.1016/j.ijtb.2018.04.007.

    Article  CAS  PubMed  Google Scholar 

  24. Agarwal R, Aggarwal AN, Sehgal IS, Dhooria S, Behera D, Chakrabarti A. Utility of IgE (total and Aspergillus fumigatus specific) in monitoring for response and exacerbations in allergic bronchopulmonary aspergillosis. Mycoses. 2016;59(1):1–6. https://doi.org/10.1111/myc.12423.

    Article  CAS  PubMed  Google Scholar 

  25. Lou B, Xu Z, Yang G, Guo C, Zheng S, Lou H, et al. Role of Aspergillus fumigatus-specific IgE in the diagnosis of allergic bronchopulmonary aspergillosis. Int Arch Allergy Immunol. 2019;178(4):338–44. https://doi.org/10.1159/000495365.

    Article  CAS  PubMed  Google Scholar 

  26. Moulder R, Bhosale SD, Goodlett DR, Lahesmaa R. Analysis of the plasma proteome using iTRAQ and TMT-based isobaric labeling. Mass Spectrom Rev. 2018;37(5):583–606. https://doi.org/10.1002/mas.21550.

    Article  CAS  PubMed  Google Scholar 

  27. Toor A, Culibrk L, Singhera GK, Moon K-M, Prudova A, Foster LJ, et al. Transcriptomic and proteomic host response to Aspergillus fumigatus conidia in an air-liquid interface model of human bronchial epithelium. PLoS ONE. 2018;13(12):e0209652. https://doi.org/10.1371/journal.pone.0209652.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Thakur R, Shankar J. Proteome analysis revealed jak/stat signaling and cytoskeleton rearrangement proteins in human lung epithelial cells during interaction with Aspergillus terreus. Curr Signal Transduct Ther. 2019;14(1):55–67. https://doi.org/10.2174/1574362413666180529123513.

    Article  CAS  Google Scholar 

  29. Gustafsson PM, Oxelius V-A, Nilsson S, Kjellman B. Association between Gm allotypes and asthma severity from childhood to young middle age. Respir Med. 2008;102(2):266–72.

    Article  PubMed  Google Scholar 

  30. Liu JY, Wang Y, Wang YZ, Zhu JW, Dai FD. Screening serum differential proteins for childhood asthma at different control levels by isobaric tags for relative and absolute quantification-based proteomic technology. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2017;39(6):817–26. https://doi.org/10.3881/j.issn.1000-503X.2017.06.014.

    Article  PubMed  Google Scholar 

  31. Salazar-Peláez LM, Abraham T, Herrera AM, Correa MA, Ortega JE, Paré PD, et al. Vitronectin expression in the airways of subjects with asthma and chronic obstructive pulmonary disease. PLoS ONE. 2015;10(3):e0119717. https://doi.org/10.1371/journal.pone.0119717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. James B, Milstien S, Spiegel S. ORMDL3 and allergic asthma: from physiology to pathology. J Allergy Clin Immunol. 2019;144(3):634–40. https://doi.org/10.1016/j.jaci.2019.07.023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wu H, Romieu I, Sienra-Monge JJ, Li H, del Rio-Navarro BE, London SJ. Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and childhood asthma. Allergy. 2009;64(4):629–35. https://doi.org/10.1111/j.1398-9995.2008.01912.x.

    Article  CAS  PubMed  Google Scholar 

  34. Arner P, Henjes F, Schwenk JM, Darmanis S, Dahlman I, Iresjo BM, et al. Circulating carnosine dipeptidase 1 associates with weight loss and poor prognosis in gastrointestinal cancer. PLoS ONE. 2015;10(4):e0123566. https://doi.org/10.1371/journal.pone.0123566.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Schwenk JM, Igel U, Neiman M, Langen H, Becker C, Bjartell A, et al. Toward next generation plasma profiling via heat-induced epitope retrieval and array-based assays. Mol Cell Proteomics. 2010;9(11):2497–507. https://doi.org/10.1074/mcp.M110.001560.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yadav AK, Sinha N, Kumar V, Bhansali A, Dutta P, Jha V. Association of CTG repeat polymorphism in carnosine dipeptidase 1 (CNDP1) gene with diabetic nephropathy in north Indians. Indian J Med Res. 2016;144(1):32–7. https://doi.org/10.4103/0971-5916.193280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Dietl A-M, Binder U, Bauer I, Shadkchan Y, Osherov N, Haas H. Arginine auxotrophy affects siderophore biosynthesis and attenuates virulence of Aspergillus fumigatus. Genes (Basel). 2020;11(4):423. https://doi.org/10.3390/genes11040423.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge all the subjects for their participation. This work was supported by grants from the National R&D Program (2016YFC1304000, 2016YFC1304002) and Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02013). In addition, it was also supported by Instrumental Analysis Center of Shenzhen University for providing research instruments.

Author information

Author notes

  1. Hui Cai and Diquan Shuai contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China

    Hui Cai, Xiaomin Xue, Yuqing Mo, Xixi Song, Ling Ye & Meiling Jin

  2. Shenzhen Key Laboratory of Microbiology and Gene Engineering, College of Life Sciences and Oceanography, Shenzhen University, No. 1066 Xueyuan Ave, Nanshan District, Shenzhen, 518055, Guangdong, China

    Diquan Shuai, Shuiming Li, Daiwei Wang & Yun Wang

Authors
  1. Hui Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diquan Shuai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaomin Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuqing Mo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xixi Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ling Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shuiming Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Daiwei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Meiling Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HC and DS performed the experiments and analyzed the data, and HC drafted the writing. XX, YM and XS collected the serum samples and acquired the clinical data. LY, SL and DW provided guidance on experiments and bioinformatic analysis. MJ and YW conceived the ideas and organized this study. All authors have read and approved this final manuscript.

Corresponding authors

Correspondence to Yun Wang or Meiling Jin.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Handling Editor: Vishnu Chaturvedi.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1: Identification of serum proteins from ABPA and asthmatic subjects. (XLSX 91 kb)

11046_2020_506_MOESM2_ESM.xlsx

Supplementary material 2: Gene ontology annotation (biological process) of differentially expressed proteins between ABPA and asthma. (XLSX 179 kb)

11046_2020_506_MOESM3_ESM.xlsx

Supplementary material 3: Gene ontology annotation (cellular component) of differentially expressed proteins between ABPA and asthma. (XLSX 24 kb)

11046_2020_506_MOESM4_ESM.xlsx

Supplementary material 4: Gene ontology annotation (molecular function) of differentially expressed proteins between ABPA and asthma. (XLSX 19 kb)

11046_2020_506_MOESM5_ESM.xlsx

Supplementary material 5: KEGG pathway and enrichment analysis of differentially expressed proteins between ABPA and asthma. (XLSX 11 kb)

11046_2020_506_MOESM6_ESM.xlsx

Supplementary material 6: The protein–protein interaction network of differentially expressed proteins between ABPA and asthma. (XLSX 10 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cai, H., Shuai, D., Xue, X. et al. Proteomic Analysis of Serum Differentially Expressed Proteins Between Allergic Bronchopulmonary Aspergillosis and Asthma. Mycopathologia 186, 1–13 (2021). https://doi.org/10.1007/s11046-020-00506-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11046-020-00506-0

Keywords

Search

Navigation