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Galectin-3 levels in children with cystic fibrosis

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Abstract

Cystic fibrosis (CF) is a multisystemic disease in which airway obstruction, infection, and inflammation play a critical role in the pathogenesis and progression of CF lung disease. The carbohydrate-binding protein Galectin-3 is increased in several inflammatory and fibrotic diseases and has recently been forwarded as a biomarker in these diseases. We aimed to define the role of serum Galectin-3 in children with CF by comparison with healthy subjects. This is a cross-sectional, case–control study. 143 CF and 30 healthy subjects were enrolled in the study. Peripheral blood and sputum concentrations of Galectins-3, interleukin (IL)-17A, IL-8, and neutrophil elastase (NE) were determined with commercial ELISA kits. There was no significant difference between the groups in age and gender (p = 0.592, p = 0.613, respectively). Serum Galectin-3 and NE concentrations were higher in the patient group than in healthy controls (p = 0.002, p < 0.001, respectively). There were no significant differences between groups according to IL-17A and IL-8 concentrations. Serum Galectin-3 was correlated with age (r = 0.289, p < 0.001) and body mass index (BMI) (r = 0.493, p < 0.001) in children with CF. Sputum Galectin-3 levels are negatively correlated with percent predictive forced expiratory volume in 1 s (FEV1) (r =  − 0.297, p = 0.029), FEV1 z-score, (r =  − 0.316, p = 0.020), percent predictive forced vital capacity (FVC) (r =  − 0.347, p = 0.010), and FVC z-score (r =  − 0.373, p = 0.006).

   Conclusion: The study shows that serum Galectin-3 levels increased in clinically stable CF patients, and serum Galectin-3 response may depend on age, gender, and BMI. The sputum Galectin-3 was found to be negatively correlated with patients’ lung functions.

What is known:

• Galectin-3 is a key regulator of chronic inflammation in the lung, liver, kidney, and tumor microenvironment.

What is new:

• Children with cystic fibrosis (CF) have higher serum Galectin-3 concentrations than healthy children.

• Serum Galectin-3 expression influenced by age, BMI, and gender in children with CF.

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Abbreviations

CF:

Cystic fibrosis

CFTR:

Cystic Fibrosis Transmembrane Conductance Regulator

NE:

Neutrophil elastase

IL-17A:

Interleukin-17A

IL8:

Interleukin-8

ESR:

Erythrocyte sedimentation rate

CRP:

C-reactive protein

FEV1:

Forced expiratory volume in 1 s

FVC:

Forced vital capacity

FEF25-75:

Forced expiratory flow at 25–75% of the pulmonary volume

References

  1. Shteinberg M, Haq IJ, Polineni D, Davies JC (2021) Cystic fibrosis. Lancet 397:2195–2211. https://doi.org/10.1016/S0140-6736(20)32542-3

    Article  CAS  PubMed  Google Scholar 

  2. Nichols DP, Chmiel JF (2015) Inflammation and its genesis in cystic fibrosis. Pediatr Pulmonol 50(Suppl 40):S39-56. https://doi.org/10.1002/ppul.23242

    Article  PubMed  Google Scholar 

  3. McElvaney NG, Proteases CRG, lung injury. In: Crystal RG, West JB, Weibel ER, Barnes PJ, (eds) (1997) The lung: scientific foundations. Lippincott-Raven, Philadelphia, PA, pp 2205–2218

    Google Scholar 

  4. Stockley RA (1995) Role of inflammation in respiratory tract infections. Am J Med 99(6B):8S-13S. https://doi.org/10.1016/s0002-9343(99)80304-0

    Article  CAS  PubMed  Google Scholar 

  5. Chen K, Eddens T, Trevejo-Nunez G et al (2016) IL-17 receptor signaling in the lung epithelium is required for mucosal chemokine gradients and pulmonary host defense against K. pneumoniae. Cell Host Microbe 20:596–605. https://doi.org/10.1016/j.chom.2016.10.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hagner M, Albrecht M, Guerra M et al (2021) IL-17A from innate and adaptive lymphocytes contributes to inflammation and damage in cystic fibrosis lung disease. Eur Respir J 57:1900716. https://doi.org/10.1183/13993003.00716-2019

    Article  CAS  PubMed  Google Scholar 

  7. Tan HL, Regamey N, Brown S, Bush A, Lloyd CM, Davies JC (2011) The Th17 pathway in cystic fibrosis lung disease. Am J Respir Crit Care Med 184(2):252–258. https://doi.org/10.1164/rccm.201102-0236OC

    Article  CAS  PubMed  Google Scholar 

  8. Johannes L, Jacob R, Leffler H (2018) Galectins at a glance. J Cell Sci 131(9):jcs.208884. https://doi.org/10.1242/jcs.208884

    Article  CAS  Google Scholar 

  9. Sciacchitano S, Lavra L, Morgante A et al (2018) Galectin-3: one molecule for an alphabet of diseases, from A to Z. Int J Mol Sci 19(2):379. https://doi.org/10.3390/ijms19020379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ruvolo PP (2016) Galectin 3 as a guardian of the tumor microenvironment. Biochim Biophys Acta 1863(3):427–437. https://doi.org/10.1016/j.bbamcr.2015.08.008

    Article  CAS  PubMed  Google Scholar 

  11. Pugliese G (2008) Do advanced glycation end products contribute to the development of long-term diabetic complications? Nutr Metab Cardiovasc Dis 18:457–460. https://doi.org/10.1016/j.numecd.2008.06.006

    Article  CAS  PubMed  Google Scholar 

  12. Gonz΄alez GE, Cassaglia P, Truant SN (2014) Galectin-3 is essential for early wound healing and ventricular remodelling after myocardial infarction in mice. Int J Cardiol 176:1423–1425. https://doi.org/10.1016/j.ijcard.2014.08.011

    Article  Google Scholar 

  13. Arsenijevic A, Stojanovic B, Milovanovic J, Arsenijevic D, Arsenijevic N, Milovanovic M (2020) Galectin-3 in inflammasome activation and primary biliary cholangitis development. Int J Mol Sci 21:5097. https://doi.org/10.3390/ijms21145097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Han X, Zhang S, Chen Z et al (2020) Cardiac biomarkers of heart failure in chronic kidney disease. Clin Chim Acta 510:298–310. https://doi.org/10.1016/j.cca.2020.07.040

    Article  CAS  PubMed  Google Scholar 

  15. Fort-Gallifa I, Hernández-Aguilera A, García-Heredia A et al (2017) Galectin-3 in peripheral artery disease Relationships with markers of oxidative stress and inflammation. Int J Mol Sci 18:973. https://doi.org/10.3390/ijms18050973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Bouvet GF, Bulka O, Coriati A et al (2021) Peripheral blood mononuclear cell response to YKL-40 and Galectin-3 in cystic fibrosis. Cytokine 146:155635. https://doi.org/10.1016/j.cyto.2021.155635

    Article  CAS  PubMed  Google Scholar 

  17. Rosenstein BJ, Cutting GR (1998) The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J Pediatr 132:589–595. https://doi.org/10.1016/s0022-3476(98)70344-0

    Article  CAS  PubMed  Google Scholar 

  18. Cystic Fibrosis Mutation Database. http://www.genet.sickkids.on.ca/cftr/Home.html. Accessed 5 Mar 2023

  19. Lee TWR, Brownlee KG, Conway SP et al (2003) Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros 2(1):29–34. https://doi.org/10.1016/S1569-1993(02)00141-8

    Article  PubMed  Google Scholar 

  20. Miller MR, Hankinson J, Brusasco V et al (2005) Standardization of spirometry. Eur Respir J 26(2):319–338. https://doi.org/10.1183/09031936.05.00034805

    Article  CAS  PubMed  Google Scholar 

  21. Quanjer PH, Stanojevic S, Cole TJ et al (2012) Multi-ethnic reference values for spirometry for the 3–95-yr age range: the global lung function 2012 equations. Eur Respir J 40(6):1324–1343. https://doi.org/10.1183/09031936.00080312

    Article  PubMed  PubMed Central  Google Scholar 

  22. Schloerke B, Cook D, Larmarange J (2021) GGally: extension to ‘ggplot2’. R package version 2.1.2. https://CRAN.R-project.org/package=GGally

  23. Hector A, Kormann MS, Mack I et al (2011) The chitinase-like protein YKL-40 modulates cystic fibrosis lung disease. PLoS ONE 6(9):e24399. https://doi.org/10.1371/journal.pone.0024399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Leonardi S, Parisi GF, Capizzi A et al (2016) YKL-40 as marker of severe lung disease in cystic fibrosis patients. J Cyst Fibros 15(5):583–586. https://doi.org/10.1016/j.jcf.2015.12.020

    Article  CAS  PubMed  Google Scholar 

  25. Ghorban Movahed M, Abdi Ali A, Ghazanfari T, Modaresi M (2022) Cytokine patterns in cystic fibrosis patients with different microbial infections in oropharyngeal samples. Cytokine 160:156038. https://doi.org/10.1016/j.cyto.2022.156038

    Article  CAS  PubMed  Google Scholar 

  26. Ezzat MH, El-Gammasy TM, Shaheen KY, Osman AO (2011) Elevated production of galectin-3 is correlated with juvenile idiopathic arthritis disease activity, severity, and progression. Int J Rheum Dis 14(4):345–352. https://doi.org/10.1111/j.1756-185X.2011.01632.x

    Article  PubMed  Google Scholar 

  27. Dong R, Zhang M, Hu Q et al (2018) Galectin-3 as a novel biomarker for disease diagnosis and a target for therapy. Int J Mol Med 41(2):599–614. https://doi.org/10.3892/ijmm.2017.3311

    Article  CAS  PubMed  Google Scholar 

  28. Caselli C, Ragusa R, Prontera C et al (2016) Distribution of circulating cardiac biomarkers in healthy children: from birth through adulthood. Biomark Med 10(4):357–365. https://doi.org/10.2217/mm-2015-0044

    Article  CAS  PubMed  Google Scholar 

  29. Pang J, Nguyen VT, Rhodes DH, Sullivan ME, Braunschweig C, Fantuzzi G (2016) Relationship of galectin-3 with obesity, IL-6, and CRP in women. J Endocrinol Invest 39(12):1435–1443. https://doi.org/10.1007/s40618-016-0515-8

    Article  CAS  PubMed  Google Scholar 

  30. Zhen S, Ma Y, Han Y, Zhao Z, Yang X, Wen D (2021) Serum galectin-3BP as a novel marker of obesity and metabolic syndrome in Chinese adolescents. BMJ Open Diabetes Res Care 9(1):e001894. https://doi.org/10.1136/bmjdrc-2020-001894

    Article  PubMed  PubMed Central  Google Scholar 

  31. Suthahar N, Lau ES, Blaha MJ et al (2020) Sex-specific associations of cardiovascular risk factors and biomarkers with incident heart failure. J Am Coll Cardiol 76(12):1455–1465. https://doi.org/10.1016/j.jacc.2020.07.044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Khadeja Bi A, Santhosh V, Sigamani K (2022) Levels of Galectin-3 in chronic heart failure: a case-control study. Cureus 14(8):e28310. https://doi.org/10.7759/cureus.28310

    Article  PubMed  PubMed Central  Google Scholar 

  33. de Boer RA, van Veldhuisen DJ, Gansevoort RT et al (2012) The fibrosis marker galectin-3 and outcome in the general population. J Intern Med 272:55–64. https://doi.org/10.1111/j.1365-2796.2011.02476.x

    Article  CAS  PubMed  Google Scholar 

  34. Ho JE, Gao W, Levy D et al (2016) Galectin-3 is associated with restrictive lung disease and interstitial lung abnormalities. Am J Respir Crit Care Med 194(1):77–83. https://doi.org/10.1164/rccm.201509-1753OC

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. d’Alessandro M, De Vita E, Bergantini L et al (2020) Galactin-1, 3 and 9: potential biomarkers in idiopathic pulmonary fibrosis and other interstitial lung diseases. Respir Physiol Neurobiol 282:103546. https://doi.org/10.1016/j.resp.2020.103546

    Article  CAS  PubMed  Google Scholar 

  36. d’Alessandro M, Bergantini L, Fossi A et al (2021) The role of galectins in chronic lung allograft dysfunction. Lung 199(3):281–288. https://doi.org/10.1007/s00408-021-00449-3

    Article  PubMed  PubMed Central  Google Scholar 

  37. Feng W, Wu X, Li S et al (2017) Association of serum Galectin-3 with the acute exacerbation of chronic obstructive pulmonary disease. Med Sci Monit 23:4612–4618. https://doi.org/10.12659/msm.903472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the Department of Pediatric Allergy, especially Prof. Dr. Özge Uysal and Prof. Dr. Umit Murat Sahiner, for hosting the centrifugation of the study samples.

Funding

This project was funded by the Hacettepe University Scientific Research Project (no. TSA‐2021‐19526).

Author information

Authors and Affiliations

  1. Department of Pediatric Pulmonology, Ankara Bilkent City Hospital, Ankara, Turkey

    Dilber Ademhan Tural

  2. Department of Pediatric Pulmonology, School of Medicine, Hacettepe University, Ihsan Dogramaci Children’s Hospital, Ankara, Turkey

    Nagehan Emiralioglu, Didem Alboga, Beste Ozsezen, Halime Nayir Buyuksahin, Ismail Guzelkas, Birce Sunman, Ebru Yalcin, Deniz Dogru, Nural Kiper & Ugur Ozcelik

  3. Department of Sport Medicine, Hacettepe University, Ankara, Turkey

    Senay Akin, Irem Gungor & Ali Haydar Demirel

  4. Department of Biostatistics, Hacettepe University, Ankara, Turkey

    Merve Kasikci

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  1. Dilber Ademhan Tural
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Contributions

All authors meet the requirements for authorship, having contributed significantly to the study. U. Ozcelik, N. Emiralioglu, S. Akin, A.H. Demirel, and D. Ademhan Tural: conceptualization, methodology, formal analysis, investigation, writing—original draft. U. Ozcelik, N. Kiper, D. Dogru, E. Yalcin, S. Akin, A.H. Demirel, D. Ademhan Tural, M. Kasikci, N. Emiralioglu, D. Alboga, B. Ozsezen, B. Sunman, H. Nayir Buyuksahin, I. Guzelkas, and I. Gungor: conceptualization, methodology, writing—review and editing. All authors critically revised the article, approved the final submitted version of the paper, and took responsibility for the work.

Corresponding author

Correspondence to Dilber Ademhan Tural.

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Ethical approval

The study was conducted after approval from the institutional research and ethical committee (GO 21/392) and according to the Helsinki Declaration of Human Rights guidelines.

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The authors declare no competing interests.

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Communicated by Peter de Winter

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Ademhan Tural, D., Emiralioglu, N., Akin, S. et al. Galectin-3 levels in children with cystic fibrosis. Eur J Pediatr 183, 2333–2342 (2024). https://doi.org/10.1007/s00431-024-05479-6

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