Skip to main content
Top
Published in: Lung 2/2020

01-04-2020 | Cystic Fibrosis | AIRWAY BIOLOGY

Association of Serum TGF-β1 Levels with Different Clinical Phenotypes of Cystic Fibrosis Exacerbation

Authors: Swati Sagwal, Anil Chauhan, Jyotdeep Kaur, Rajendra Prasad, Meenu Singh, Manvi Singh

Published in: Lung | Issue 2/2020

Login to get access

Abstract

Purpose

Cystic Fibrosis (CF) is a multi-organ genetic disorder and Transforming Growth Factor (TGF-β1) is a modifier gene which modulates lung pathology in CF. There is great phenotypic variability among CF patients who even have similar genotype. The aim of the present study was to associate the serum levels of TGF-β1 with several clinical phenotypes of CF.

Methods

The diagnosed cases of CF were recruited and the blood sample was withdrawn at different time points: during exacerbation (n = 26), non-exacerbation (n = 9) and after antibiotic therapy (n = 11). The concentration of the total TGF-β1 in serum was measured with commercial ELISA kit. The ΔF508 mutation was assessed by the Amplification Refractory Mutation System (ARMS-PCR).

Results

The levels of TGF-β1 were increased in exacerbation phase (119.89 ± 29.64 ng/mL), infection with P. aeruginosa (121.8 ± 28.83 ng/mL) and in subjects with ΔF508 mutation (139.2 ± 19.59 ng/mL). The levels of TGF-β1 in CF patients with Allergic Bronchopulmonary Aspergillosis (ABPA) (109.97 ± 27.71 ng/mL) were decreased as compared to CF patients without ABPA (123.55 ± 30.20 ng/mL). It was observed that the serum levels of TGF-β1 were decreased significantly after antibiotic therapy (p < 0.05).

Conclusions

The present study has determined that the serum levels of TGF-β1 vary with the type of infections, ΔF508 CFTR mutation, presence of ABPA and response to therapy.
Literature
1.
go back to reference Boucher RC (2004) New concepts of the pathogenesis of cystic fibrosis lung disease. Eur Respir J 23(1):146–158PubMedCrossRef Boucher RC (2004) New concepts of the pathogenesis of cystic fibrosis lung disease. Eur Respir J 23(1):146–158PubMedCrossRef
2.
go back to reference Kerem E, Corey M, Kerem B et al (1990) The relation between genotype and phenotype in cystic fibrosis—analysis of the most common mutation (ΔF508). N Engl J Med 323(22):1517–1522PubMedCrossRef Kerem E, Corey M, Kerem B et al (1990) The relation between genotype and phenotype in cystic fibrosis—analysis of the most common mutation (ΔF508). N Engl J Med 323(22):1517–1522PubMedCrossRef
3.
go back to reference Drumm ML, Konstan MW, Schluchter MD, Handler A, Pace R, Zou F et al (2005) Genetic modifiers of lung disease in cystic fibrosis. N Engl J Med 353(14):1443–1453PubMedCrossRef Drumm ML, Konstan MW, Schluchter MD, Handler A, Pace R, Zou F et al (2005) Genetic modifiers of lung disease in cystic fibrosis. N Engl J Med 353(14):1443–1453PubMedCrossRef
4.
go back to reference Bremer LA, Blackman SM, Vanscoy LL, McDougal KE, Bowers A, Naughton KM et al (2008) Interaction between a novel TGFB1 haplotype and CFTR genotype is associated with improved lung function in cystic fibrosis. Hum Mol Genet 17(14):2228–2237PubMedPubMedCentralCrossRef Bremer LA, Blackman SM, Vanscoy LL, McDougal KE, Bowers A, Naughton KM et al (2008) Interaction between a novel TGFB1 haplotype and CFTR genotype is associated with improved lung function in cystic fibrosis. Hum Mol Genet 17(14):2228–2237PubMedPubMedCentralCrossRef
5.
go back to reference Magnan A, Frachon I, Rain B, Peuchmaur M, Monti G, Lenot B et al (1994) Transforming growth factor β in normal human lung: preferential location in bronchial epithelial cells. Thorax 49(8):789–792PubMedPubMedCentralCrossRef Magnan A, Frachon I, Rain B, Peuchmaur M, Monti G, Lenot B et al (1994) Transforming growth factor β in normal human lung: preferential location in bronchial epithelial cells. Thorax 49(8):789–792PubMedPubMedCentralCrossRef
7.
go back to reference Arkwright PD, Laurie S, Super M, Pravica V, Schwarz MJ, Webb AK et al (2000) TGF-beta(1) genotype and accelerated decline in lung function of patients with cystic fibrosis. Thorax 55(6):459–462PubMedPubMedCentralCrossRef Arkwright PD, Laurie S, Super M, Pravica V, Schwarz MJ, Webb AK et al (2000) TGF-beta(1) genotype and accelerated decline in lung function of patients with cystic fibrosis. Thorax 55(6):459–462PubMedPubMedCentralCrossRef
8.
go back to reference Haston CK, Hudson TJ (2005) Finding genetic modifiers of cystic fibrosis. N Engl J Med 353(14):1509–1511PubMedCrossRef Haston CK, Hudson TJ (2005) Finding genetic modifiers of cystic fibrosis. N Engl J Med 353(14):1509–1511PubMedCrossRef
9.
go back to reference Harris WT, Muhlebach MS, Oster RA et al (2009) Transforming growth factor-beta(1) inbronchoalveolar lavage fluid from children with cystic fibrosis. Pediatr Pulmonol 44(11):1057–1064PubMedCrossRef Harris WT, Muhlebach MS, Oster RA et al (2009) Transforming growth factor-beta(1) inbronchoalveolar lavage fluid from children with cystic fibrosis. Pediatr Pulmonol 44(11):1057–1064PubMedCrossRef
10.
go back to reference Harris WT, Muhlebach MS, Oster RA, Knowles MR, Clancy JP, Noah TL (2011) Plasma TGF-β(1) in pediatric cystic fibrosis: potential biomarker of lung disease and response to therapy. Pediatric Pulmonol 46(7):688–695CrossRef Harris WT, Muhlebach MS, Oster RA, Knowles MR, Clancy JP, Noah TL (2011) Plasma TGF-β(1) in pediatric cystic fibrosis: potential biomarker of lung disease and response to therapy. Pediatric Pulmonol 46(7):688–695CrossRef
11.
go back to reference Schwarz KB, Rosensweig J, Sharma S, Jones L, Durant M, Potter C, Narkewicz MR (2003) Plasma markers of platelet activation in cystic fibrosis liver and lung disease. J Pediatric Gastroenterol Nutr 37(2):187–191CrossRef Schwarz KB, Rosensweig J, Sharma S, Jones L, Durant M, Potter C, Narkewicz MR (2003) Plasma markers of platelet activation in cystic fibrosis liver and lung disease. J Pediatric Gastroenterol Nutr 37(2):187–191CrossRef
12.
go back to reference Snodgrass SM, Cihil KM, Cornuet PK, Myerburg MM, Swiatecka-Urban A (2013) Tgf-b1 inhibits Cftr biogenesis and prevents functional rescue of ΔF508-Cftr in primary differentiated human bronchial epithelial cells. PLoS ONE 8(5):e63167PubMedPubMedCentralCrossRef Snodgrass SM, Cihil KM, Cornuet PK, Myerburg MM, Swiatecka-Urban A (2013) Tgf-b1 inhibits Cftr biogenesis and prevents functional rescue of ΔF508-Cftr in primary differentiated human bronchial epithelial cells. PLoS ONE 8(5):e63167PubMedPubMedCentralCrossRef
15.
go back to reference Bilton D, Canny G, Conway S et al (2011) Pulmonary exacerbation: towards a definition for use in clinical trials. Report from the EuroCareCF Working Group on outcome parameters in clinical trials. J Cyst Fibros 10:S79–S81PubMedCrossRef Bilton D, Canny G, Conway S et al (2011) Pulmonary exacerbation: towards a definition for use in clinical trials. Report from the EuroCareCF Working Group on outcome parameters in clinical trials. J Cyst Fibros 10:S79–S81PubMedCrossRef
16.
go back to reference Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA et al (2003) Allergic bronchopulmonary aspergillosis in cystic fibrosis—state of the art: cystic fibrosis foundation consensus conference. Clin Infect Dis 37(3):S225–S264PubMedCrossRef Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA et al (2003) Allergic bronchopulmonary aspergillosis in cystic fibrosis—state of the art: cystic fibrosis foundation consensus conference. Clin Infect Dis 37(3):S225–S264PubMedCrossRef
17.
go back to reference Ferrie RM, Schwarz MJ, Robertson NH, (1992) Development, multiplexing and application of ARMS tests for common mutations in the CFTR gene. Am J Hum Genet 5:149–155 Ferrie RM, Schwarz MJ, Robertson NH, (1992) Development, multiplexing and application of ARMS tests for common mutations in the CFTR gene. Am J Hum Genet 5:149–155
18.
go back to reference Eickmeier O, Boom L, Schreiner F, Lentze MJ, NGampolo D, Schubert R, et al (2013) Transforming growth factor β1 genotypes in relation to TGFβ1, interleukin-8, and tumor necrosis factor alpha in induced sputum and blood in cystic fibrosis. Med Inflamm 2013:913135CrossRef Eickmeier O, Boom L, Schreiner F, Lentze MJ, NGampolo D, Schubert R, et al (2013) Transforming growth factor β1 genotypes in relation to TGFβ1, interleukin-8, and tumor necrosis factor alpha in induced sputum and blood in cystic fibrosis. Med Inflamm 2013:913135CrossRef
19.
go back to reference Corvol HBP, Brouard J, Knauer N, Chadelat K, Henrion-Caude A, Flamant C et al (2008) Genetic variations in inflammatory mediators influence lung disease progression in cystic fibrosis. Pediatr Pulmonol 43(12):1224–1232PubMedCrossRef Corvol HBP, Brouard J, Knauer N, Chadelat K, Henrion-Caude A, Flamant C et al (2008) Genetic variations in inflammatory mediators influence lung disease progression in cystic fibrosis. Pediatr Pulmonol 43(12):1224–1232PubMedCrossRef
20.
go back to reference Dawson KP, Frossard PM, Al-Awar B (2001) Disease severity associated with cysticfibrosis mutations deltaF508 and S549R(T–%3eG). East Mediterr Health J 7(6):975–980PubMed Dawson KP, Frossard PM, Al-Awar B (2001) Disease severity associated with cysticfibrosis mutations deltaF508 and S549R(T–%3eG). East Mediterr Health J 7(6):975–980PubMed
21.
go back to reference Mitash N, Mu F, Donovan JE, Myerburg MM, Ranganathan S, Greene CM, Swiatecka-Urban A (2019) Transforming growth factor-β1 selectively recruits microRNAto the RNA-induced silencing complex and degrades CFTR mRNA under permissive conditions in human bronchial epithelial cells. Int J Mol Sci 20(19):4933PubMedCentralCrossRef Mitash N, Mu F, Donovan JE, Myerburg MM, Ranganathan S, Greene CM, Swiatecka-Urban A (2019) Transforming growth factor-β1 selectively recruits microRNAto the RNA-induced silencing complex and degrades CFTR mRNA under permissive conditions in human bronchial epithelial cells. Int J Mol Sci 20(19):4933PubMedCentralCrossRef
22.
go back to reference Knutsen AP et al (2019) T cell cytokine synthesis in cystic fibrosis patients with allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 113(2):S278CrossRef Knutsen AP et al (2019) T cell cytokine synthesis in cystic fibrosis patients with allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 113(2):S278CrossRef
23.
go back to reference Maloney JP, Narasimhan J, Biller J (2019) Decreased TGF-β1 and VEGF release in cystic fibrosis platelets: further evidence for platelet defects in cystic fibrosis. Lung 194(5):791–798CrossRef Maloney JP, Narasimhan J, Biller J (2019) Decreased TGF-β1 and VEGF release in cystic fibrosis platelets: further evidence for platelet defects in cystic fibrosis. Lung 194(5):791–798CrossRef
Metadata
Title
Association of Serum TGF-β1 Levels with Different Clinical Phenotypes of Cystic Fibrosis Exacerbation
Authors
Swati Sagwal
Anil Chauhan
Jyotdeep Kaur
Rajendra Prasad
Meenu Singh
Manvi Singh
Publication date
01-04-2020
Publisher
Springer US
Published in
Lung / Issue 2/2020
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-020-00320-x

Other articles of this Issue 2/2020

Lung 2/2020 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.