Skip to main content
Erschienen in: Lung 2/2020

01.04.2020 | AIRWAY BIOLOGY

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

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

Erschienen in: Lung | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

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The diagnosed cases of CF were recruited and the blood sample was withdrawn at different time points: during exacerbation (n = 26), non-exacerbation (n = 9) and after antibiotic therapy (n = 11).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.
Literatur
1.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
Metadaten
Titel
Association of Serum TGF-β1 Levels with Different Clinical Phenotypes of Cystic Fibrosis Exacerbation
verfasst von
Swati Sagwal
Anil Chauhan
Jyotdeep Kaur
Rajendra Prasad
Meenu Singh
Manvi Singh
Publikationsdatum
01.04.2020
Verlag
Springer US
Erschienen in
Lung / Ausgabe 2/2020
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-020-00320-x

Weitere Artikel der Ausgabe 2/2020

Lung 2/2020 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.