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Tryptase+ mast cells associate with fibrotic regions in the lungs of idiopathic pulmonary fibrosis patients; a multiplex staining approach

Elena Miranda, Rebecca Dunmore, Doris Rassl, Helen Parfrey, Catherine Overed-Sayer, Arthur Lewis, Lorcan Sherry, Matt Sleeman, Richard May, Deborah Clarke
European Respiratory Journal 2016 48: PA3412; DOI: 10.1183/13993003.congress-2016.PA3412
Elena Miranda
1Pathology, Translational Sciences, MedImmune, Cambridge, United Kingdom
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Rebecca Dunmore
2Respiratory, Inflammation and Allergy, MedImmune, Cambridge, United Kingdom
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Doris Rassl
3Department of Pathology, Papworth Hospital NHS Foundation Trust Papworth, Cambridge, United Kingdom
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Helen Parfrey
4Respiratory Medicine, Papworth Hospital NHSFT, Cambridge, United Kingdom
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Catherine Overed-Sayer
2Respiratory, Inflammation and Allergy, MedImmune, Cambridge, United Kingdom
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Arthur Lewis
1Pathology, Translational Sciences, MedImmune, Cambridge, United Kingdom
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Lorcan Sherry
5Image Analysis, OracleBio, North Lanarkshire, Scotland, United Kingdom
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Matt Sleeman
2Respiratory, Inflammation and Allergy, MedImmune, Cambridge, United Kingdom
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Richard May
2Respiratory, Inflammation and Allergy, MedImmune, Cambridge, United Kingdom
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Deborah Clarke
2Respiratory, Inflammation and Allergy, MedImmune, Cambridge, United Kingdom
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Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease characterised by a progressive decline in lung function and a mean survival of 3 years post-diagnosis. Several studies have documented the presence of mast cells (MC) in the lungs of IPF patients, but despite this association the role MC play in the fibrotic process remains undefined. This study aimed to characterize specific MC phenotypes including chymase+ (MCC), tryptase+ (MCT) and chymase/tryptase+ cells (MCTC) in IPF lung.

Methods: Lung biopsy specimens from IPF patients (n=17) and normal individuals (n=20) obtained from Papworth Hospital underwent dual IHC staining for chymase and tryptase. Samples were analysed using image software analysis algorithm (Indica Labs HALOÒ software) to quantify the MC density per area (mm2) in both IPF and normal lung tissue, and within annotated fibrotic and non-fibrotic areas.

Results: MCC and MCT were significantly increased in the IPF lung (11.24±2.41 and 100.3±19.36/mm2) compared to controls (2.25±0.73 and 24.9±4.98/mm2 respectively; p<0.001) and were associated with fibrotic regions. MCT increased in both non-fibrotic (p=0.03) and fibrotic areas in IPF samples compared to the same regions in normal controls, whereas no difference was observed for MCC or MCTC.

Conclusions: These data demonstrate that MCC, MCT and MCTC are significantly increased in IPF lung compared to normal controls and are associated mainly with fibrotic regions. Furthermore, multiplex IHC combined with image analysis are important technological tools to enable detailed quantification and interpretation of specific cell populations involved in IPF.

  • Idiopathic pulmonary fibrosis
  • Biomarkers
  • Imaging
  • Copyright ©the authors 2016
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Tryptase+ mast cells associate with fibrotic regions in the lungs of idiopathic pulmonary fibrosis patients; a multiplex staining approach
Elena Miranda, Rebecca Dunmore, Doris Rassl, Helen Parfrey, Catherine Overed-Sayer, Arthur Lewis, Lorcan Sherry, Matt Sleeman, Richard May, Deborah Clarke
European Respiratory Journal Sep 2016, 48 (suppl 60) PA3412; DOI: 10.1183/13993003.congress-2016.PA3412

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Tryptase+ mast cells associate with fibrotic regions in the lungs of idiopathic pulmonary fibrosis patients; a multiplex staining approach
Elena Miranda, Rebecca Dunmore, Doris Rassl, Helen Parfrey, Catherine Overed-Sayer, Arthur Lewis, Lorcan Sherry, Matt Sleeman, Richard May, Deborah Clarke
European Respiratory Journal Sep 2016, 48 (suppl 60) PA3412; DOI: 10.1183/13993003.congress-2016.PA3412
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