Open AccessIncreased mast cell activation in eosinophilic chronic obstructive pulmonary disease
Author(s) -
Higham Andrew,
Dungwa Josiah,
Pham TuyetHang,
McCrae Christopher,
Singh Dave
Publication year - 2022
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1002/cti2.1417
Subject(s) - eosinophil , copd , mast cell , medicine , sputum , chymase , immunology , pathology , inflammation , tryptase , eosinophilic , biopsy , interleukin 5 , eosinophilic esophagitis , eosinophilia , asthma , disease , interleukin , cytokine , tuberculosis
Objectives A subset of chronic obstructive pulmonary disease (COPD) patients have increased numbers of airway eosinophils associated with elevated markers of T2 inflammation. This analysis focussed on mast cell counts and mast cell‐related gene expression in COPD patients with higher vs lower eosinophil counts. Methods We investigated gene expression of tryptase ( TPSAB1 ), carboxypeptidase A3 (CPA3 ), chymase ( CMA1 ) and two mast cell specific gene signatures; a bronchial biopsy signature (MC bb ) and an IgE signature (MC IgE ) using sputum cells and bronchial epithelial brushings. Gene expression analysis was conducted by RNA‐sequencing. We also examined bronchial biopsy mast cell numbers by immunohistochemistry. Results There was increased expression of TPSAB1, CPA3 and MC bb in eosinophil high than in eosinophil low COPD patients in sputum cells and bronchial epithelial brushings (fold change differences 1.21 and 1.28, respectively, P < 0.01). Mast cell gene expression was associated with markers of T2 and eosinophilic inflammation ( IL13, CLCA1, CST1, CCL26 , eosinophil counts in sputum and bronchial mucosa; rho = 0.4–0.8; P < 0.05). There was no difference in MC IgE gene expression between groups. There was no difference in the total number of bronchial biopsy mast cells between groups. Conclusion These results demonstrate that eosinophilic inflammation is associated with altered mast cell characteristics in COPD patients, implicating mast cells as a component of T2 inflammation present in a subset of COPD patients.