RT Journal Article
SR Electronic
T1 Sputum mast cell subtypes relate to eosinophilia and corticosteroid response in asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1123
OP 1133
DO 10.1183/13993003.01098-2015
VO 47
IS 4
A1 Gang Wang
A1 Katherine J. Baines
A1 Juan Juan Fu
A1 Lisa G. Wood
A1 Jodie L. Simpson
A1 Vanessa M. McDonald
A1 Douglas C. Cowan
A1 D. Robin Taylor
A1 Jan O. Cowan
A1 Peter G. Gibson
YR 2016
UL http://erj.ersjournals.com/content/47/4/1123.abstract
AB Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear.Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase (TPSAB1), chymase (CMA1) and carboxypeptidase A3 (CPA3)). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50).MCT (n=18) and MCT/CPA3 (mRNA expression of TPSAB1 and CPA3; n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MCT/CPA3 subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identified CPA3 (OR 1.21, p=0.004) rather than TPSAB1 (OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MCT/CPA3 subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment.Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MCT/CPA3 subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness.Mast cell subtypes detected in sputum relate to eosinophilic inflammation and treatment responsiveness in asthma http://ow.ly/UsEIE