title: Sputum mast cell subtypes relate to eosinophilia and corticosteroid response in asthma.
abstract: 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.
authors.affiliation: Pneumology Group, Dept of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China Center for Asthma and Respiratory Diseases, Dept of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, Australia.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Center for Asthma and Respiratory Diseases, Dept of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, Australia Katherine.baines@newcastle.edu.au.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Baines
authors.affiliation: Pneumology Group, Dept of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
authors.forename: Juan Juan
authors.initials: JJ
authors.lastname: Fu
authors.affiliation: Center for Asthma and Respiratory Diseases, Dept of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, Australia.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Wood
authors.affiliation: Center for Asthma and Respiratory Diseases, Dept of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, Australia.
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Simpson
authors.affiliation: Center for Asthma and Respiratory Diseases, Dept of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, Australia.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: McDonald
authors.affiliation: The Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Cowan
authors.affiliation: The Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: D Robin
authors.initials: DR
authors.lastname: Taylor
authors.affiliation: The Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Jan O
authors.initials: JO
authors.lastname: Cowan
authors.affiliation: Pneumology Group, Dept of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China Center for Asthma and Respiratory Diseases, Dept of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, University of Newcastle, New Lambton, NSW, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D043422:Carboxypeptidases A / Q000378:metabolism; D053818:Chymases / Q000378:metabolism; D004802:Eosinophilia; D004804:Eosinophils / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D008297:Male; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009569:Nitric Oxide / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011446:Prospective Studies; D012044:Regression Analysis; D013183:Sputum / Q000166:cytology*; D053802:Tryptases / Q000378:metabolism; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D009569:Nitric Oxide; C468648:CPA3 protein, human; D043422:Carboxypeptidases A; C509226:CMA1 protein, human; D053818:Chymases; C546348:TPSAB1 protein, human; D053802:Tryptases