Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients

Respiratory Research

Research

Hans Scheers¹  Peter W Hellings²  Ellen Dilissen³  Gudrun Marijsse³  Jan L. Ceuppens³  Sven F. Seys⁴  Dominique M. A. Bullens⁵  Annelies Van Den Bergh⁶  Paul Van den Brande⁶  Pieter C. Goeminne⁷  Lieven J Dupont⁷ 

[1] Department of Public Health and Primary Care, Environmental Health Unit, Lab of pneumology, Leuven, KU, Belgium;ENT department, Leuven, UZ, Belgium;Lab of clinical immunology, Department of Microbiology and Immunology, Herestraat 49/811, 3000, Leuven, KU, Belgium;Lab of clinical immunology, Department of Microbiology and Immunology, Herestraat 49/811, 3000, Leuven, KU, Belgium;Department of Public Health and Primary Care, Environmental Health Unit, Lab of pneumology, Leuven, KU, Belgium;Paediatric department, Leuven, UZ, Belgium;Lab of paediatric immunology, Department of Microbiology and Immunology, Leuven, KU, Belgium;Respiratory department, Leuven, UZ, Belgium;Respiratory department, Leuven, UZ, Belgium;Lab of respiratory disease, and lab of pediatric immunology, Department of Clinical and Experimental Medicine, Leuven, KU, Belgium;

关键词: Airway inflammation;    Type 2 inflammation;    Endotype;    Phenotype;    Precision medicine;   

DOI  :  10.1186/s12931-017-0524-y

 received in 2016-09-09, accepted in 2017-02-17,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAsthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h)2-high and T(h)2-low airway inflammation. Profiling of a broader panel of airway cytokines in large unselected patient cohorts is lacking.MethodsPatients (n = 205) were defined as being “cytokine-low/high” if sputum mRNA expression of a particular cytokine was outside the respective 10th/90th percentile range of the control group (n = 80). Unsupervised hierarchical clustering was used to determine clusters based on sputum cytokine profiles.ResultsHalf of patients (n = 108; 52.6%) had a classical T(h)2-high (“IL-4-, IL-5- and/or IL-13-high”) sputum cytokine profile. Unsupervised cluster analysis revealed 5 clusters. Patients with an “IL-4- and/or IL-13-high” pattern surprisingly did not cluster but were equally distributed among the 5 clusters. Patients with an “IL-5-, IL-17A-/F- and IL-25- high” profile were restricted to cluster 1 (n = 24) with increased sputum eosinophil as well as neutrophil counts and poor lung function parameters at baseline and 2 years later. Four other clusters were identified: “IL-5-high or IL-10-high” (n = 16), “IL-6-high” (n = 8), “IL-22-high” (n = 25). Cluster 5 (n = 132) consists of patients without “cytokine-high” pattern or patients with only high IL-4 and/or IL-13.ConclusionWe identified 5 unique asthma molecular phenotypes by biological clustering. Type 2 cytokines cluster with non-type 2 cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori type 2 versus non-type 2 molecular phenotypes. www.clinicaltrials.gov NCT01224938. Registered 18 October 2010.

【 授权许可】

CC BY   
© The Author(s). 2017