Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation
-
Published:2021-11-04
Issue:
Volume:
Page:2100142
-
ISSN:0903-1936
-
Container-title:European Respiratory Journal
-
language:en
-
Short-container-title:Eur Respir J
Author:
Mikus Maria Sparreman, Kolmert Johan, Andersson Lars I., Östling Jörgen, Knowles Richard G., Gómez CristinaORCID, Ericsson Magnus, Thörngren John-Olof, Khoonsari Payam Emami, Dahlén Barbro, Kupczyk Maciej, De Meulder Bertrand, Auffray Charles, Bakke Per S., Beghe Bianca, Bel Elisabeth H., Caruso MassimoORCID, Chanez Pascal, Chawes Bo, Fowler Stephen J.ORCID, Gaga MinaORCID, Geiser Thomas, Gjomarkaj Mark, Horváth Ildikó, Howarth Peter H., Johnston Sebastian L., Joos GuyORCID, Krug Norbert, Montuschi Paolo, Musial Jacek, Niżankowska-Mogilnicka Ewa, Olsson Henric K., Papi Alberto, Rabe Klaus F., Sandström Thomas, Shaw Dominick E.ORCID, Siafakas Nikolaos M., Uhlen Mathias, Riley John H., Bates Stewart, Middelveld Roelinde J.M., Wheelock Craig E.ORCID, Chung Kian Fan, Adcock Ian M.ORCID, Sterk Peter J., Djukanovic Ratko, Nilsson PeterORCID, Dahlén Sven-Erik, James Anna, ,
Abstract
RationaleAsthma phenotyping requires novel biomarker discovery.ObjectivesTo identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, chronic obstructive pulmonary disease (COPD) subjects and healthy controls (HC).MethodsAn antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HC in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a two-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED.ResultsIn U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HC. Ten proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, RANK, TGF-β1, and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, hsCRP, and BMI, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation.ConclusionsThe plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers, and validated several proteins with established involvement in the pathophysiology of severe asthma.
Publisher
European Respiratory Society (ERS)
Subject
Pulmonary and Respiratory Medicine
Cited by
20 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|