Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation
Mikus, Maria Sparreman; Kolmert, Johan; Andersson, Lars I.; Östling, Jörgen; Knowles, Richard G.; Gómez, Cristina; 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, Massimo; Chanez, Pascal; Chawes, Bo; Fowler, Stephen J.; Gaga, Mina; Geiser, Thomas; Gjomarkaj, Mark; Horváth, Ildikó; Howarth, Peter H.; Johnston, Sebastian L.; Joos, Guy; Krug, Norbert; Montuschi, Paolo; Musial, Jacek; Niżankowska-Mogilnicka, Ewa; Olsson, Henric K.; Papi, Alberto; Rabe, Klaus F.; Sandström, Thomas; Shaw, Dominick E.; Siafakas, Nikolaos M.; Uhlén, Mathias; Riley, John H.; Bates, Stewart; Middelveld, Roelinde J.M.; Wheelock, Craig E.; Chung, Kian Fan; Adcock, Ian M.; Sterk, Peter J.; Djukanovic, Ratko; Nilsson, Peter; Dahlén, Sven-Erik; James, Anna
Journal article, Peer reviewed
Published version
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https://hdl.handle.net/11250/3025166Utgivelsesdato
2022Metadata
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- Department of Clinical Science [2294]
- Registrations from Cristin [9489]
Sammendrag
Rationale Asthma phenotyping requires novel biomarker discovery.
Objectives To 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, COPD subjects and healthy controls (HCs).
Methods An 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 HCs 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 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED.
Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 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, TNF receptor superfamily member 11a, transforming growth factor-β 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, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation.
Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.