Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation.

Sparreman Mikus, Maria; Kolmert, Johan; Andersson, Lars I; Östling, Jörgen; Knowles, Richard G; Gómez, Cristina; Ericsson, Magnus; Thörngren, John-Olof; Emami Khoonsari, Payam; 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; ... (2022). Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation. The European respiratory journal, 59(2) European Respiratory Society 10.1183/13993003.00142-2021

Preview

Text Geiser_Plasma_proteins.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial (CC-BY-NC). Download (1MB) | Preview

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.

Interest & Impact

Downloads

216 since deposited on 09 Mar 2022
40 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item