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

Abstract

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.

• Authors: Maria Sparreman Mikus, Johan Kolmert, Lars I Andersson, Jörgen Östling, Richard G Knowles, Cristina Gómez, Magnus Ericsson, John-Olof Thörngren, Payam Emami Khoonsari, Barbro Dahlén, Maciej Kupczyk, Bertrand De Meulder, Charles Auffray, Per S Bakke, Bianca Beghe, Elisabeth H Bel, Massimo Caruso, Pascal Chanez, Bo Chawes, Stephen J Fowler, Mina Gaga, Thomas Geiser, Mark Gjomarkaj, Ildikó Horváth, Peter H Howarth, Sebastian L Johnston, Guy Joos, Norbert Krug, Paolo Montuschi, Jacek Musial, Ewa Niżankowska-Mogilnicka, Henric K Olsson, Alberto Papi, Klaus F Rabe, Thomas Sandström, Dominick E Shaw, Nikolaos M Siafakas, Mathias Uhlén, John H Riley, Stewart Bates, Roelinde J M Middelveld, Craig E Wheelock, Kian Fan Chung, Ian M Adcock, Peter J Sterk, Ratko Djukanovic, Peter Nilsson, Sven-Erik Dahlén, Anna James, U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcome) Study Group and the BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) Consortium
• Journal: The European respiratory journal (Eur Respir J) Vol. 59 Issue 2 (02 2022) ISSN: 1399-3003 [Electronic] England
• PMID: 34737220 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright ©The authors 2022.

Chemical References

• Blood Proteins
• Steroids

Topics

• Asthma
• Blood Proteins
• Humans
• Inflammation (metabolism)
• Proteomics
• Quality of Life
• Severity of Illness Index
• Steroids (therapeutic use)