Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation - Aix-Marseille Université Access content directly
Journal Articles European Respiratory Journal Year : 2022

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

Maria Sparreman Mikus
  • Function : Author
Johan Kolmert
Lars Andersson
  • Function : Author
Jörgen Östling
  • Function : Author
Richard Knowles
  • Function : Author
Cristina Gómez
Magnus Ericsson
  • Function : Author
John-Olof Thörngren
  • Function : Author
Payam Emami Khoonsari
  • Function : Author
Barbro Dahlén
  • Function : Author
Maciej Kupczyk
  • Function : Author
Bertrand de Meulder
Charles Auffray
  • Function : Author
Per Bakke
  • Function : Author
Bianca Beghe
  • Function : Author
Elisabeth Bel
  • Function : Author
Massimo Caruso
Bo Chawes
  • Function : Author
Stephen Fowler
Mina Gaga
Thomas Geiser
  • Function : Author
Mark Gjomarkaj
  • Function : Author
Ildikó Horváth
  • Function : Author
Peter Howarth
Sebastian Johnston
  • Function : Author
Guy Joos
Norbert Krug
  • Function : Author
Paolo Montuschi
  • Function : Author
Jacek Musial
  • Function : Author
Ewa Niżankowska-Mogilnicka
  • Function : Author
Henric Olsson
  • Function : Author
Alberto Papi
Klaus Rabe
  • Function : Author
Thomas Sandström
  • Function : Author
Dominick Shaw
Nikolaos Siafakas
  • Function : Author
Mathias Uhlén
  • Function : Author
John Riley
  • Function : Author
Stewart Bates
  • Function : Author
Roelinde J.M. Middelveld
  • Function : Author
Craig Wheelock
Kian Fan Chung
  • Function : Author
Ian Adcock
Peter Sterk
  • Function : Author
Ratko Djukanovic
  • Function : Author
Peter Nilsson
Sven-Erik Dahlén
Anna James
  • Function : Author

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.

Dates and versions

hal-03654460 , version 1 (28-04-2022)

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Maria Sparreman Mikus, Johan Kolmert, Lars Andersson, Jörgen Östling, Richard Knowles, et al.. Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation. European Respiratory Journal, 2022, 59 (2), pp.2100142. ⟨10.1183/13993003.00142-2021⟩. ⟨hal-03654460⟩
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