Imperial College London
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ProfessorIanAdcock

Faculty of Medicine, National Heart & Lung Institute

Professor of Respiratory Cell & Molecular Biology
 
 
 
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Contact

 

+44 (0)20 7594 7840ian.adcock Website

 
 
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Location

 

304Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mikus:2022:10.1183/13993003.00142-2021,
author = {Mikus, MS and Kolmert, J and Andersson, L and Ostling, J and Knowles, RG and Gomez, C and Ericsson, M and Thorngren, J-O and Khoonsari, PE and Dahlen, B and Kupczyk, M and De, Meulder B and Auffray, C and Bakke, PS and Beghe, B and Bel, EH and Caruso, M and Chanez, P and Chawes, B and Fowler, SJ and Gaga, M and Geiser, T and Gjomarkaj, M and Horvath, I and Howarth, PH and Johnston, SL and Joos, G and Krug, N and Montuschi, P and Musial, J and Nizankowska-Mogilnicka, E and Olsson, HK and Papi, A and Rabe, KF and Sandstrom, T and Shaw, DE and Siafakas, NM and Uhlen, M and Riley, JH and Bates, S and Middelveld, RJM and Wheelock, CE and Chung, KF and Adcock, IM and Sterk, PJ and Djukanovic, R and Nilsson, P and Dahlen, S-E and James, A},
doi = {10.1183/13993003.00142-2021},
journal = {European Respiratory Journal},
pages = {1--17},
title = {Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation},
url = {http://dx.doi.org/10.1183/13993003.00142-2021},
volume = {59},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Mikus,MS
AU  - Kolmert,J
AU  - Andersson,L
AU  - Ostling,J
AU  - Knowles,RG
AU  - Gomez,C
AU  - Ericsson,M
AU  - Thorngren,J-O
AU  - Khoonsari,PE
AU  - Dahlen,B
AU  - Kupczyk,M
AU  - De,Meulder B
AU  - Auffray,C
AU  - Bakke,PS
AU  - Beghe,B
AU  - Bel,EH
AU  - Caruso,M
AU  - Chanez,P
AU  - Chawes,B
AU  - Fowler,SJ
AU  - Gaga,M
AU  - Geiser,T
AU  - Gjomarkaj,M
AU  - Horvath,I
AU  - Howarth,PH
AU  - Johnston,SL
AU  - Joos,G
AU  - Krug,N
AU  - Montuschi,P
AU  - Musial,J
AU  - Nizankowska-Mogilnicka,E
AU  - Olsson,HK
AU  - Papi,A
AU  - Rabe,KF
AU  - Sandstrom,T
AU  - Shaw,DE
AU  - Siafakas,NM
AU  - Uhlen,M
AU  - Riley,JH
AU  - Bates,S
AU  - Middelveld,RJM
AU  - Wheelock,CE
AU  - Chung,KF
AU  - Adcock,IM
AU  - Sterk,PJ
AU  - Djukanovic,R
AU  - Nilsson,P
AU  - Dahlen,S-E
AU  - James,A
DO  - 10.1183/13993003.00142-2021
EP  - 17
PY  - 2022///
SN  - 0903-1936
SP  - 1
TI  - Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation
T2  - European Respiratory Journal
UR  - http://dx.doi.org/10.1183/13993003.00142-2021
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000798166900005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://erj.ersjournals.com/content/59/2/2100142
UR  - http://hdl.handle.net/10044/1/101722
VL  - 59
ER  -
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