Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation
Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation
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.
Sparreman Mikus, Maria
4011e89d-9bbe-4f26-a4ad-668d21708470
Kolmert, Johan
031a7e44-0f44-45b0-a2ed-0d095d20f449
Andersson, Lars I
03b0017e-9b60-4a0a-ad58-0902b51e4fca
Östling, Jörgen
98f5fad2-945e-4061-8791-3c89946fb821
Knowles, Richard G
a0884b16-f993-4579-b49c-502a986d62ad
Gómez, Cristina
d1751750-3b59-4f7d-9911-4f857a597788
Ericsson, Magnus
4ef5d9a1-5e77-44ca-9725-1b0f2c6202a5
Thörngren, John-Olof
5282f34c-99d3-47d1-8bae-8f5c210eeb94
Emami Khoonsari, Payam
89a3ee0c-2406-4744-a3d3-dd15345304f9
Dahlén, Barbro
9a1ebc34-9a8e-46a3-9933-fda2cbdd4ab9
Kupczyk, Maciej
ed0ca49c-5b08-4427-8c4b-a34a0d495c60
De Meulder, Bertrand
2eb16e68-bc1a-4e71-bc76-a6ebcb079cbd
Auffray, Charles
16fdf8f6-e7bc-4559-b6b6-d425160867c6
Bakke, Per S
14e4943c-16b0-4f9f-ab31-a72c6f02b581
Beghe, Bianca
69dfbff6-7d03-4cdf-a53a-32c805ffac59
Bel, Elisabeth H
a4116590-ade0-4af1-9374-3147a8896a2a
Caruso, Massimo
d6a59da8-4f93-4926-93a6-e7c3b90b480f
Chanez, Pascal
695ba8e7-e6b7-49db-a88f-e5f5a366b869
Chawes, Bo
ef75fcd9-762f-4900-983f-f6eb68b2f063
Fowler, Stephen J
7a077c2e-22e7-4a0c-b781-eec92fb931c8
Gaga, Mina
c7eae7fb-6632-4bdb-af14-f6b61ec6bb66
Geiser, Thomas
180f764c-bc92-4f82-b281-702d48dfa7e8
Gjomarkaj, Mark
1a6b364f-7b99-41ef-9e23-94f2bfa8ddde
Horváth, Ildikó
58e508ba-1b62-4ea5-a656-dda9498f90c7
Howarth, Peter H
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Johnston, Sebastian L
90e0ef79-cfde-40e0-b301-90d3063ee036
Joos, Guy
ba4411a8-014a-4b1c-b4e9-7bb0f5d6f90d
Krug, Norbert
68944b71-ec40-4d74-9f8f-773ea8599b0a
Montuschi, Paolo
10568e50-5a5f-47b3-9ac8-6a630c30882c
Musial, Jacek
4cc2db1c-776b-4f5a-8ec9-f8362ef9a6b9
Niżankowska-Mogilnicka, Ewa
3478af7c-6454-420a-8021-cc6590fc29ea
Olsson, Henric K
354ef3d9-f981-4ff5-a7c8-51fd323442cf
Papi, Alberto
8447eef8-34fd-482e-8e91-f8231acd05f7
Rabe, Klaus F
918f415f-3b37-4539-b4ba-30d989e866a8
Sandström, Thomas
77a4c11d-a84f-4a52-9bfe-4ec83f62363a
Shaw, Dominick E
83e98e0a-fd2d-4c44-9249-6ac3ebd9614f
Siafakas, Nikolaos M
7659bd33-b5a1-479d-bd7c-5df60be40642
Uhlén, Mathias
7e3d7ac5-27eb-40d2-b07c-d9787e48d252
Riley, John H
66454d3a-c673-4b84-b66b-40fab791d61d
Bates, Stewart
1be75e2f-b076-459a-a55b-9377ce2aa0e3
Middelveld, Roelinde J M
04517658-8195-44c8-ac93-29cafc650d5d
Wheelock, Craig E
a22e130a-c8b7-4fdf-ad52-fc39635063bc
Chung, Kian Fan
dc062fa0-b6c4-4b03-a0c2-917904e0ea2a
Adcock, Ian M
427153bc-3b8b-4066-aa4e-5bc41a6c36dd
Sterk, Peter J
cffc8681-7dc8-4328-ac93-4d5d5c4319b9
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Nilsson, Peter
e615060f-f672-4f3a-ba91-b3599a4dbec5
Dahlén, Sven-Erik
9e18ae23-c6a1-413c-93fe-203949a4dcda
James, Anna
6257742c-ce51-46b7-ad39-4f141bf77fe2
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
Sparreman Mikus, Maria
4011e89d-9bbe-4f26-a4ad-668d21708470
Kolmert, Johan
031a7e44-0f44-45b0-a2ed-0d095d20f449
Andersson, Lars I
03b0017e-9b60-4a0a-ad58-0902b51e4fca
Östling, Jörgen
98f5fad2-945e-4061-8791-3c89946fb821
Knowles, Richard G
a0884b16-f993-4579-b49c-502a986d62ad
Gómez, Cristina
d1751750-3b59-4f7d-9911-4f857a597788
Ericsson, Magnus
4ef5d9a1-5e77-44ca-9725-1b0f2c6202a5
Thörngren, John-Olof
5282f34c-99d3-47d1-8bae-8f5c210eeb94
Emami Khoonsari, Payam
89a3ee0c-2406-4744-a3d3-dd15345304f9
Dahlén, Barbro
9a1ebc34-9a8e-46a3-9933-fda2cbdd4ab9
Kupczyk, Maciej
ed0ca49c-5b08-4427-8c4b-a34a0d495c60
De Meulder, Bertrand
2eb16e68-bc1a-4e71-bc76-a6ebcb079cbd
Auffray, Charles
16fdf8f6-e7bc-4559-b6b6-d425160867c6
Bakke, Per S
14e4943c-16b0-4f9f-ab31-a72c6f02b581
Beghe, Bianca
69dfbff6-7d03-4cdf-a53a-32c805ffac59
Bel, Elisabeth H
a4116590-ade0-4af1-9374-3147a8896a2a
Caruso, Massimo
d6a59da8-4f93-4926-93a6-e7c3b90b480f
Chanez, Pascal
695ba8e7-e6b7-49db-a88f-e5f5a366b869
Chawes, Bo
ef75fcd9-762f-4900-983f-f6eb68b2f063
Fowler, Stephen J
7a077c2e-22e7-4a0c-b781-eec92fb931c8
Gaga, Mina
c7eae7fb-6632-4bdb-af14-f6b61ec6bb66
Geiser, Thomas
180f764c-bc92-4f82-b281-702d48dfa7e8
Gjomarkaj, Mark
1a6b364f-7b99-41ef-9e23-94f2bfa8ddde
Horváth, Ildikó
58e508ba-1b62-4ea5-a656-dda9498f90c7
Howarth, Peter H
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Johnston, Sebastian L
90e0ef79-cfde-40e0-b301-90d3063ee036
Joos, Guy
ba4411a8-014a-4b1c-b4e9-7bb0f5d6f90d
Krug, Norbert
68944b71-ec40-4d74-9f8f-773ea8599b0a
Montuschi, Paolo
10568e50-5a5f-47b3-9ac8-6a630c30882c
Musial, Jacek
4cc2db1c-776b-4f5a-8ec9-f8362ef9a6b9
Niżankowska-Mogilnicka, Ewa
3478af7c-6454-420a-8021-cc6590fc29ea
Olsson, Henric K
354ef3d9-f981-4ff5-a7c8-51fd323442cf
Papi, Alberto
8447eef8-34fd-482e-8e91-f8231acd05f7
Rabe, Klaus F
918f415f-3b37-4539-b4ba-30d989e866a8
Sandström, Thomas
77a4c11d-a84f-4a52-9bfe-4ec83f62363a
Shaw, Dominick E
83e98e0a-fd2d-4c44-9249-6ac3ebd9614f
Siafakas, Nikolaos M
7659bd33-b5a1-479d-bd7c-5df60be40642
Uhlén, Mathias
7e3d7ac5-27eb-40d2-b07c-d9787e48d252
Riley, John H
66454d3a-c673-4b84-b66b-40fab791d61d
Bates, Stewart
1be75e2f-b076-459a-a55b-9377ce2aa0e3
Middelveld, Roelinde J M
04517658-8195-44c8-ac93-29cafc650d5d
Wheelock, Craig E
a22e130a-c8b7-4fdf-ad52-fc39635063bc
Chung, Kian Fan
dc062fa0-b6c4-4b03-a0c2-917904e0ea2a
Adcock, Ian M
427153bc-3b8b-4066-aa4e-5bc41a6c36dd
Sterk, Peter J
cffc8681-7dc8-4328-ac93-4d5d5c4319b9
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Nilsson, Peter
e615060f-f672-4f3a-ba91-b3599a4dbec5
Dahlén, Sven-Erik
9e18ae23-c6a1-413c-93fe-203949a4dcda
James, Anna
6257742c-ce51-46b7-ad39-4f141bf77fe2