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

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3100415 74 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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-2independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA. © 2022 European Respiratory Society. All rights reserved.
Έτος δημοσίευσης:
2022
Συγγραφείς:
Mikus, M.S.
Kolmert, J.
Andersson, L.I.
Östling, J.
Knowles, R.G.
Gómez, C.
Ericsson, M.
Thörngren, J.-O.
Khoonsari, P.E.
Dahlén, B.
Kupczyk, M.
de Meulder, B.
Auffray, C.
Bakke, P.S.
Beghe, B.
Bel, E.H.
Caruso, M.
Chanez, P.
Chawes, B.
Fowler, S.J.
Gaga, M.
Geiser, T.
Gjomarkaj, M.
Horváth, I.
Howarth, P.H.
Johnston, S.L.
Joos, G.
Krug, N.
Montuschi, P.
Musial, J.
Niżankowska-Mogilnicka, E.
Olsson, H.K.
Papi, A.
Rabe, K.F.
Sandström, T.
Shaw, D.E.
Siafakas, N.M.
Uhlén, M.
Riley, J.H.
Bates, S.
Middelveld, R.J.M.
Wheelock, C.E.
Chung, K.F.
Adcock, I.M.
Sterk, P.J.
Djukanovic, R.
Nilsson, P.
Dahlén, S.-E.
James, A.
Ahmed, H.
Balgoma, D.
Bansal, A.T.
Baribaud, F.
Bigler, J.
Billing, B.
Bisgaard, H.
Boedigheimer, M.J.
Bønnelykke, K.
Brandsma, J.
Brinkman, P.
Bucchioni, E.
Burg, D.
Bush, A.
Chaiboonchoe, A.
Checa, T.
Compton, C.H.
Corfield, J.
Cunoosamy, D.
D’Amico, A.
Emma, R.
Erpenbeck, V.J.
Erzen, D.
Fichtner, K.
Fitch, N.
Fleming, L.J.
Formaggio, E.
Frey, U.
Gahlemann, M.
Goss, V.
Guo, Y.-K.
Hashimoto, S.
Haughney, J.
Hedlin, G.
Hekking, P.-P.W.
Higenbottam, T.
Hohlfeld, J.M.
Holweg, C.T.J.
Knox, A.J.
Konradsen, J.
Lazarinis, N.
Lefaudeux, D.
Li, T.
Loza, M.J.
Lutter, R.
Manta, A.
Masefield, S.
Matthews, J.G.
Mazein, A.
Meiser, A.
Miralpeix, M.
Mores, N.
Murray, C.S.
Myles, D.
Naz, S.
Nordlund, B.
Pahus, L.
Pandis, I.
Pavlidis, S.
Postle, A.
Powel, P.
Rao, N.
Reinke, S.
Roberts, A.
Roberts, G.
Rowe, A.
Schofield, J.P.R.
Seibold, W.
Selby, A.
Sigmund, R.
Singer, F.
Sjödin, M.
Skipp, P.J.
Sousa, A.R.
Sun, K.
Thornton, B.
Uddin, M.
van Aalderen, W.M.
van Geest, M.
Vestbo, J.
Vissing, N.H.
Wagener, A.H.
Wagers, S.S.
Weiszhart, Z.
Wheelock, C.E.
Wheelock, Å.
Wilson, S.J.
Yasinska, V.
Brusselle, G.G.
Campbell, D.A.
Contoli, M.
Damm, K.
de Rudder, I.
Delin, I.
Devautour, C.
Duplaga, M.
Eduards, M.
Ek, A.
Ekström, T.
Figiel, E.
Gaber, F.
Gauw, S.
Gawlewicz-Mroczka, A.
Gerding, D.
Haque, S.
Hewitt, L.
Hiemstra, P.S.
Holgate, S.T.
Holloway, J.
Kania, A.
Kanniess, F.
Karlsson, Ö.
Kips, J.C.
Kumlin, M.
Lantz, A.-S.
Lazarinis, N.
Magnussen, H.
Mallia, P.
Martling, I.
Meziane, L.
Oikonomidou, E.
Olsson, M.
Pace, E.
Papadopouli, E.
Papadopoulos, N.
Plataki, M.
Profita, M.
Reinius, L.E.
Richter, K.
Robinson, D.S.
Romagnoli, M.
Samara, K.
Schelfhout, V.
Skedinger, M.
Stamataki, E.
ten Brinke, A.
Vachier, I.
Wallén-Nielsen, E.
van Veen, I.
Weersink, E.
Wilson, S.J.
Yasinska, V.
Zervas, E.
Ziolkowska-Graca, B.
U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcome) Study Group
BIOAIR (Longitudinal Assessment of Clinical Course
Biomarkers in Severe Chronic Airway Disease) Consortium
Περιοδικό:
European Respiratory Journal
Εκδότης:
European Respiratory Society
Τόμος:
59
Αριθμός / τεύχος:
2
Λέξεις-κλειδιά:
alpha 1 antichymotrypsin; apolipoprotein E; C reactive protein; carboxypeptidase; carboxypeptidase A3; complement component C9; complement factor I; glutathione transferase; interleukin 6; macrophage inflammatory protein; macrophage inflammatory protein 3; placebo; plasma protein; prednisolone; receptor activator of nuclear factor kappa B; sphingomyelin phosphodiesterase; sphingomyelin phosphodiesterase 3; transforming growth factor beta; unclassified drug, abnormally high substrate concentration in blood; adult; Article; asthma; body mass; chronic obstructive lung disease; cohort analysis; controlled study; disease association; disease severity; double blind procedure; extracellular matrix; female; human; human cell; inflammation; lipid metabolism; major clinical study; male; middle aged; neutrophil count; phenotype; protein blood level; protein targeting; quality of life; signal transduction; treatment duration; validation study
Επίσημο URL (Εκδότης):
DOI:
10.1183/13993003.00142-2021
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