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

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

Mikus, MS (författare): Karolinska Institutet,Dept of Protein Science, KTH Royal Institute of Technology, SciLifeLab, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden,Dept of Thoracic Medicine, Medical School, University of Crete, Heraklion, Crete, Greece

Kolmert, J (författare): Karolinska Institutet,Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden

Andersson, LI (författare): Karolinska Institutet,Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden

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Ostling, J (författare): Gothenburg, Sweden

Knowles, RG (författare): Knowles Consulting, Stevenage Bioscience Catalyst, Stevenage, United Kingdom

Gomez, C (författare): Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden

Ericsson, M (författare): Dept of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden

Thorngren, JO (författare): Dept of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden

Khoonsari, PE (författare): Dept of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Solna, Sweden

Dahlen, B (författare): Karolinska Institutet,Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Dept of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden

Kupczyk, M (författare): Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Dept of Internal Medicine, Asthma and Allergy, Medical University of Lodz, University of Lodz, Lodz, Poland

De Meulder, B (författare): European Institute for Systems Biology and Medicine, Lyon, France,Dept of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

Auffray, C (författare): European Institute for Systems Biology and Medicine, Lyon, France

Bakke, PS (författare): Dept of Clinical Science, University of Bergen, Bergen, Norway

Beghe, B (författare)

Bel, EH (författare): Dept of Respiratory Medicine, University of Amsterdam, Amsterdam, Netherlands

Caruso, M (författare): Dept of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy

Chanez, P (författare): Assistance Publique des Hôpitaux de Marseille, Clinique des Bronches, Allergies et Sommeil, Aix Marseille Université, Marseille, France

Chawes, B (författare): COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

Fowler, SJ (författare): Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester; Manchester Academic Health Science Centre and NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, UK

Gaga, M (författare): Respiratory Medicine Dept and Asthma Centre, Athens Chest Hospital "Sotiria", University of Athens, Athens, Greece

Geiser, T (författare): Dept for Pulmonary Medicine, University Hospital and University of Bern, Bern, Switzerland

Gjomarkaj, M (författare): Institute for Research and Biomedical Innovation, Italian National Research Council, Palermo, Italy

Horvath, I (författare): Dept of Pulmonology, Semmelweis University, Budapest, Hungary

Howarth, PH (författare): NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom

Johnston, SL (författare): National Heart and Lung Institute, Imperial College London, London, United Kingdom

Joos, G (författare): Dept of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium

Krug, N (författare): Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany

Montuschi, P (författare): Dept of Pharmacology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy

Musial, J (författare): Karolinska Institutet

Nizankowska-Mogilnicka, E (författare): Dept of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland

Olsson, HK (författare): Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Papi, A (författare): Division of lnternal and Cardiorespiratory Medicine, University of Ferrara, Ferrara, Italy

Rabe, KF (författare): Dept of Internal Medicine, Christian Albrechts University Kiel, Kiel, Germany

Sandström, Thomas, 1957- (författare): Umeå universitet,Avdelningen för medicin

Shaw, DE (författare): Karolinska Institutet

Siafakas, NM (författare)

Uhlén, Mathias (författare): KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Karolinska Inst, Dept Neurosci, Stockholm, Sweden.

Riley, JH (författare): Respiratory Therapeutic Unit, GlaxoSmithKline, London, United Kingdom

Bates, S (författare): Respiratory Therapeutic Unit, GlaxoSmithKline, London, United Kingdom

Middelveld, RJM (författare): Karolinska Institutet

Wheelock, CE (författare): Karolinska Institutet,Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Dept of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Dept of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden

Chung, KF (författare): National Heart and Lung Institute, Imperial College London, London, United Kingdom

Adcock, IM (författare): National Heart and Lung Institute, Imperial College London, London, United Kingdom

Sterk, PJ (författare): Dept of Respiratory Medicine, University of Amsterdam, Amsterdam, Netherlands

Djukanovic, R (författare): NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom

Nilsson, Peter (författare): KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik

Dahlen, SE (författare): Karolinska Institutet,Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Dept of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden

James, A (författare): Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden,Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Karolinska Inst, Ctr Allergy Res, Stockholm, Sweden.

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(creator_code:org_t)

2021-11-04
2022
Engelska.
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 59:2

Relaterad länk:: https://erj.ersjourn...; visa fler...; https://doi.org/10.1...; https://umu.diva-por... (primary) (Raw object); http://kipublication...; https://doi.org/10.1...; https://urn.kb.se/re...; https://urn.kb.se/re...; visa färre...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

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Asthma phenotyping requires novel biomarker discovery.ObjectivesTo 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).MethodsAn 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.ResultsIn 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.ConclusionsThe 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.

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

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