Sparreman Mikus, MariaMariaSparreman MikusKolmert, JohanJohanKolmertAndersson, Lars ILars IAnderssonÖstling, JörgenJörgenÖstlingKnowles, Richard GRichard GKnowlesGómez, CristinaCristinaGómezEricsson, MagnusMagnusEricssonThörngren, John-OlofJohn-OlofThörngrenEmami Khoonsari, PayamPayamEmami KhoonsariDahlén, BarbroBarbroDahlénKupczyk, MaciejMaciejKupczykDe Meulder, BertrandBertrandDe MeulderAuffray, CharlesCharlesAuffrayBakke, Per SPer SBakkeBeghe, BiancaBiancaBegheBel, Elisabeth HElisabeth HBelCaruso, MassimoMassimoCarusoChanez, PascalPascalChanezChawes, BoBoChawesFowler, Stephen JStephen JFowlerGaga, MinaMinaGagaGeiser, ThomasThomasGeiserGjomarkaj, MarkMarkGjomarkajHorváth, IldikóIldikóHorváthHowarth, Peter HPeter HHowarthJohnston, Sebastian LSebastian LJohnstonJoos, GuyGuyJoosKrug, NorbertNorbertKrugMontuschi, PaoloPaoloMontuschiMusial, JacekJacekMusialNiżankowska-Mogilnicka, EwaEwaNiżankowska-MogilnickaOlsson, Henric KHenric KOlssonPapi, AlbertoAlbertoPapiRabe, Klaus FKlaus FRabeSandström, ThomasThomasSandströmShaw, Dominick EDominick EShawSiafakas, Nikolaos MNikolaos MSiafakasUhlén, MathiasMathiasUhlénRiley, John HJohn HRileyBates, StewartStewartBatesMiddelveld, Roelinde J MRoelinde J MMiddelveldWheelock, Craig ECraig EWheelockChung, Kian FanKian FanChungAdcock, Ian MIan MAdcockSterk, Peter JPeter JSterkDjukanovic, RatkoRatkoDjukanovicNilsson, PeterPeterNilssonDahlén, Sven-ErikSven-ErikDahlénJames, AnnaAnnaJames2024-10-092024-10-092022-02https://boris-portal.unibe.ch/handle/20.500.12422/67973RATIONALE 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.en600 - Technology::610 - Medicine & healtharticle10.48350/1662523473722010.1183/13993003.00142-2021