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dc.contributor.authorShahini, Negar
dc.contributor.authorUeland, Thor
dc.contributor.authorAuensen, Andreas
dc.contributor.authorMichelsen, Annika
dc.contributor.authorLudviksen, Judith K
dc.contributor.authorHussain, Amjad Iqbal
dc.contributor.authorPettersen, Kjell
dc.contributor.authorAakhus, Svend
dc.contributor.authorEspeland, Torvald
dc.contributor.authorLunde, Ida Gjervold
dc.contributor.authorKirschfink, Michael
dc.contributor.authorNilsson, Per
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorGullestad, Lars
dc.contributor.authorAukrust, Pål
dc.contributor.authorYndestad, Arne
dc.contributor.authorLouwe, Maria Cornelia
dc.date.accessioned2020-06-11T08:34:13Z
dc.date.available2020-06-11T08:34:13Z
dc.date.issued2019-09-24
dc.description.abstractInflammation is involved in initiation and progression of aortic stenosis (AS). However, the role of the complement system, a crucial component of innate immunity in AS, is unclear. We hypothesized that circulating levels of complement factor B (FB), an important component of the alternative pathway, are upregulated and could predict outcome in patients with severe symptomatic AS. Therefore, plasma levels of FB, Bb, and terminal complement complex were analyzed in three cohorts of patients with severe symptomatic AS and mild-to-moderate or severe asymptomatic AS (population 1, n = 123; population 2, n = 436; population 3, n = 61) and in healthy controls by enzyme immunoassays. Compared with controls, symptomatic AS patients had significantly elevated levels of FB (2.9- and 2.8-fold increase in population 1 and 2, respectively). FB levels in symptomatic and asymptomatic AS patients were comparable (population 2 and 3), and in asymptomatic patients FB correlated inversely with valve area. FB levels in population 1 and 2 correlated with terminal complement complex levels and measures of systemic inflammation (i.e., CRP), cardiac function (i.e., NT-proBNP), and cardiac necrosis (i.e., Troponin T). High FB levels were significantly associated with mortality also after adjusting for clinical and biochemical covariates (hazard ratio 1.37; p = 0.028, population 2). Plasma levels of the Bb fragment showed a similar pattern in relation to mortality. We concluded that elevated levels of FB and Bb are associated with adverse outcome in patients with symptomatic AS. Increased levels of FB in asymptomatic patients suggest the involvement of FB from the early phase of the disease.en_US
dc.identifier.citationShahini N, Ueland T, Auensen A, Michelsen A, Ludviksen JK, Hussain A, Pettersen K, Aakhus S, Espeland T, Lunde IG, Kirschfink M, Nilsson P, Mollnes TE, Gullestad L, Aukrust P, Yndestad A, Louwe MC. Increased complement factor B and Bb levels are associated with mortality in patients with severe aortic stenosis. Journal of Immunology. 2019;203(7):1973-1980en_US
dc.identifier.cristinIDFRIDAID 1738956
dc.identifier.doi10.4049/jimmunol.1801244
dc.identifier.issn0022-1767
dc.identifier.issn1550-6606
dc.identifier.urihttps://hdl.handle.net/10037/18519
dc.language.isoengen_US
dc.publisherAmerican Association of Immunologistsen_US
dc.relation.journalJournal of Immunology
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMEDBIO/240099/Norway/Metaflammation in cardiovascular disease//en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2019 The American Association of Immunologists, Inc.en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Communicable diseases: 776en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Infeksjonsmedisin: 776en_US
dc.titleIncreased complement factor B and Bb levels are associated with mortality in patients with severe aortic stenosisen_US
dc.type.versionacceptedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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