title: The alternative complement pathway is dysregulated in patients with chronic heart failure.
abstract: The complement system, an important arm of the innate immune system, is activated in heart failure (HF). We hypothesized that HF patients are characterized by an imbalance of alternative amplification loop components; including properdin and complement factor D and the alternative pathway inhibitor factor H. These components and the activation product, terminal complement complex (TCC), were measured in plasma from 188 HF patients and 67 age- and sex- matched healthy controls by enzyme immunoassay. Our main findings were: (i) Compared to controls, patients with HF had significantly increased levels of factor D and TCC, and decreased levels of properdin, particularly patients with advanced clinical disorder (i.e., NYHA functional class IV), (ii) Levels of factor D and properdin in HF patients were correlated with measures of systemic inflammation (i.e., C-reactive protein), neurohormonal deterioration (i.e., Nt-proBNP), cardiac function, and deteriorated diastolic function, (iii) Low levels of factor H and properdin were associated with adverse outcome in univariate analysis and for factor H, this was also seen in an adjusted model. Our results indicate that dysregulation of circulating components of the alternative pathway explain the increased degree of complement activation and is related to disease severity in HF patients.
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Center for Heart Failure Research, University of Oslo, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
authors.forename: Negar
authors.initials: N
authors.lastname: Shahini
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Annika E
authors.initials: AE
authors.lastname: Michelsen
authors.affiliation: K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.|Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Linnaeus Centre for Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden.
authors.forename: Per H
authors.initials: PH
authors.lastname: Nilsson
authors.affiliation: K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
authors.forename: Karin
authors.initials: K
authors.lastname: Ekholt
authors.affiliation: Center for Heart Failure Research, University of Oslo, Oslo, Norway.|Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Kaspar
authors.initials: K
authors.lastname: Broch
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Christen P
authors.initials: CP
authors.lastname: Dahl
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.|Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Center for Heart Failure Research, University of Oslo, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.|Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Research Laboratory, Nordland Hospital, Bodø, and K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway.|Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Tom Eirik
authors.initials: TE
authors.lastname: Mollnes
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Center for Heart Failure Research, University of Oslo, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Center for Heart Failure Research, University of Oslo, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
authors.forename: Mieke C
authors.initials: MC
authors.lastname: Louwe
mesh_terms: D000368:Aged; D015415:Biomarkers; D016022:Case-Control Studies; D002908:Chronic Disease; D015897:Comorbidity; D017242:Complement Factor H / Q000276:immunology / Q000378:metabolism; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D006334:Heart Function Tests; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011414:Properdin / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011414:Properdin; D017242:Complement Factor H; D003165:Complement System Proteins