Frontiers in Immunology (Dec 2021)
The Alternative Complement Pathway Is Activated Without a Corresponding Terminal Pathway Activation in Patients With Heart Failure
- Margrethe Flesvig Holt,
- Margrethe Flesvig Holt,
- Annika E. Michelsen,
- Annika E. Michelsen,
- Negar Shahini,
- Elisabeth Bjørkelund,
- Christina Holt Bendz,
- Richard J. Massey,
- Richard J. Massey,
- Camilla Schjalm,
- Bente Halvorsen,
- Bente Halvorsen,
- Kaspar Broch,
- Kaspar Broch,
- Thor Ueland,
- Thor Ueland,
- Thor Ueland,
- Lars Gullestad,
- Lars Gullestad,
- Lars Gullestad,
- Per H. Nilsson,
- Per H. Nilsson,
- Pål Aukrust,
- Pål Aukrust,
- Pål Aukrust,
- Tom Eirik Mollnes,
- Tom Eirik Mollnes,
- Tom Eirik Mollnes,
- Tom Eirik Mollnes,
- Mieke C. Louwe
Affiliations
- Margrethe Flesvig Holt
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- Margrethe Flesvig Holt
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Annika E. Michelsen
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- Annika E. Michelsen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Negar Shahini
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- Elisabeth Bjørkelund
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Christina Holt Bendz
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Richard J. Massey
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Richard J. Massey
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Camilla Schjalm
- Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway
- Bente Halvorsen
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- Bente Halvorsen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Kaspar Broch
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Kaspar Broch
- K.G. Jebsen Cardiac Research Center, Center for Heart Failure Research, Faculty of Medicine, University of Oslo, Oslo, Norway
- Thor Ueland
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- Thor Ueland
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Thor Ueland
- Faculty of Health Sciences, K. G. Jebsen Thrombosis Research Center, University of Tromsø – The Arctic University of Norway, Tromsø, Norway
- Lars Gullestad
- Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Lars Gullestad
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Lars Gullestad
- K.G. Jebsen Cardiac Research Center, Center for Heart Failure Research, Faculty of Medicine, University of Oslo, Oslo, Norway
- Per H. Nilsson
- Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway
- Per H. Nilsson
- Linnaeus Centre for Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden
- Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- Pål Aukrust
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Pål Aukrust
- Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Tom Eirik Mollnes
- Department of Immunology, Oslo University Hospital Rikshospitalet and University of Oslo, Oslo, Norway
- Tom Eirik Mollnes
- Faculty of Health Sciences, K. G. Jebsen Thrombosis Research Center, University of Tromsø – The Arctic University of Norway, Tromsø, Norway
- Tom Eirik Mollnes
- Research Laboratory, Nordland Hospital, Bodø, Norway
- Tom Eirik Mollnes
- 0Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway
- Mieke C. Louwe
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
- DOI
- https://doi.org/10.3389/fimmu.2021.800978
- Journal volume & issue
-
Vol. 12
Abstract
ObjectiveDysregulation of the complement system has been described in patients with heart failure (HF). However, data on the alternative pathway are scarce and it is unknown if levels of factor B (FB) and the C3 convertase C3bBbP are elevated in these patients. We hypothesized that plasma levels of FB and C3bBbP would be associated with disease severity and survival in patients with HF.MethodsWe analyzed plasma levels of FB, C3bBbP, and terminal C5b-9 complement complex (TCC) in 343 HF patients and 27 healthy controls.ResultsCompared with controls, patients with HF had elevated levels of circulating FB (1.6-fold, p < 0.001) and C3bBbP (1.3-fold, p < 0.001). In contrast, TCC, reflecting the terminal pathway, was not significantly increased (p = 0.15 vs controls). FB was associated with NT-proBNP, troponin, eGFR, and i.e., C-reactive protein. FB, C3bBbP and TCC were not associated with mortality in HF during a mean follow up of 4.3 years.ConclusionOur findings suggest that in patients with HF, the alternative pathway is activated. However, this is not accompanied by activation of the terminal pathway.
Keywords