• Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis 

      Hellerud, Bernt C; Orrem, Hilde L.; Dybwik, Knut Gustav; Pischke, Søren Erik; Barratt-Due, Andreas; Castellheim, Albert; Fure, Hilde; Bergseth, Grete; Christiansen, Dorte; Nunn, Miles A.; Espevik, Terje; Lau, Corinna; Brandtzæg, Petter; Nielsen, Erik Waage; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-02-27)
      Background<br> Fulminant meningococcal sepsis, characterized by overwhelming innate immune activation, mostly affects young people and causes high mortality. This study aimed to investigate the effect of targeting two key molecules of innate immunity, complement component C5, and co-receptor CD14 in the Toll-like receptor system, on the inflammatory response in meningococcal sepsis.<p> Methods ...
    • Complement activation is a crucial pathogenic factor in catastrophic antiphospholipid syndrome. 

      Barratt-Due, Andreas; Fløisand, Yngvar; Lang, Hilde Elisabeth; Kvam, Ann Kristin; Holme, Pål Andre; Bergseth, Grete; Tjønnfjord, Geir Erland; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-04-22)
      Catastrophic antiphospholipid syndrome is associated with excessive complement activation explaining the clinical efficacy of complement inhibitory treatment.
    • Complement component 5 does not interfere with physiological hemostasis but is essential for Escherichia coli-induced coagulation accompanied by Toll-like receptor 4 

      Landsem, Anne; Fure, Hilde; Ludviksen, Judith K; Christiansen, Dorte; Lau, Corinna; Mathisen, Monica Dammen; Bergseth, Grete; Nymo, Stig Haugset; Lappegård, Knut Tore; Woodruff, T. M.; Espevik, Terje; Mollnes, Tom Eirik; Brekke, Ole-Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-12-19)
      There is a close cross‐talk between complement, Toll‐like receptors (TLRs) and coagulation. The role of the central complement component 5 (C5) in physiological and pathophysiological hemostasis has not, however, been fully elucidated. This study examined the effects of C5 in normal hemostasis and in <i>Escherichia coli</i>‐induced coagulation and tissue factor (TF) up‐regulation. Fresh whole blood ...
    • A conformational change of complement C5 is required for thrombin-mediated cleavage, revealed by a novel ex vivo human whole blood model preserving full thrombin activity 

      Nilsson, Per; Johnson, Christina; Quach, Huy Quang; Macpherson, Alex; Durrant, Oliver; Pischke, Soeren; Fure, Hilde; Landsem, Anne; Bergseth, Grete; Schjalm, Camilla; Haugaard-Kedström, Linda M.; Huber-Lang, Markus; van den Elsen, Jean; Brekke, Ole-Lars; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-09-15)
      Thrombin activation of C5 connects thrombosis to inflammation. Complement research in whole blood ex vivo necessitates anticoagulation, which potentially interferes with the inflammatory modulation by thrombin. We challenged the concept of thrombin as an activator of native C5 by analyzing complement activation and C5 cleavage in human whole blood anticoagulated with Gly-Pro-Arg-Pro (GPRP), a peptide ...
    • Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn 

      Hallstensen, Randi; Bergseth, Grete; Foss, Stian; Jæger, Steinar; Gedde-Dahl, Thobias; Holt, jan; Christiansen, Dorte; Lau, Corinna; Brekke, Ole Lars; Armstrong, Elina; Stefanovic, Vedran; Andersen, Jan Terje; Sandlie, Inger; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-11-13)
      Eculizumab is a humanized IgG2/4 chimeric anti-complement C5 antibody used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) or atypical hemolytic uremic syndrome. The aim of this study was to evaluate whether or not the complement activity in newborns from pregnant women who receive eculizumab is impaired. A novel eculizumab-C5 complex (E-C5) specific assay was developed and ...
    • Eculizumab-C5 complexes express a C5a neoepitope in vivo: Consequences for interpretation of patient complement analyses 

      Nilsson, Per; Thomas, Anub Mathew; Bergseth, Grete; Gustavsen, Alice; Volokhina, Elena B.; van den Heuvel, Lambertus P.; Barratt-Due, Andreas; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-06-10)
      The complement system has obtained renewed clinical focus due to increasing number of patients treated with eculizumab, a monoclonal antibody inhibiting cleavage of C5 into C5a and C5b. The FDA approved indications are paroxysmal nocturnal haemoglobinuria and atypical haemolytic uremic syndrome, but many other diseases are candidates for complement inhibition. It has been postulated that eculizumab ...
    • Effect of the anticoagulant, storage time and temperature of blood samples on the concentrations of 27 multiplex assayed cytokines – Consequences for defining reference values in healthy humans 

      Hennø, Linda Torrissen; Storjord, Elin; Christiansen, Dorte; Bergseth, Grete; Ludviksen, Judith K; Fure, Hilde; Barene, Svein; Nielsen, Erik Waage; Mollnes, Tom Eirik; Brekke, Ole Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-06-06)
      Cytokines are potentially useful biomarkers of sepsis and other inflammatory conditions. Many cytokines can be released by leukocytes and platelets after sampling. The sampling and processing techniques are consequently critically important to measure the <i>in vivo</i> levels. We therefore examined the effects of four different anticoagulants, EDTA, citrate, lepirudin, heparin compared to serum, ...
    • Effect on mother and child of eculizumab given before caesarean section in a patient with severe antiphospholipid syndrome 

      Gustavsen, Alice; Skattum, Lillemor; Bergseth, Grete; Lorentzen, Bjørg; Fløisand, Yngvar; Bosnes, Vidar; Mollnes, Tom Eirik; Barratt-Due, Andreas (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-03-01)
      Rationale:Antiphospholipid syndrome (APS) in pregnancy may trigger the lifethreatening catastrophic antiphospholipid syndrome (CAPS). Complement activation is implicated in the pathogenesis, and inhibition of complement factor C5 is suggested as an additional treatment option.<p> Patient concerns, diagnosis and interventions: We present a pregnant patient treated with the C5-inhibitor eculizumab ...
    • Granulocyte and monocyte CD11b expression during plasma separation is dependent on complement factor 5 (C5) – an ex vivo study with blood from a C5-deficient individual 

      Hardersen, Randolf Inge; Enebakk, Terje; Christiansen, Dorte; Bergseth, Grete; Brekke, Ole-Lars; Mollnes, Tom Eirik; Lappegård, Knut Tore; Hovland, Anders (Journal article; Tidsskriftartikkel, 2018)
      The aim of the study was to investigate the role of complement factor 5 (C5) in reactions elicited by plasma separation using blood from a C5‐deficient (C5D) individual, comparing it to C5‐deficient blood reconstituted with C5 (C5DR) and blood from healthy donors. Blood was circulated through an <i>ex vivo</i> plasma separation model. Leukocyte CD11b expression and leukocyte–platelet conjugates were ...