• The Alternative Complement Pathway Is Activated Without a Corresponding Terminal Pathway Activation in Patients With Heart Failure 

      Shahini, Negar; Bjørkelund, Elisabeth; Bendz, Christina; Massey, Richard J; Schjalm, Camilla; Halvorsen, Bente; Broch, Kaspar; Ueland, Thor; Gullestad, Lars; Nilsson, Per H.; Aukrust, Pål; Mollnes, Tom Eirik; Louwe, Maria Cornelia; Holt, Margrethe Flesvig; Michelsen, Annika E. (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-24)
      Objective: Dysregulation 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 ...
    • Combined Inhibition of C5 and CD14 Attenuates Systemic Inflammation in a Piglet Model of Meconium Aspiration Syndrome 

      Thomas, Anub Mathew; Schjalm, Camilla; Nilsson, Per; Lindenskov, Paal Helge H.; Rørtveit, Runa; Solberg, Rønnaug; Saugstad, Ola Didrik; Berglund, Magnus M.; Strömberg, Patrik; Lau, Corinna; Espevik, Terje; Jansen, Johan Høgset; Castellheim, Albert; Mollnes, Tom Eirik; Barratt-Due, Andreas (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-02-27)
      <p><i>Background</i>: Meconium aspiration syndrome (MAS) is a severe lung condition affecting newborns and it can lead to a systemic inflammatory response. We previously documented complement activation and cytokine release in a piglet MAS model. Additionally, we showed ex vivo that meconium-induced inflammation was dependent on complement and Toll-like receptors.</p> <p><i>Objectives</i>: To ...
    • Complement Activation in 22q11.2 Deletion Syndrome 

      Grinde, Dina; Aresvik, Dina Mikhailovna; Øverland, Torstein; Lima, Kari; Schjalm, Camilla; Mollnes, Tom Eirik; Abrahamsen, Tore G (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-03-09)
      The 22q11.2 deletion syndrome (22q11.2 del), also known as DiGeorge syndrome, is a genetic disorder with an estimated incidence of 1:3000 to 1:6000 births. These patients may suffer from affection of many organ systems with cardiac malformations, immunodeficiency, hypoparathyroidism, autoimmunity, palate anomalies, and psychiatric disorders being the most frequent. The importance of the complement ...
    • Complement activation is associated with poor outcome after out-of-hospital cardiac arrest 

      Chaban, Viktoriia; Nakstad, Espen R.; Stær-Jensen, Henrik; Schjalm, Camilla; Seljeflot, Ingebjørg; Vaage, Ingvar Jarle; Lundqvist, Christofer; Saltyte Benth, Jurate; Sunde, Kjetil; Mollnes, Tom Eirik; Andersen, Geir Øystein; Pischke, Soeren (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-06-11)
      Background - Cardiopulmonary resuscitation after cardiac arrest initiates a whole-body ischemia-reperfusion injury, which may activate the innate immune system, including the complement system. We hypothesized that complement activation and subsequent release of soluble endothelial activation markers were associated with cerebral outcome including death.<p> <p>Methods - Outcome was assessed at ...
    • 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 ...
    • Ficolins do not alter host immune responses to lipopolysaccharide-induced inflammation in vivo 

      Genster, Ninette; Østrup, Olga; Schjalm, Camilla; Mollnes, Tom Eirik; Cowland, Jack B.; Garred, Peter (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-06-20)
      Ficolins are a family of pattern recognition molecules that are capable of activating the lectin pathway of complement. A limited number of reports have demonstrated a protective role of ficolins in animal models of infection. In addition, an immune modulatory role of ficolins has been suggested. Yet, the contribution of ficolins to inflammatory disease processes remains elusive. To address this, ...
    • Increased interleukin-6 and macrophage chemoattractant protein-1 are associated with respiratory failure in COVID-19 

      Jørgensen, Marthe Jøntvedt; Holter, Jan Cato; Christensen, Erik; Schjalm, Camilla; Tonby, Kristian; Pischke, Soeren; Jenum, Synne; Skeie, Linda Gail; Nur, Sarah; Lind, Andreas; Opsand, Hanne; Enersen, Tone Burvald; Grøndahl, Ragnhild; Hermann, Anne; Dudman, Susanne Gjeruldsen; Müller, Fredrik; Ueland, Thor; Mollnes, Tom Eirik; Aukrust, Pål; Heggelund, Lars; Holten, Aleksander Rygh; Dyrhol-Riise, Anne Ma (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-12-10)
      In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. In this study we analyzed plasma cytokines in COVID-19 patients and investigated their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Hospitalized patients (n = 34) with confirmed COVID-19 were recruited into a ...
    • Increased Local Inflammatory Response to MOC31PE Immunotoxin After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy 

      Thorgersen, Ebbe Billmann; Asvall, Jørund; Frøysnes, Ida Storhaug; Schjalm, Camilla; Larsen, Stein Gunnar; Dueland, Svein; Andersson, Yvonne; Fodstad, Øystein; Mollnes, Tom Eirik; Flatmark, Kjersti (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-05-21)
      Background - Despite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), most patients with resectable peritoneal metastases from colorectal cancer experience disease relapse. MOC31PE immunotoxin is being explored as a novel treatment option for these patients. MOC31PE targets the cancer-associated epithelial cell adhesion molecule, and kills cancer cells by ...
    • Increased thromboinflammatory load in hereditary angioedema 

      Gramstad, Olav Rogde; Schjalm, Camilla; Mollnes, Tom Eirik; Nielsen, Erik Waage (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-08-10)
      C1 inhibitor (C1Inh) is a serine protease inhibitor involved in the kallikrein-kinin system, the complement system, the coagulation system, and the fibrinolytic system. In addition to the plasma leakage observed in hereditary angioedema (HAE), C1Inh deficiency may also affect these systems, which are important for thrombosis and inflammation. The aim of this study was to investigate the thromboinflammatory ...
    • Intracellular Complement Component 3 Attenuated Ischemia-Reperfusion Injury in the Isolated Buffer-Perfused Mouse Heart and Is Associated With Improved Metabolic Homeostasis 

      Torp, May-Kristin; Ranheim, Trine; Schjalm, Camilla; Hjorth, Marit; Heiestad, Christina Mathisen; Dalen, Knut Tomas; Nilsson, Per; Mollnes, Tom Eirik; Pischke, Soeren; Lien, Egil; Vaage, Ingvar Jarle; Yndestad, Arne; Stensløkken, Kåre-Olav (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-01)
      The innate immune system is rapidly activated during myocardial infarction and blockade of extracellular complement system reduces infarct size. Intracellular complement, however, appears to be closely linked to metabolic pathways and its role in ischemia-reperfusion injury is unknown and may be different from complement activation in the circulation. The purpose of the present study was to investigate ...
    • Open chest and pericardium facilitate transpulmonary passage of venous air emboli 

      Storm, Benjamin; Halvorsen, Per Steinar; Skulstad, Helge; Dybwik, Knut Gustav; Schjalm, Camilla; Christiansen, Dorte; Wisløff-Aase, Kristin; Fosse, Erik; Braaten, Tonje Bjørndal; Nielsen, Erik Waage; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-02-17)
      <p><i>Background:</i> Transpulmonary passage of air emboli can lead to fatal brain- and myocardial infarctions. We studied whether pigs with open chest and pericardium had a greater transpulmonary passage of venous air emboli than pigs with closed thorax. <p><i>Methods:</i> We allocated pigs with verified closed foramen ovale to venous air infusion with either open chest with sternotomy and opening ...
    • Properdin binding to complement activating surfaces depends on initial C3b deposition 

      Harboe, Morten; Johnson, Christina; Nymo, Stig Haugset; Ekholt, Karin; Schjalm, Camilla; Lindstad, Julie Katrine; Pharo, Anne Margrethe; Hellerud, Bernt C; Ekdahl, Kristina Nilsson; Mollnes, Tom Eirik; Nilsson, Per (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-01-09)
      Two functions have been assigned to properdin; stabilization of the alternative convertase, C3bBb, is well accepted, whereas the role of properdin as pattern recognition molecule is controversial. The presence of nonphysiological aggregates in purified properdin preparations and experimental models that do not allow discrimination between the initial binding of properdin and binding secondary to C3b ...
    • Rapid systemic surge of IL-33 after severe human trauma: a prospective observational study 

      Sundnes, Olav; Ottestad, William Arne; Schjalm, Camilla; Lundbäck, Peter; La Cour Poulsen, Lars; Mollnes, Tom Eirik; Haraldsen, Guttorm; Eken, Torsten (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-03-26)
      Background - Alarmins are considered proximal mediators of the immune response after tissue injury. Understanding their biology could pave the way for development of new therapeutic targets and biomarkers in human disease, including multiple trauma. In this study we explored high-resolution concentration kinetics of the alarmin interleukin-33 (IL-33) early after human trauma.<p> <p>Methods - ...
    • Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients 

      Holter, Jan Cato; Pischke, Soeren; de Boer, Eline; Lind, Andreas; Jenum, Synne; Holten, Aleksander Rygh; Tonby, Kristian; Barratt-Due, Andreas; Sokolova, Marina; Schjalm, Camilla; Chaban, Viktoriia; Kolderup, Anette; Tran, Trung; Tollefsrud Gjølberg, Torleif; Skeie, Linda Gail; Hesstvedt, Liv; Ormåsen, Vidar; Fevang, Børre; Austad, Cathrine; Muller, Karl Erik; Fladeby, Cathrine; Holberg-Petersen, Mona; Halvorsen, Bente; Müller, Fredrik; Aukrust, Pål; Dudman, Susanne Gjeruldsen; Ueland, Thor; Andersen, Jan Terje; Lund-Johansen, Fridtjof; Heggelund, Lars; Dyrhol-Riise, Anne Ma; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-17)
      The new SARS-CoV-2 pandemic leads to COVID-19 with respiratory failure, substantial morbidity, and significant mortality. Overactivation of the innate immune response is postulated to trigger this detrimental process. The complement system is a key player in innate immunity. Despite a few reports of local complement activation, there is a lack of evidence that the degree of systemic complement ...