• Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock 

      Orrem, Hilde L.; Nilsson, Per H.; Pischke, Søren Erik; Grindheim, Guro; Garred, Peter; Seljeflot, Ingebjørg; Husebye, Trygve; Aukrust, Pål; Yndestad, Arne; Andersen, Geir Ø.; Barratt-Due, Andreas; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-02-09)
      Aims: Heart failure (HF) is an impending complication to myocardial infarction. We hypothesized that the degree of complement activation reflects severity of HF following acute myocardial infarction. <br> <br> Methods and results: The LEAF trial (LEvosimendan in Acute heart Failure following myocardial infarction) evaluating 61 patients developing HF within 48 h after percutaneous coronary ...
    • Anti-PF4/polyanion antibodies in COVID-19 patients are associated with disease severity and pulmonary pathology 

      Ueland, Thor; Sørvoll, Ingvild Hausberg; Mørtberg, Trude Victoria; Dahl, Tuva Børresdatter; Lerum, Tøri Vigeland; Michelsen, Annika Elisabet; Ranheim, Trine; Nezvalova-Henriksen, Katerina; Dyrhol-Riise, Anne Ma; Holme, Pål Andre; Aaløkken, Trond Mogens; Skjønsberg, Ole Henning; Barratt-Due, Andreas; Ahlen, Maria Therese; Aukrust, Pål; Halvorsen, Bente (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-02-28)
      Thromboembolic events are frequent and associated with poor outcome in severe COVID-19 disease. Anti-PF4/polyanion antibodies are related to heparin-induced thrombocytopenia (HIT) and thrombus formation, but data on these antibodies in unselected COVID-19 populations are scarce. We assessed the presence of anti-PF4/polyanion antibodies in prospectively collected serum from an unselected cohort ...
    • Circulating markers of extracellular matrix remodelling in severe COVID-19 patients 

      Murphy, Sarah Louise Mikalsen; Halvorsen, Bente; Holter, Jan Cato; Huse, Camilla; Tveita, Anders; Trøseid, Marius; Hoel, Hedda; Kildal, Anders Benjamin; Holten, Aleksander Rygh; Lerum, Tøri Vigeland; Skjønsberg, Ole Henning; Michelsen, Annika Elisabet; Aaløkken, Trond Mogens; Tonby, Kristian; Lind, Andreas; Dudman, Susanne Gjeruldsen; Granerud, Beathe Kiland; Heggelund, Lars; Bøe, Simen; Dyrholt-Riise, Anne Ma; Aukrust, Pål; Barratt-Due, Andreas; Ueland, Thor; Dahl, Tuva Børresdatter (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-09-17)
      Background Abnormal remodelling of the extracellular matrix (ECM) has generally been linked to pulmonary inflammation and fibrosis and may also play a role in the pathogenesis of severe COVID-19. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID-19, we examined circulating levels of mediators involved in various aspects of these processes in COVID-19 ...
    • Coagulopathy and adverse outcomes in hospitalized patients with COVID-19: results from the NOR-Solidarity trial 

      Ueland, Thor; Michelsen, Annika Elisabet; Tveita, Anders; Kåsine, Trine; Dahl, Tuva Børresdatter; Finbråten, Ane-Kristine; Holten, Aleksander Rygh; Skjønsberg, Ole Henning; Mathiessen, Alexander; Nezvalova-Henriksen, Katerina; Trøseid, Marius; Aaløkken, Trond Mogens; Halvorsen, Bente; Dyrhol-Riise, Anne Ma; Barratt-Due, Andreas; Aukrust, Pål (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-12-07)
      Background - Several studies have examined parameters of increased thrombogenicity in COVID-19, but studies examining their association with long-term outcome and potential effects of antiviral agents in hospitalized patients with COVID-19 are scarce.<p> <p>Objectives - To evaluate plasma levels of hemostatic proteins during hospitalization in relation to disease severity, treatment modalities, ...
    • 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 ...
    • 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 ...
    • Combined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsis 

      Skjeflo, Espen Waage; Sagatun, Caroline; Dybwik, Knut; Aam, Sturla; Urving, Sven Haakon; Nunn, Miles A.; Fure, Hilde; Lau, Corinna; Brekke, Ole Lars; Huber-Lang, Markus; Barratt-Due, Andreas; Nielsen, Erik Waage; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-11-27)
      Introduction: Sepsis is an exaggerated and dysfunctional immune response to infection. Activation of innate immunity recognition systems including complement and the Toll-like receptor family initiate this disproportionate inflammatory response. The aim of this study was to explore the effect of combined inhibition of the complement component C5 and the Toll-like receptor co-factor CD14 on survival, ...
    • 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 factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function 

      Pischke, Søren Erik; Gustavsen, Alice; Orrem, Hilde Lang; Egge, Kjetil Hagene; Courivaud, Frederic A. A.; Fontenelle, Hugues; Despont, Alain; Bongoni, Anjan K.; Rieben, Robert; Tønnessen, Tor Inge; Nunn, Miles A.; Scott, Helge; Skulstad, Helge; Barratt-Due, Andreas; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-03-03)
      Inhibition of complement factor 5 (C5) reduced myocardial infarction in animal studies, while no benefit was found in clinical studies. Due to lack of cross-reactivity of clinically used C5 antibodies, different inhibitors were used in animal and clinical studies. Coversin (Ornithodoros moubata complement inhibitor, OmCI) blocks C5 cleavage and binds leukotriene B4 in humans and pigs. We hypothesized ...
    • Complement in clinical medicine: Clinical trials, case reports and therapy monitoring 

      Ricklin, Daniel; Barratt-Due, Andreas; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-05-31)
      Research during past decades made it evident that complement is involved in more tasks than fighting infections, but has important roles in other immune surveillance and housekeeping functions. If the balance between complement activation and regulation is out of tune, however, complement can quickly turn against the host and contribute to adverse processes that result in various clinical conditions. ...
    • Dual inhibition of complement and Toll-like receptors as a novel approach to treat inflammatory diseases-C3 or C5 emerge together with CD14 as promising targets. 

      Barratt-Due, Andreas; Pischke, Søren Erik; Nilsson, Per; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-08-31)
      The host is protected by pattern recognition systems, including complement and TLRs, which are closely cross-talking. If improperly activated, these systems might induce tissue damage and disease. Inhibition of single downstream proinflammatory cytokines, such as TNF, IL-1β, and IL-6, have failed in clinical sepsis trials, which might not be unexpected, given the substantial amounts of mediators ...
    • 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 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 ...
    • Elevated plasma sTIM-3 levels in patients with severe COVID-19 

      Ueland, Thor; Heggelund, Lars; Lind, Andreas; Holten, Aleksander Rygh; Tonby, Kristian; Michelsen, Annika; Jenum, Synne; Jørgensen, Marthe Jøntvedt; Barratt-Due, Andreas; Skeie, Linda Gail; Nordøy, Ingvild; Aanensen Fraz, Mai Sasaki; Paulsen, Else Quist; Pischke, Soeren; Johal, Simreen Kaur; Hesstvedt, Liv; Bogen, Mette; Fevang, Børre; Halvorsen, Bente; Müller, Fredrik; Bekken, Gry Kloumann; Mollnes, Tom Eirik; Dudman, Susanne Gjeruldsen; Aukrust, Pål; Dyrhol-Riise, Anne Ma; Holter, Jan Cato (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-21)
      <i>Background</i> - The pathogenesis of coronavirus disease 2019 (COVID-19) is still incompletely understood, but it seems to involve immune activation and immune dysregulation.<p> <p><i>Objective</i> - We examined the parameters of activation of different leukocyte subsets in COVID-19–infected patients in relation to disease severity.<p> <p><i>Methods</i> - We analyzed plasma levels of ...
    • High circulating levels of the homeostatic chemokines CCL19 and CCL21 predict mortality and disease severity in Covid-19 

      Tveita, Anders Aune; Murphy, Sarah Louise Mikalsen; Holter, Jan Cato; Kildal, Anders Benjamin; Michelsen, Annika Elisabet; Lerum, Tøri Vigeland; Kaarbø, Mari; Heggelund, Lars; Holten, Aleksander Rygh; Finbråten, Ane-Kristine; Muller, Karl Erik; Mathiessen, Alexander; Bøe, Simen; Fevang, Børre; Granerud, Beathe Kiland; Tonby, Kristian; Lind, Andreas; Dudman, Susanne; Nezvalova-Henriksen, Katerina; Müller, Fredrik; Skjønsberg, Ole Henning; Trøseid, Marius; Barratt-Due, Andreas; Riise, Anne Margarita Dyrhol; Aukrust, Pål; Halvorsen, Bente Evy; Dahl, Tuva Børresdatter; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-25)
      Background. Immune dysregulation is a major factor in the development of severe coronavirus disease 2019 (COVID-19). The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited. We thus investigated the levels of these chemokines in COVID-19 ...
    • IL-6 receptor inhibition by tocilizumab attenuated expression of C5a receptor 1 and 2 in non-ST-elevation myocardial infarction 

      Orrem, Hilde Lang; Nilsson, Per; Pischke, Søren Erik; Kleveland, Ola; Yndestad, Arne; Ekholt, Karin; Damås, Jan Kristian; Espevik, Terje; Bendz, Bjørn; Halvorsen, Bente; Gregersen, Ida; Wiseth, Rune; Andersen, Geir Øystein; Ueland, Thor; Gullestad, Lars; Aukrust, Pål; Barratt-Due, Andreas; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-09-12)
      <p><i>Background</i>: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL-6 receptor (IL-6R)-antagonist tocilizumab on the expression of the ...
    • Persistent pulmonary pathology after COVID-19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase-9 

      Lerum, Tøri Vigeland; Maltzahn, Niklas; Aukrust, Pål; Trøseid, Marius; Nezvalova-Henriksen, Katerina; Kåsine, Trine; Dyrhol-Riise, Anne Ma; Stiksrud, Birgitte; Haugli, Mette; Blomberg, Bjørn; Kittang, Bård Reiakvam; Johannessen, Asgeir; Hannula, Raisa; Aballi, Saad; Kildal, Anders Benjamin; Eiken, Ragnhild; Dahl, Tuva Børresdatter; Lund-Johansen, Fridtjof; Müller, Fredrik; Rivero, Jezabel Rodriguez; Meltzer, Carin; Einvik, Gunnar; Ueland, Thor; Olsen, Inge Christoffer; Barratt-Due, Andreas; Aaløkken, Trond Mogens; Skjønsberg, Ole Henning (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-01)
      The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DL<sub>CO</sub>), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, ...
    • Persistent T-cell exhaustion in relation to prolonged pulmonary pathology and death after severe COVID-19: Results from two Norwegian cohort studies 

      Trøseid, Marius; Dahl, Tuva Børresdatter; Holter, Jan Cato; Kildal, Anders Benjamin; Murphy, Sarah Louise Mikalsen; Yang, Kuan; Quiles Jimenez, Ana Maria Teresa; Heggelund, Lars; Muller, Karl Erik; Tveita, Anders Aune; Michelsen, Annika Elisabet; Bøe, Simen; Holten, Aleksander Rygh; Hoel, Hedda Benedicte; Mathiessen, Alexander; Aaløkken, Trond Mogens; Fevang, Børre; Granerud, Beathe Kiland; Tonby, Kristian; Nezvalova-Henriksen, Katerina; Lerum, Tøri Vigeland; Müller, Fredrik; Skjønsberg, Ole Henning; Barratt-Due, Andreas; Riise, Anne Margarita Dyrhol; Aukrust, Pål; Halvorsen, Bente Evy; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-08-18)
      Background - T-cell activation is associated with an adverse outcome in COVID-19, but whether T-cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown.<p> <p>Objectives - To investigate whether T-cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID-19.<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 ...