• 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 ...
    • 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 ...
    • Cholesterol Crystals Induce coagulation Activation through Complement-Dependent Expression of Monocytic Tissue Factor 

      Gravastrand, Caroline S.; Steinkjer, Bjørg; Halvorsen, Bente; Landsem, Anne; Skjelland, Mona; Jacobsen, Eva Astrid; Woodruff, Trent M.; Lambris, John D.; Mollnes, Tom Eirik; Brekke, Ole-Lars; Espevik, Terje; Rokstad, Anne Mari (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-07-03)
      Cholesterol crystals (CC) are strong activators of complement and could potentially be involved in thromboinflammation through complement-coagulation cross-talk. To explore the coagulation-inducing potential of CC, we performed studies in lepirudin-based human whole blood and plasma models. In addition, immunohistological examinations of brain thrombi and vulnerable plaque material from patients ...
    • 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 ...
    • Circulating T Cell Activation and Exhaustion Markers Are Associated With Radiation Pneumonitis and Poor Survival in Non-Small-Cell Lung Cancer 

      Berg, Janna; Halvorsen, Ann Rita; Bengtson, May-Bente; Lindberg, Morten; Halvorsen, Bente; Aukrust, Pål; Helland, Åslaug; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-14)
      Introduction: Persistent inflammation and immune activation in the lungs are associated with adverse outcomes such as radiation pneumonitis (RP) and poor survival in non-small-cell lung cancer (NSCLC) patients. However, it is unknown how this is reflected by leukocyte activation markers in serum.<p> <p>Objective: The aim was to evaluate the serum levels of activation of different leukocyte subsets ...
    • 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, ...
    • Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab 

      Woxholt, Sindre; Ueland, Thor; Aukrust, Pål; Anstensrud, Anne Kristine; Broch, Kaspar; Tøllefsen, Ingvild Maria; Ryan, Liv; Bendz, Bjørn; Hopp, Einar; Kløw, Nils-Einar; Seljeflot, Ingebjørg; Halvorsen, Bente; Dahl, Tuva Børresdatter; Huse, Camilla; Andersen, Geir Øystein; Gullestad, Lars; Wiseth, Rune; Amundsen, Brage H.; Damås, Jan Kristian; Kleveland, Ola (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-08-17)
      Background - Tocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and their correlations with neutrophils, C-reactive protein (CRP), troponin T, MSI and infarct size.<p> <p>Methods - STEMI patients were randomised to receive a single ...
    • Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID‑19 (Bari‑SolidAct): a randomised, double‑blind, placebo‑controlled phase 3 trial 

      Trøseid, Marius; Arribas, José R.; Assoumou, Lambert; Holten, Aleksander Rygh; Poissy, Julien; Terzic, Vida; Mazzaferri, Fulvia; Baño, Jesús Rodríguez; Eustace, Joe; Hites, Maya; Joannidis, Michael; Paiva, José-Artur; Reuter, Jean; Püntmann, Isabel; Patrick-Brown, Thale Dawn; Westerheim, Elin; Nezvalova-Henriksen, Katerina; Beniguel, Lydie; Dahl, Tuva Børresdatter; Bouscambert, Maude; Halanova, Monika; Péterfi, Zoltán; Tsiodras, Sotirios; Rezek, Michael; Briel, Matthias; Ünal, Serhat; Schlegel, Martin; Ader, Florence; Lacombe, Karine; Amdal, Cecilie Delphin; Rodrigues, Serge; Tonby, Kristian; Gaudet, Alexandre; Heggelund, Lars; Mootien, Joy; Johannessen, Asgeir; Møller, Jannicke Horjen; Pollan, Beatriz Diaz; Tveita, Anders Aune; Kildal, Anders Benjamin; Richard, Jean-Christophe; Dalgard, Olav; Simensen, Victoria Charlotte; Baldé, Aliou; de Gastines, Lucie; del Álamo, Marta; Aydin, Burç; Lund-Johansen, Fridtjof; Trabaud, Mary-Anne; Diallo, Alpha; Halvorsen, Bente; Røttingen, John-Arne; Tacconelli, Evelina; Yazdanpanah, Yazdan; Olsen, Inge Christoffer; Costagliola, Dominique; Study Group, EU-SolidAct (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-01-10)
      Background Baricitinib has shown efcacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifcally on severe/critical COVID, including vaccinated participants.<p> <p>Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external ...
    • 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 ...
    • Endonuclease v regulates atherosclerosis through c-c motif chemokine ligand 2-mediated monocyte infiltration 

      Kong, Xiang Yi; Huse, Camilla; Yang, Kuan; Øgaard, Jonas; Jimenez, Natalia Berges; Vik, Erik Sebastian; Nawaz, Meh Sameen; Quiles-Jiménez, Ana M T; Abbas, Azhar; Gregersen, Ida; Holm, Sverre; Bjerkli, Vigdis; Rashidi, Azita; Fladeby, Cathrine; Suganthan, Rajikala; Sagen, Ellen Lund; Skjelland, Mona; Lång, Anna; Bøe, Stig Ove; Bjørås, Magnar; Aukrust, Pål; Alseth, Ingrun; Halvorsen, Bente; Dahl, Tuva Børresdatter (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-07-14)
      BACKGROUND: In cardiovascular diseases, atherosclerotic disorder are the most frequent and important with respect to morbidity and mortality. Inflammation mediated by immune cells is central in all parts of the atherosclerotic progress, and further understanding of the underlying mechanisms is needed. Growing evidence suggests that deamination of adenosine-toinosine in RNA is crucial for a correct ...
    • Gut microbiota-dependent trimethylamine N-oxide associates with inflammation in common variable immunodeficiency 

      Macpherson, Magnhild Eide; Hov, Johannes Espolin Roksund; Ueland, Thor; Dahl, Tuva Børresdatter; Kummen, Martin; Otterdal, Kari; Holm, Kristian; Berge, Rolf Kristian; Mollnes, Tom Eirik; Trøseid, Marius; Halvorsen, Bente; Aukrust, Pål; Fevang, Børre; Jørgensen, Silje Fjellgård (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-09-16)
      A substantial proportion of patients with common variable immunodeficiency (CVID) have inflammatory and autoimmune complications of unknown etiology. We have previously shown that systemic inflammation in CVID correlates with their gut microbial dysbiosis. The gut microbiota dependent metabolite trimethylamine N-oxide (TMAO) has been linked to several metabolic and inflammatory disorders, but has ...
    • IL-18 and IL-18 binding protein are related to disease severity and parasitemia during falciparum malaria 

      Otterdal, Kari; Berg, Åse; Michelsen, Annika Elisabet; Yndestad, Arne; Patel, Sam; Gregersen, Ida; Halvorsen, Bente; Ueland, Thor; Langeland, Nina; Aukrust, Pål (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-10-18)
      Background - Several inflammatory molecules participate in the immune response to malaria. Interleukin (IL)-18 is an inflammatory cytokine activated by NLRP3 inflammasomes. In clinical falciparum malaria, with and without HIV co-infection, data on IL-18 and in particular on its binding protein, IL-18bp, is scarce.<p> <p>Methods - Clinical data and blood samples were collected from adults in ...
    • 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 ...
    • Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia 

      Holm, Sverre; Kared, Hassen; Michelsen, Annika Elisabet; Kong, Xiang Yi; Dahl, Tuva Børresdatter; Schultz, Nina Haagenrud; Nyman, Tuula Anneli; Fladeby, Cathrine; Seljeflot, Ingebjørg; Ueland, Thor; Stensland, Maria; Mjaaland, Siri; Goll, Guro Løvik; Nissen-Meyer, Lise Sofie Haug; Aukrust, Pål; Skagen, Karolina Ryeng; Gregersen, Ida; Skjelland, Mona; Holme, Pål Andre; Munthe, Ludvig Andre; Halvorsen, Bente (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-08-18)
      Aims - We recently reported five cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) 7–10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against corona virus disease 2019 (COVID-19). We aimed to investigate the pathogenic immunological responses operating in these patients.<p> <p>Methods and results - We assessed circulating inflammatory markers ...
    • Impaired HDL function amplifies systemic inflammation in common variable immunodeficiency 

      Macpherson, Magnhild Eide; Halvorsen, Bente; Yndestad, Arne; Ueland, Thor; Mollnes, Tom Eirik; Berge, Rolf Kristian; Rashidi, Azita; Otterdal, Kari; Gregersen, Ida; Kong, Xiang Yi; Holven, Kirsten Bjørklund; Aukrust, Pål; Fevang, Børre; Jørgensen, Silje Fjellgård (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-07-01)
      Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency, characterized by inadequate antibody responses and recurrent bacterial infections. Paradoxically, a majority of CVID patients have non-infectious inflammatory and autoimmune complications, associated with systemic immune activation. Our aim was to explore if HDL, known to have anti-inflammatory properties, ...
    • Increased Systemic and Local Interleukin 9 Levels in Patients with Carotid and Coronary Atherosclerosis 

      Gregersen, Ida; Skjelland, Mona; Holm, Sverre; Holven, Kirsten Bjørklund; Sørensen, Kirsten; Russell, David; Askevold, Erik Tandberg; Dahl, Christen Peder; Ørn, Stein; Gullestad, Lars; Mollnes, Tom Eirik; Ueland, Thor; Aukrust, Pål; Halvorsen, Bente (Journal article; Tidsskriftartikkel; Peer reviewed, 2013)
      Objective: Atherosclerosis is a chronic inflammatory disorder that involves a range of inflammatory mediators. Although interleukin (IL)-9 has been related to inflammation, there are at present no data on its role in atherosclerosis. Here we have examined IL-9 and IL-9 receptor (IL-9R) systemically and locally in patients with coronary and carotid atherosclerosis. Methods: Plasma IL-9 was quantified ...
    • Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial 

      Huse, Camilla; Anstensrud, Anne Kristine; Michelsen, Annika Elisabet; Ueland, Thor; Broch, Kaspar; Woxholt, Sindre; Yang, Kuan; Sharma, Kapil Kishore; Tøllefsen, Ingvild Maria; Bendz, Bjørn; Amundsen, Brage H.; Damås, Jan Kristian; Berg, Erlend Sturle; Bjørkelund, Elisabeth; Quiles-Jiménez, Ana M T; Bjerkeli, Vigdis; Bendz, Christina; Kleveland, Ola; Stensæth, Knut Haakon; Opdahl, Anders; Kløw, Nils-Einar; Andersen, Geir Øystein; Wiseth, Rune; Halvorsen, Bente; Gullestad, Lars; Seljeflot, Ingebjørg; Aukrust, Pål; Osnes, Liv T. N.; Dahl, Tuva Børresdatter (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-30)
      Background We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear.<p> <p>Methods In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI ...
    • Interleukin-6 receptor inhibition with tocilizumab induces a selective and substantial increase in plasma IP-10 and MIP-1β in non-ST-elevation myocardial infarction 

      Kleveland, Ola; Ueland, Thor; Kunszt, Gabor; Bratlie, Marte; Yndestad, Arne; Broch, Kaspar; Holte, Espen; Ryan, Liv; Amundsen, Brage H.; Bendz, Bjørn; Aakhus, Svend; Espevik, Terje; Halvorsen, Bente; Mollnes, Tom Eirik; Wiseth, Rune; Gullestad, Lars; Aukrust, Pål; Damås, Jan Kristian (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-06-29)
      <p><i>Aim</i>: To evaluate the effect of interleukin-6 inhibition with tocilizumab on the cytokine network in patients with acute non-ST-elevation myocardial infarction (NSTEMI).</p> <p><i>Methods</i>: 117 patients with acute NSTEMI were randomised to an intravenous infusion of 280 mg tocilizumab or placebo prior to coronary angiography. Blood samples were obtained at baseline, at 6 consecutive ...
    • Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure 

      Nendl, Andraz; Raju, Sajan; Broch, Kaspar; Mayerhofer, Christiane Caroline; Holm, Kristian; Halvorsen, Bente; Lappegård, Knut Tore; Moscavitch, Samuel; Hov, Johannes Espolin Roksund; Seljeflot, Ingebjørg; Trøseid, Marius; Awoyemi, Ayodeji Olawale (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-06-02)
      Background: The gut microbiota in patients with chronic heart failure (HF) is characterized by low bacterial diversity and reduced ability to synthesize beneficial metabolites. These changes may facilitate leakage of whole bacteria or bacterial products from the gut into the bloodstream, which may activate the innate immune system and contribute to the low-grade inflammation seen in HF. In this ...
    • Legumain in Acute Coronary Syndromes: A Substudy of the PLATO (Platelet Inhibition and Patient Outcomes) Trial 

      Gregersen, Ida; Michelsen, Annika; Lunde, Ngoc Nguyen; Åkerblom, Axel; Lakic, Tatevik G.; Skjelland, Mona; Skagen, Karolina Ryeng; Becker, Richard C.; Lindbäck, Johan; Himmelmann, Anders; Solberg, Rigmor; Johansen, Harald Thidemann; James, Stefan K.; Siegbahn, Agneta; Storey, Robert F.; Kontny, Frederic; Aukrust, Pål; Ueland, Thor; Wallentin, Lars; Halvorsen, Bente (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-08-15)
      <i>Background</i> - The cysteine protease legumain is increased in patients with atherosclerosis, but its causal role in atherogenesis and cardiovascular disease is still unclear. The aim of the study was to investigate the association of legumain with clinical outcome in a large cohort of patients with acute coronary syndrome.<p><p> <i>Methods and Results</i> - Serum levels of legumain were ...