• Combined inhibition of complement and CD14 attenuates bacteria-induced inflammation in human whole blood more efficiently than antagonizing the toll-like receptor 4-MD2 complex 

      Gustavsen, Alice; Nymo, Stig Haugset; Landsem, Anne; Christiansen, Dorte; Ryan, Liv; Husebye, Harald; Lau, Corinna; Pischke, Søren Erik; Lambris, John D.; Espevik, Terje; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2016-03-14)
      <i>Background</i>: Single inhibition of the Toll-like receptor 4 (TLR4)–MD2 complex failed in treatment of sepsis. CD14 is a coreceptor for several TLRs, including TLR4 and TLR2. The aim of this study was to investigate the effect of single TLR4-MD2 inhibition by using eritoran, compared with the effect of CD14 inhibition alone and combined with the C3 complement inhibitor compstatin (Cp40), on the ...
    • 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 ...
    • 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 ...