Frontiers in Immunology (Dec 2021)

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

  • Margrethe Flesvig Holt,
  • Margrethe Flesvig Holt,
  • Annika E. Michelsen,
  • Annika E. Michelsen,
  • Negar Shahini,
  • Elisabeth Bjørkelund,
  • Christina Holt Bendz,
  • Richard J. Massey,
  • Richard J. Massey,
  • Camilla Schjalm,
  • Bente Halvorsen,
  • Bente Halvorsen,
  • Kaspar Broch,
  • Kaspar Broch,
  • Thor Ueland,
  • Thor Ueland,
  • Thor Ueland,
  • Lars Gullestad,
  • Lars Gullestad,
  • Lars Gullestad,
  • Per H. Nilsson,
  • Per H. Nilsson,
  • Pål Aukrust,
  • Pål Aukrust,
  • Pål Aukrust,
  • Tom Eirik Mollnes,
  • Tom Eirik Mollnes,
  • Tom Eirik Mollnes,
  • Tom Eirik Mollnes,
  • Mieke C. Louwe

DOI
https://doi.org/10.3389/fimmu.2021.800978
Journal volume & issue
Vol. 12

Abstract

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ObjectiveDysregulation 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 HF.MethodsWe analyzed plasma levels of FB, C3bBbP, and terminal C5b-9 complement complex (TCC) in 343 HF patients and 27 healthy controls.ResultsCompared with controls, patients with HF had elevated levels of circulating FB (1.6-fold, p < 0.001) and C3bBbP (1.3-fold, p < 0.001). In contrast, TCC, reflecting the terminal pathway, was not significantly increased (p = 0.15 vs controls). FB was associated with NT-proBNP, troponin, eGFR, and i.e., C-reactive protein. FB, C3bBbP and TCC were not associated with mortality in HF during a mean follow up of 4.3 years.ConclusionOur findings suggest that in patients with HF, the alternative pathway is activated. However, this is not accompanied by activation of the terminal pathway.

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