The alternative complement pathway is dysregulated in patients with chronic heart failure.

Abstract

The complement system, an important arm of the innate immune system, is activated in heart failure (HF). We hypothesized that HF patients are characterized by an imbalance of alternative amplification loop components; including properdin and complement factor D and the alternative pathway inhibitor factor H. These components and the activation product, terminal complement complex (TCC), were measured in plasma from 188 HF patients and 67 age- and sex- matched healthy controls by enzyme immunoassay. Our main findings were: (i) Compared to controls, patients with HF had significantly increased levels of factor D and TCC, and decreased levels of properdin, particularly patients with advanced clinical disorder (i.e., NYHA functional class IV), (ii) Levels of factor D and properdin in HF patients were correlated with measures of systemic inflammation (i.e., C-reactive protein), neurohormonal deterioration (i.e., Nt-proBNP), cardiac function, and deteriorated diastolic function, (iii) Low levels of factor H and properdin were associated with adverse outcome in univariate analysis and for factor H, this was also seen in an adjusted model. Our results indicate that dysregulation of circulating components of the alternative pathway explain the increased degree of complement activation and is related to disease severity in HF patients.

Authors

Negar Shahini, Annika E Michelsen, Per H Nilsson, Karin Ekholt, Lars Gullestad, Kaspar Broch, Christen P Dahl, Pål Aukrust, Thor Ueland, Tom Eirik Mollnes, Arne Yndestad, Mieke C Louwe

Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.