Aim: Animal studies suggested that silencing of complement genes, mainly those from the alternative pathway, may affect their lipid metabolism. In a human observational cohort, we now investigated the associations of the alternative complement pathway components [i.e. C3, C3a, Bb, factor D, factor H, properdin, and MASP-3], with lipoprotein profiles measured by nuclear magnetic resonance spectroscopy (1H-NMR). 

Methods: Complement components and 1H-NMR spectra were obtained in 523 participants (60±7 years, 61% men) of the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study. Multiple linear regression analyses were used to investigate associations of plasma complement concentrations with concentrations of 14 individual lipoprotein subclasses, ranging from very large VLDL to small HDL, as well as the mean particle size of the major lipoprotein classes (all standardized [std] values).

Results: Participants with higher C3 concentrations had more circulating VLDLs (stdβs from 0.36 for very large VLDL to 0.27 for very small VLDL), IDL/LDLs (stdβs from 0.14 for IDL to 0.16 for small LDL), and small HDL (stdβ=0.21) and had, in contrast, fewer larger HDL particles (stdβs= –0.36 for very large and large HDL), all false discovery rate corrected P-value <0.05. We observed similar but weaker associations for the components and regulators of alternative pathway activation (i.e. Factor D, Factor H, properdin, and MASP-3), but not for the activated products (C3a and Bb).

Conclusion: The alternative complement pathway, and most prominently C3, is associated with an adverse lipid profile that characterized by more triglyceride-enriched lipoproteins and fewer large HDL.

03 - THE ALTERNATIVE COMPLEMENT PATHWAY IS ASSOCIATED WITH AN ADVERSE LIPID PROFILE: THE CODAM STUDY