Nicolas Vuilleumier, Switzerland
HUG/Geneva University Medical Faculty Diagnostic Departement/Department of internal medicine specialities
Presenter of 2 Presentations
Live Q&A
Session Time
12:00 - 13:00
Lecture Time
12:20 - 12:35
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Antibodies against the c-terminus of apolipoprotein A-1 as predictors of death in the general population but not as therapeutic targets actionable through cognate peptides immunomodulation.
Session Time
12:00 - 13:00
Lecture Time
12:10 - 12:15
Background and Aims
Autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgGs) have emerged as an independent biomarker for cardiovascular disease and mortality in humans, promote death in ApoE -/- mice, and seem to be preferentially oriented against the c-terminal part of apoA-1 (cterA1). Corresponding specific mimetic peptides were shown to reverse anti-apoA-1 IgG pro-inflammatory effects in vitro. We evaluated the association of IgG against c-terminus apoA-1 (anti-cterA1 IgGs) with all-cause mortality in the community and tested the ability of two cterA1 mimetic peptides to reverse the anti-apoA-1 IgG-induced inflammation in vitro and mortality in ApoE -/- mice.
Methods
Anti-cterA1 IgGs were measured on serum samples of 5220 consecutive participants included in the CoLaus study with median follow-up duration of 5.6 years. The primary study outcome was all-cause mortality. Two chemically engineered optimized cterA1 mimetic peptides were tested i) on HEK cells to modulate interleukin-8 (IL-8) and tumor necrosis-alpha (TNF-α) production, and ii) in apoE -/- mice exposed to 16 weeks of anti-apoA-1 IgG passive immunisation.
Results
Anti-cterA1 IgG independently predicted all-cause mortality, each standard deviation of anti-cterA1 IgG being associated with a 18% increase in mortality risk (Hazard Ratio:1.18, 95%confidence intervals:1.04-1.33;p=0.009). Both cterA1 mimetic peptides reduced the anti-apoA-1 IgG-induced inflammation in a dose-dependent manner in vitro, but did not rescue the anti-apoA-1 IgG-associated mortality in mice.
Conclusions
Anti-cterA1 IgG independently predict all-cause mortality in the general population. By failing to reverse the anti-apoA-1 IgG-induced mortality in mice, our data do not support the hypothesis that these autoantibodies could be actionable through cognate peptides immunomodulation.
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