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Definition of human apolipoprotein A-I epitopes recognized by autoantibodies present in patients with cardiovascular diseases

Teixeira, Priscila Camillo
Ducret, Axel
Ferber, Philippe
Butterfield, Michelle
Langen, Hanno
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Published in The Journal of biological chemistry. 2014, vol. 289, no. 41, p. 28249-59
Abstract Autoantibodies to apolipoprotein A-I (anti-apoA-I IgG) have been shown to be both markers and mediators of cardiovascular disease, promoting atherogenesis and unstable atherosclerotic plaque. Previous studies have shown that high levels of anti-apoA-I IgGs are independently associated with major adverse cardiovascular events in patients with myocardial infarction. Autoantibody responses to apoA-I can be polyclonal and it is likely that more than one epitope may exist. To identify the specific immunoreactive peptides in apoA-I, we have developed a set of methodologies and procedures to isolate, purify, and identify novel apoA-I endogenous epitopes. First, we generated high purity apoA-I from human plasma, using thiophilic interaction chromatography followed by enzymatic digestion specifically at lysine or arginine residues. Immunoreactivity to the different peptides generated was tested by ELISA using serum obtained from patients with acute myocardial infarction and high titers of autoantibodies to native apoA-I. The immunoreactive peptides were further sequenced by mass spectrometry. Our approach successfully identified two novel immunoreactive peptides, recognized by autoantibodies from patients suffering from myocardial infarction, who contain a high titer of anti-apoA-I IgG. The discovery of these epitopes may open innovative prognostic and therapeutic opportunities potentially suitable to improve current cardiovascular risk stratification.
Keywords Amino Acid SequenceApolipoprotein A-I/chemistry/immunologyAtherosclerosis/immunologyAutoantibodies/biosynthesis/bloodBiological Markers/analysisChromatography, AffinityEnzyme-Linked Immunosorbent AssayEpitopes/chemistry/immunologyGene ExpressionHumansImmunoglobulin G/biosynthesis/bloodMolecular Sequence DataMyocardial Infarction/blood/diagnosis/immunology/pathologyPeptides/chemistry/immunologyPlaque, Atherosclerotic/blood/diagnosis/immunology/pathologySequence Analysis, Protein
PMID: 25170076
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Research groups Chimie et protéomique clinique (270)
Hiv (835)
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TEIXEIRA, Priscila Camillo et al. Definition of human apolipoprotein A-I epitopes recognized by autoantibodies present in patients with cardiovascular diseases. In: The Journal of biological chemistry, 2014, vol. 289, n° 41, p. 28249-59. doi: 10.1074/jbc.M114.589002 https://archive-ouverte.unige.ch/unige:55615

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Deposited on : 2015-04-20

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