The Human Autoantibody Response to Apolipoprotein A-I Is Focused on the C-Terminal Helix: A New Rationale for Diagnosis and Treatment of Cardiovascular Disease?

Abstract

BACKGROUND:

Cardiovascular disease (CVD) is the leading cause of death worldwide and new approaches for both diagnosis and treatment are required. Autoantibodies directed against apolipoprotein A-I (ApoA-I) represent promising biomarkers for use in risk stratification of CVD and may also play a direct role in pathogenesis.

METHODOLOGY:

To characterize the anti-ApoA-I autoantibody response, we measured the immunoreactivity to engineered peptides corresponding to the different alpha-helical regions of ApoA-I, using plasma from acute chest pain cohort patients known to be positive for anti-ApoA-I autoantibodies.

PRINCIPAL FINDINGS:

Our results indicate that the anti-ApoA-I autoantibody response is strongly biased towards the C-terminal alpha-helix of the protein, with an optimized mimetic peptide corresponding to this part of the protein recapitulating the diagnostic accuracy for an acute ischemic coronary etiology (non-ST segment elevation myocardial infarction and unstable angina) obtainable using intact endogenous ApoA-I in immunoassay. Furthermore, the optimized mimetic peptide strongly inhibits the pathology-associated capacity of anti-ApoA-I antibodies to elicit proinflammatory cytokine release from cultured human macrophages.

CONCLUSIONS:

In addition to providing a rationale for the development of new approaches for the diagnosis and therapy of CVD, our observations may contribute to the elucidation of how anti-ApoA-I autoantibodies are elicited in individuals without autoimmune disease.

• Authors: Sabrina Pagano, Hubert Gaertner, Fabrice Cerini, Tiphaine Mannic, Nathalie Satta, Priscila Camillo Teixeira, Paul Cutler, François Mach, Nicolas Vuilleumier, Oliver Hartley
• Journal: PloS one (PLoS One) Vol. 10 Issue 7 Pg. e0132780 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26177543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• APOA1 protein, human
• Apolipoprotein A-I
• Autoantibodies
• Immobilized Proteins
• Immunoglobulin G
• Inflammation Mediators
• Interleukin-6
• Peptides
• Tumor Necrosis Factor-alpha

Topics

• Amino Acid Sequence
• Apolipoprotein A-I (chemistry, immunology)
• Autoantibodies (immunology)
• Cardiovascular Diseases (blood, diagnosis, therapy)
• Circular Dichroism
• Humans
• Immobilized Proteins (metabolism)
• Immunoglobulin G (metabolism)
• Inflammation Mediators (metabolism)
• Interleukin-6 (pharmacology)
• Molecular Sequence Data
• Peptides (chemistry)
• Protein Engineering
• Protein Structure, Secondary
• Tumor Necrosis Factor-alpha (pharmacology)