Identification of Immune Responses Against Aldehyde-Modified Peptide Sequences in ApoB Associated With Cardiovascular Disease

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 23; no. 5; pp. 872 - 878
• Main Authors: Fredrikson, Gunilla Nordin, Hedblad, Bo, Berglund, Göran, Alm, Ragnar, Ares, Mikko, Cercek, Bojan, Chyu, Kuang-Yuh, Shah, Prediman K., Nilsson, Jan
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.05.2003; Hagerstown, MD Lippincott
• Subjects: Age Factors; Aged; Amino Acid Sequence; Antibody Specificity; Apolipoprotein B-100; apolipoproteins; Apolipoproteins B - chemistry; Apolipoproteins B - immunology; atherosclerosis; Atherosclerosis (general aspects, experimental research); Autoantibodies - blood; Biological and medical sciences; Blood and lymphatic vessels; Cardiac and Cardiovascular Systems; Cardiology and Cardiovascular Disease; Cardiology. Vascular system; cardiovascular diseases; Carotid Stenosis - blood; Carotid Stenosis - diagnostic imaging; Carotid Stenosis - immunology; Carotid Stenosis - pathology; Case-Control Studies; Clinical Medicine; Enzyme-Linked Immunosorbent Assay; Epitopes - chemistry; Epitopes - immunology; Female; Follow-Up Studies; Humans; Hypertrophy; immune; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulin M - blood; Immunoglobulin M - immunology; Kardiologi; Kardiologi och kardiovaskulära sjukdomar; Klinisk medicin; Lipoproteins, LDL - chemistry; Lipoproteins, LDL - immunology; Male; Malondialdehyde - chemistry; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Molecular Sequence Data; Myocardial Infarction - epidemiology; Peptide Fragments - chemistry; Peptide Fragments - immunology; Peptide Library; peptide sequences; Prospective Studies; responses; Tunica Intima - pathology; Tunica Media - pathology; Ultrasonography; Autoimmunity; Human; apolipoproteins; Pathogenesis; peptide sequences; Cardiovascular disease; cardiovascular diseases; immune responses; Vascular disease; Apolipoprotein B; Lipoprotein LDL; Atherosclerosis; Oxidation
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/01.ATV.0000067935.02679.B0

OBJECTIVE—Atherosclerosis is associated with an immune response against oxidized LDL, which modulates the progression of the disease process. METHODS AND RESULTS—Using a library of polypeptides covering the complete sequence of apoB-100, the only major protein of LDL, we have identified over 100 different human antibodies reacting against aldehyde-modified apoB-100 sequences. IgM antibody titer levels decreased with age and were associated with the intima-media thickness of the carotid artery in subjects younger than 60 years. There were also inverse associations between IgM levels and oxidized LDL in plasma. In prospective clinical studies, antibody levels against several aldehyde-modified apoB-100 sites were associated with cardiovascular disease in this age group. Whether this immune response is adaptive (protective) or maladaptive (causal) in atherosclerosis requires further investigation. CONCLUSIONS—We have characterized a large number of epitopes within the apoB-100 component of oxidized LDL that provoke an immune response in humans. These findings will make it possible to study the role of immune responses against specific sites in oxidized LDL and to determine whether these immune responses influence the risk for future cardiac events.