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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:872.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Gunilla Nordin Fredrikson; Bo Hedblad; Göran Berglund; Ragnar Alm; Mikko Ares; Bojan Cercek; Kuang-Yuh Chyu; Prediman K. Shah; Jan Nilsson

From the Departments of Medicine (G.N.F., B.H., G.B., R.A., M.A., J.N.) and Community Medicine (B.H.), Malmö University Hospital, Lund University, Sweden; Department of Biomedical Laboratory Science (G.N.F.), Malmö University, Sweden; and Atherosclerosis Research Center (B.C., K.-Y.C., P.K.S.), Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, Calif.

Correspondence to Gunilla Nordin Fredrikson, Wallenberg Laboratory, 1st Floor, Malmö University Hospital, S-205 02 Malmö, Sweden. E-mail Gunilla.Nordin_Fredrikson{at}medforsk.mas.lu.se

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.

Key Words: apolipoproteins • atherosclerosis • cardiovascular diseases • immune responses • peptide sequences

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