title: Autoimmune responses against the apo B-100 LDL receptor-binding site protect against arterial accumulation of lipids in LDL receptor deficient mice.
abstract: BACKGROUND
  Oxidation of LDL is associated with generation of autoantibodies against a large number of different aldehyde-modified peptide sequences in apo B-100. Autoantibodies recognizing peptide sequences in the LDL receptor-binding region of apo B-100 could potentially affect both cholesterol metabolism and atherosclerosis. The aim of the present study was to determine physiological effects of induction of immune responses against the apo B-100 LDL receptor-binding site in mice deficient for the LDL receptor.
  
  
  RESULTS
  Mice received three immunizations, beginning at 6 weeks of age, with aldehyde-modified or non-modified peptides corresponding to the amino acid sequence of the LDL receptor-binding site. Analysis of antibody response by ELISA unexpectedly revealed high titers of pre-existing IgG against both native and aldehyde-modified binding site sequences in non-immunized mice. Immunization with aldehyde-modified binding site sequences resulted in an almost complete down-regulation of this autoimmune response. It was also associated with a rapid increase in lipid-rich plaques in the aorta and a substantial depletion of the lipid content of the liver, whereas plasma lipid and apo B values were similar in all groups.
  
  
  CONCLUSIONS
  These observations demonstrate existence of an endogenous T cell-dependent autoimmune response against the LDL receptor-binding site in LDL receptor(-/-) mice and suggest that this may help to prevent accumulation of lipoprotein lipids in the artery wall, whereas immunization with the corresponding aldehyde modified sequence down-regulates this response and induces substantial atherosclerotic development.
authors: Department of Biomedical Laboratory Science, Malmö University Hospital, Lund University, S-205 02 Malmö, Sweden. gunilla.nordin_fredrikson@med.lu.se
authors: Gunilla Nordin
authors: GN
authors: Fredrikson
authors: Marie W
authors: MW
authors: Lindholm
authors: Irena
authors: I
authors: Ljungcrantz
authors: Ingrid
authors: I
authors: Söderberg
authors: Prediman K
authors: PK
authors: Shah
authors: Jan
authors: J
authors: Nilsson
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology; D053299:Apolipoprotein B-100 / Q000378:metabolism*; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015551:Autoimmunity; D001665:Binding Sites / Q000276:immunology; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011973:Receptors, LDL / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism
chemical_list: D000447:Aldehydes; D053299:Apolipoprotein B-100; D008055:Lipids; D010446:Peptide Fragments; D011973:Receptors, LDL; D000685:Serum Amyloid A Protein