title: Apolipoprotein B-100 Antibody Interaction With Atherosclerotic Plaque Inflammation and Repair Processes.
abstract: OBJECTIVE
  Treatment with IgG against the malondialdehyde (MDA)-modified apolipoprotein B-100 epitope p45 reduces atherosclerosis in experimental models. This study investigated the association between p45 IgG autoantibodies and plaque inflammation in subjects with advanced cardiovascular disease.
  
  
  METHODS
  Native and MDA-p45 IgG levels were analyzed by ELISA in 349 carotid endarterectomy patients. In a subcohort of 195 subjects, endarterectomy samples were analyzed by immunohistochemistry and ELISA to determine plaque constituents and inflammation. Peripheral blood mononuclear cells were isolated from healthy donors.
  
  
  RESULTS
  Patients with preoperative events of neurological ischemia had lower levels of native p45 IgG. Low levels of MDA-p45 IgG were associated with increased risk of postoperative cardiovascular death during a mean follow-up of 54 months. High plasma levels of native p45 IgG were associated with increased plaque content of collagen and smooth muscle cell growth factors, as well as with lower levels of proinflammatory cytokines. Exposure of peripheral blood mononuclear cells from healthy donors to recombinant MDA-p45 IgG in presence of oxidized low-density lipoprotein reduced the expression of tumor necrosis factor-α and stimulated release of smooth muscle cell growth factors.
  
  
  CONCLUSIONS
  This study confirms previous experimental findings of anti-inflammatory properties of apolipoprotein B-100 p45 antibodies and provides the first clinical evidence of associations between p45 IgG autoantibody levels and atherosclerotic plaque inflammation, plaque repair as well as prevalent and incident cardiovascular events in carotid endarterectomy patients. These findings suggest the possibility that treatment with anti-p45 antibodies may have beneficial effects in advanced cardiovascular disease.
authors.affiliation: From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Asciutto
authors.affiliation: From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Wigren
authors.affiliation: From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Gunilla Nordin
authors.initials: GN
authors.lastname: Fredrikson
authors.affiliation: From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Ingrid Yao
authors.initials: IY
authors.lastname: Mattisson
authors.affiliation: From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Caitriona
authors.initials: C
authors.lastname: Grönberg
authors.affiliation: From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Ragnar
authors.initials: R
authors.lastname: Alm
authors.affiliation: From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Harry
authors.initials: H
authors.lastname: Björkbacka
authors.affiliation: From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Nuno V
authors.initials: NV
authors.lastname: Dias
authors.affiliation: From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Edsfeldt
authors.affiliation: From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonçalves
authors.affiliation: From the Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden. jan.nilsson@med.lu.se.
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053299:Apolipoprotein B-100 / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012307:Risk Factors
chemical_list: D053299:Apolipoprotein B-100; D001323:Autoantibodies; D016207:Cytokines; D008077:Lipoproteins, LDL
keywords: antibodies; atherosclerosis; collagen; inflammation; malondialdehyde