Apolipoprotein B100 autoimmunity and atherosclerosis - disease mechanisms and therapeutic potential.
OBJECTIVE
Adaptive immune responses have been shown to play an important role in the atherosclerotic disease process and both pathogenic and protective immunity has been identified. Apolipoprotein (apo) B100 appears to be a key antigen and novel therapies modulating immune responses against apo B100 have shown promising results in experimental models. This review will discuss recent developments in the mechanistic understanding of apo B100 autoimmunity and approaches taken to use this knowledge for development of novel therapies.


RESULTS
It has recently been shown that not only apo B100 modified by oxidation but also nonmodified apo B100 is targeted by autoimmune responses. This implies that a corresponding set of regulatory T cells with the same antigen specificity must exist and that these cells under normal circumstances are able to prevent autoimmunity against LDL. Recent studies also suggest that the atheroprotective effect of apo B100 peptide immunization acts by re-enforcing the activity of such cells.


CONCLUSIONS
These novel findings suggest that aggravation of plaque inflammation may occur as a result of a local loss of tolerance against LDL in the plaque due to insufficient activity of regulatory T cells. Restoration of lost tolerance represents an interesting novel approach for treatment of cardiovascular disease.
Department of Clinical Sciences Malmö, Skåne University Hospital, Lund University, Sweden. jan.nilsson@med.lu.se
Jan
J
Nilsson
Harry
H
Björkbacka
Gunilla Nordin
GN
Fredrikson
D000818:Animals; D053299:Apolipoprotein B-100 / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D015551:Autoimmunity; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D008077:Lipoproteins, LDL / Q000276:immunology; D008213:Lymphocyte Activation; D010084:Oxidation-Reduction; D058226:Plaque, Atherosclerotic / Q000276:immunology / Q000473:pathology / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D053299:Apolipoprotein B-100; D000939:Epitopes; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein