Lipoprotein Autoantibodies (original) (raw)

2003, Clinical and Vaccine Immunology

Two decades ago, well before the inflammatory nature of arteriosclerosis was generally accepted, several groups reported the finding of immunoglobulins and various complement components in atheromatous plaques of humans and rabbits (12, 42, 69). A decade later apolipoprotein B (ApoB) extracted from atheromatous lesions was found to react with monoclonal antibodies against malondialdehyde (MDA)-and 4-hydroxynonenal (HNE)-lysine, two common modifications of oxidized low-density lipoprotein (oxLDL) (38, 73), and immunoglobulin G (IgG) isolated from rabbit and human atherosclerotic lesions showed reactivity with MDA-and coppermodified LDL (74). These seminal observations represent arguably the best evidence available for the involvement of modified LDL antibodies and in situ formed antigen-antibody complexes in the induction and/or perpetuation of chronic vascular inflammation. It also gave a solid rationale for expanding study of the immunogenic properties of modified forms of LDL and to the development of methods for their assay in serum. From the immunological point of view, oxLDL has been studied in most detail. LDL oxidation affects both the lipid and protein components of LDL. Reactive aldehyde products result from the oxidation of polyunsaturated fatty acids and include MDA and 4-HNE, capable of attaching covalently to the ε-amino groups of lysine residues of ApoB (49, 50, 73). These modifications are present in copper-oxidized LDL, which was found to have structural and functional properties similar to those of LDL isolated from atherosclerotic plaques (73) and to react with monoclonal antibodies produced in guinea pigs against MDA and HNE-lysine (38, 73). Detailed investigations have also been carried out with advanced glycosylation end product-modified LDL (AGE-LDL). Advanced glycosylation involves a chain of chemical reactions that starts with the nonenzymatic addition of reducing sugars to protein amino groups (Schiff base, Amadori adducts). If the half-life of a protein is sufficiently long, additional reactions take place leading to the formation of a heterogeneous family of sugar-amino acid adducts collectively known as "advanced glycosylation end products" (AGE) (43). LDL, like most plasma proteins, is susceptible to AGE modification (45). AGE-modified proteins are immunogenic (18), a property that