Antibodies to cholesterol, cholesterol conjugates and liposomes: implications for atherosclerosis and autoimmunity

Polyclonal and monoclonal antibodies to cholesterol are readily induced by injecting cholesterol-loaded liposomes containing lipid A as an adjuvant. Analysis of the literature reveals that conjugates of cholesterol, and conjugates of analogues of cholesterol, with heterologous proteins or lipids have been used as antigens in various studies since 1925, and this has led to successful development of immunoassays for steroid hormones. It is concluded that cholesterol is a highly immunogenic molecule. The ability of monoclonal antibodies to cholesterol to react with liposomes containing cholesterol to cause complement-dependent immune damage to the liposomes is strongly influenced by the lipid composition of the liposomes, the amount of cholesterol in the liposomes, and the reaction temperature. The antibodies also react with crystalline cholesterol in a solid-phase ELISA and, depending on the particular monoclonal antibody, immune reactivity may or may not be observed with cholesterol esters, cholesterol analogues, or steroid hormones. Analysis by ELISA has revealed that virtually all normal human sera contain varying levels of naturally occurring IgG and IgM autoantibodies to cholesterol. Naturally occurring autoantibodies to cholesterol are also observed in pigs, but not in guinea pigs. Possible implications of these investigations for theories of immune mechanisms that may have beneficial or detrimental roles in processes of aging, atherosclerosis, and vascular diseases are discussed.