Physiologic autoantibody and immunoglobulin interventions during aging.

Physiologic autoantibodies, that is, those with an active physiologic role, are an important part of the normal human immune system and are essential in maintaining homeostasis. Evidence suggests that the body uses autoantibodies to prevent disease and to self-treat diseases once started. This suggests a potential therapeutic role for autoantibodies, or, even better, a way to use them to prevent disease. Their capacity to remove aged, damaged cells is well established. Immunoglobulin (Ig) G autoantibodies bind to senescent cell antigen (SCA), which is an altered band 3 anion exchanger protein found mainly on aged cells. Once bound, IgG triggers the removal of the senescent cells by macrophages. Band 3 is altered primarily by oxidation, which in turn generates SCA. These studies demonstrated that oxidation can generate neoantigens that the immune system will recognize. Band 3 isoforms are ubiquitous: they have been found in all mammalian cells and species so far examined. The innate immune response to band 3 membrane proteins, and their regulation of cellular lifespan and therapeutic potential will be presented. Examples of other potential innate and physiologic autoantibodies include neuroprotective antibodies to amyloidgenic toxic peptides and antibodies to oxidized LDL (OxLDL), which modify the natural progression of atherosclerosis.