Atheroarteritis: a combined immunological and lipid imbalance

This report traces the development of our knowledge about immune-complex arteritis from the early 20th Century to the present time. The emphasis is on the work which began with the seminal observations of serum sickness by Longcope, MacKenzie, and Rich, to the pathogenetic studies of serum sickness arteritis in rabbits by several groups including the outstanding contributions by Dixon and coworkers concerning the role of circulating immune complexes. This work was followed by investigations of the relationship to atherosclerosis revealed by the sustained studies by Minick et al. on serum sickness arteritis in hypercholesterolemic rabbits. This pioneering research work has more recently been of pivotal value in understanding the arteritis observed in certain primate species such as the cynomolgus and the nemestrina, in human lupus erythematosus, and in organ transplantation arteritis. More recently it has become apparent that one of the microscopic hallmarks of this type of immune complex injury is the concentic micro-architecture of the inflammatory arterial lesions, for which, when they are also lipid containing, we have coined the term artheroarteritis. The contributions of the neoantigens from glycosylated LDL and oxidized LDL to the development of this type of atheroarteritis are considered. New frontiers in this area of research are being opened by the PDAY study which offers new opportunities to link circulating immune complexes and new antigens to arheroarteritis with its accelerated stenotic arterial lesion development.