Complexity of antigenic determinants and humoral responses in vascular injury

See article by Shinohara et al. [1] (pages 249–258) in this issue. Circulating antibodies, reacting with autoantigens in the vascular wall, are commonly harmless in healthy vessels but can turn pathogenic in the presence of vascular injury. The exact antigenic determinants and the role of such autoreactive antibodies remain unclear. In their present study appearing in this issue, Shinohara and coworkers [1] propose a xenogenic, vaccinal experimental approach in order to limit intimal proliferation in response to balloon-induced arterial wall injury in rabbits. Their observations suggest that the observed humoral response is responsible for the limitation of smooth muscle cell (SMC) migration and proliferation via an extracellular effect on the SMC response to growth factors and angiotensin II, as observed in vitro. While the involvement of autoreactive antibodies in human autoimmune diseases and their vascular targeting are beyond the scope of the present editorial, the observations of Shinohara and coworkers merit some comments. The authors [1] used a mixture of specific and non-specific cellular xenoantigens shared by cultured rat SMC rendered inert for immunization. They also used a homogenized rabbit SMC preparation, including membrane-exposed and intracellular antigens, for exploring the autoreactive determinants of the response. Therefore, a precise identification of the molecular targets of the humoral response is difficult to evaluate. The presence of auto-antibodies, within the intima in vivo, was … *Corresponding author. Email address: jbmichel{at}bichat.inserm.fr