Role of antibodies in rejection

Abstract

Recent evidence suggests that antibody plays a role in the pathogenesis of both acute rejection and accelerated coronary artery disease following human cardiac transplantation. There is strong evidence that posttransplant monitoring identifies patients at risk of developing transplant-associated coronary artery disease. That antibody is either essential for or influences the nature of the vascular lesion is supported by experimental models of cardiac graft vasculopathy. One of the major concerns in this area is that the specificities of antibodies (formed in patients) remain poorly defined. Major histocompatibility and non–major histocompatibility target antigens have been described. Traditionally, cytotoxic antibodies have been detected, but newer methods of detecting noncytotoxic antibodies and use of endothelial cells as targets should expand and clarify the range of antibodies being produced. The mechanism whereby antibody causes vascular lesions is not understood but almost certainly involves activation of donor endothelial cells. Indirect presentation of graft antigens (including non-HLA or minor antigens) and epitope spreading drive chronic rejection; such an expansion of the immune response probably includes antibody production against many different HLA and non-HLA antigens.