Vascular immunopathology and atheroma development in human allografted organs

Human atherosclerosis requires decades to develop spontaneously, and its development customarily is not monitored by serial biopsies. Atherosclerosis in allografts develops within months, and biopsy specimens are usually obtained from the grafts. We have used immunocytochemical techniques to study biopsy specimens of cardiac and renal allografts for parameters of vascular changes. The antibodies used in this investigation were specific for T lymphocytes, macrophages, IgM, and complement, and detailed studies were done with the use of antibodies specific for components of the hemostatic, fibrinolytic, and natural anticoagulant pathways. The results indicated a lack of association between the appearance of cellular infiltrates and measurable alterations in vascular endothelium and smooth-muscle cells. Although infiltrating macrophages and lymphocytes were identified in biopsy specimens with vascular change, such changes were also observed in biopsy specimens that were devoid of cellular infiltrates. The most prominent vascular changes in endothelium and smooth-muscle cells were accelerated hemostasis, depressed fibrinolysis, and deranged anticoagulant pathways. A negative association between the presence of IgM and fibrin on endothelial cells was also identified. Whether vascular changes are due to immunologically mediated reactions or to as yet undefined metabolic stresses of the graft-host relationship remains to be determined. This study provides a model for the study of vascular changes in atheroma development as viewed through the window of transplant-induced atherosclerosis.