Vascular events in placentae and organ allografts

This investigation explores the transplantation analogy of placentae with allografted human organs. Biopsies of cardiac and renal allografts and placentae were studied immunocytochemically with antibodies to components of the immunological, coagulational, anticoagulational, and fibrinolytic systems. Cellular rejection of cardiac and renal allografts was identified by infiltrating lymphocytes and macrophages. This was accompanied by vascular damage characterized by loss of endothelial anticoagulant pathways, vascular deposits of fibrin, and depletion of arterial tissue plasminogen activator (tPA). Failing allografts, including placentae from abnormal pregnancies, demonstrated coagulation/fibrinolytic changes consistent with vascular rejection, regardless of the presence of cellular infiltrates. An IgM autoantibody to allogeneic endothelium was associated with vascular protection. Its presence in cardiac and renal transplant biopsies was associated with an absence of fibrin deposits, and its absence was associated with vascular damage. Atherosclerosis commonly was identified in allograft biopsies (including placentae from abnormal pregnancies). These changes were shown in serial biopsies of transplanted hearts to be preceded by or associated with diminished IgM autoantibody, impaired endothelial anticoagulant pathways, vascular fibrin deposits, and depleted arterial reactivity for tPA. These results indicate the transplantation analogy of pregnancy should be viewed more specifically as vascular smooth muscle cell and endothelial responses to as yet unidentified microenvironmental stimuli.