Lymphatic CD68+ Endothelial Cells in Cardiac Allograft Humoral Rejection

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Purpose To evaluate possible implication of lymphatic capillary endothelium in cardiac allograft rejection, and its significance for antibody-mediated rejection (AMR) diagnostics. Methods and Materials Endomyocardial biopsies were taken from fifty patients over a period of 1 week to 15 years after transplantation. For immunohistochemistry, frozen sections were treated with anti-IgG and anti-IgM antibodies (Dako) and by antibodies against the C4d component of complement (Quidel). Only biopsy specimens that did not show any signs of cell-mediated rejection were analyzed. AMR was diagnosed based on deposition of fixated IgG (and/or IgM) and C4d in the blood vessel wall, and on clinical picture or presence of macrophages in blood vessels. Lysosome-containing CD68-positive cells were detected using monoclonal antibody to CD68 (clone KP1, Dako). Sections of the myocardium from patients with ischemic and dilated cardiomyopathies obtained after transplantation were used as controls. Results In allografts that displayed no humoral rejection features, such as fixation of immune complexes or C4d, only few (5-10) of the CD68+ cells were detected in the interstitial regions of the myocardium. However, when either of the humoral rejection traits were observed, numerous CD68+ cells were revealed in the allograft myocardium and endocardium. Along with round CD68+ cells (macrophages), we observed a significant number of elongated CD68+ cells representing, most likely, lymphatic capillaries, as there are no blood vessels in the endocardium. Overall, in our experience, the presence of more than thirty CD68+ cells in the field of view with 40x objective, may be considered as one of the indicators of humoral rejection. Conclusions The observed activation of the lymphatic capillary endothelial cells suggests that they play an important homeostatic role by scavenging circulating and tissue-fixed immune complexes elicited by the humoral rejection of the allotransplant and thus may be regarded as a part of the “mononuclear phagocyte” system.