Cardiac allograft vasculopathy - IgM antibody responses to donor-specific vascular endothelium

We have previously demonstrated that heightened cell-mediated immunity to donor-specific endothelium was associated with an increased incidence of cardiac allograft vasculopathy (CAV) at 1 year postcardiac transplantation. We further demonstrated that the development of IgG antibody directed to donor-specific HLA antigens was extremely uncommon and, furthermore, had no relationship to the development of CAV. Subsequent studies have demonstrated a correlation between IgM antibody directed against endothelial cell antigens and the development of CAV. Accordingly, recipient serum obtained between 6 and 8 weeks (early) and 1 year (late) after transplantation were reacted with recombinant human interferon (rhIFN)-gamma pretreated donor-specific human aortic endothelial cells (HAECs) in 10 recipients with and 10 recipients without CAV at 1 year after transplantation. HAEC IgM binding was assessed by flow cytometry and complement fixation and HAEC lysis was measured using standard chromium release assays. Seven of 10 and 5 of 10 patients with CAV had IgM detected by flow at early and late time points, respectively (14+/-2 and 16+/-5 mean channel shift), whereas 5 of 10 and 6 of 10 patients without CAV had IgM detected by flow at early and late time points, respectively (15+/-4 and 14+/-3 mean channel shift). This finding was not different between groups. Despite between 50% and 70% of all patients having detectable IgM binding to ECs, no patient's serum was cytotoxic to its donor-specific HAECs. We conclude that IgM antibody to endothelial cells is common (at low titers) after transplantation. This antibody is not cytotoxic and in this study provided no discrimination between those with and without chronic rejection.