Anti-cell surface endothelial antibodies in sera from cardiac and kidney transplant recipients: Association with chronic rejection

The aetiologies of accelerated or transplant-associated coronary artery disease (TxCAD) following cardiac transplantation and chronic rejection following renal transplantation remain ill-defined. Previous studies have used Western blotting to demonstrate an association between the formation of anti-endothelial (anti-EC) antibodies and TxCAD after heart transplantation. However, Western blotting favours detection of cytosolic proteins. The objectives of this study were to determine whether flow cytometry, a method which detects antigens on the cell surface, could be used to detect anti-EC antibodies and also whether the observations would extend to renal transplant patients with chronic rejection. Flow cytometry was used to look for antibodies reactive with the surface antigens of macrovascular and microvascular endothelial cell lines in sera from 44 cardiac and 35 renal transplant recipients before and after transplantation. In addition, sera from normals (n = 20), patients with nontransplant CAD (n = 50) and patients with unrelated diseases (n = 40) were investigated. Of 23 cardiac recipients who had developed TxCAD at one or two years post-transplant, 61% had IgM and 13% had IgG anti-EC antibodies posttransplantation. In contrast, in 21 cardiac recipients who had not developed TxCAD 14% had IgM and 14% IgG anti-EC antibodies. There was little evidence for the presence of anti-EC antibodies in cardiac recipients before transplantation. Of 26 renal transplant recipients whose transplants failed due to chronic rejection, 42% had IgG and 19% IgM anti-EC antibodies post-transplantation. Of nine renal recipients whose grafts were either functioning normally or who had acutely rejected, none had IgG or IgM anti-EC antibodies either pre- or posttransplantation. The anti-EC antibodies were not found in normals and were rare (less than 4%) in the other disease groups; they do not appear to be autoantibodies. In conclusion, these results suggest the FAGS assay could be an informative and rapid test to provide more information on chronic rejection following cardiac and renal transplantation.