HYPERACUTE REJECTIONS OF 2 CONSECUTIVE RENAL-ALLOGRAFTS AND EARLY LOSS OF THE 3RD TRANSPLANT CAUSED BY NON-HLA ANTIBODIES SPECIFIC FOR ENDOTHELIAL-CELLS

The immunological rejection of HLA-identical kidney transplants indica tes that non-HLA antigens may also be targets for transplant rejection . Interest in the possible role of endothelial specific antigens has g rown steadily over the years. Most of the studies published, regarding the association of such antibodies with rejection, have demonstrated the reactivity of endothelial antibodies also with monocytes and kerat inocytes, but not with lymphocytes. Such antibodies escape detection i n conventional crossmatch tests. In this paper, we present a case repo rt of a 10-year-old girl, whose two consecutive kidney allografts, (on e living and one cadaveric donor) were hyperacutely rejected in spite of the fact that she had neither been alloimmunized, nor had any HLA-s pecific antibodies. Endothelial cell specific antibodies were detected in vivo and in vitro after transplantation only 11 days apart, which were considered to be responsible for rejection. The third cadaveric k idney was lost within 1 week post-transplant. Immunopathological inves tigation of the three rejected grafts revealed deposition of IgM in th e endothelium of arteries and in some glomeruli. No deposition of IgG antibodies was found. Antibodies from this patient did not react with lymphocytes, monocytes or keratinocytes. Patient serum had IgM antibod ies that were specifically reactive with cultured endothelial cells, d emonstrated by binding in vitro and by complement-dependent cytotoxici ty of IL-P stimulated endothelial cells. No HLA antibodies were found following the first two transplantations, but were demonstrated 1 week after the third transplantation, at the time of an acute irreversible rejection. Western blots of proteins solubilized from endothelial cel l membranes, indicated that the antibodies reacted with a 97-110 kD pr otein. Endothelial cell antigen preparations were made from several di fferent umbilical cord veins. Some primary cell cultures, but not all, reacted with the patient's serum. Therefore, we suggest that the targ et determinant might be polymorphic. These findings imply that the non -HLA endothelial cell specific molecules may function as target(s) for hyperacute antibody-mediated destruction of kidney allografts.