Effect of Antiidiotypic Antibodies to HLA on Graft Survival in Renal-Allograft Recipients

Although the presence in the recipient of preformed antibodies to HLA antigens in the kidney of a renal-transplant donor may be associated with early graft failure, such grafts are often well tolerated. We have investigated the possibility that anti-anti-HLA (antiidiotypic) antibodies influence the outcome of renal transplantation in recipients with a history of presensitization to their donor's HLA antigens. A retrospective analysis of 20 such cases showed that in 10 patients the transplanted kidney was rejected within one month, whereas in the remaining 10 the graft was tolerated for more than a year. Nine of the 10 patients in whom the graft was tolerated had anti-anti-HLA antibodies at the time of transplantation. Nine of the 10 patients in whom the graft was rejected had antibodies that potentiated, rather than blocked, the cytotoxic activity of anti-donor-HLA antibodies. These results suggest that patients with anti-anti-HLA antibodies specific for a potential donor can safely undergo transplantation, despite a prior history of anti-HLA antibodies. At the time of transplantation, patients who have antibodies that potentiate the cytotoxic activity of a historically positive serum are at high risk of graft rejection within a short period. Taking these considerations into account may improve the reliability of cross-matching in renal transplantation. (N Engl J Med 1987; 316:1450–5.), THERE are now 10,000 patients with end-stage renal disease who are awaiting transplantation in the United States. Cadaveric grafts should eventually be available for about 50 percent of this population. In spite of an increased rate of successful transplantation after cyclosporine-based immunosuppressive therapy, early failures still occur in as many as 20 percent of recipients of renal allografts.^1,2 To a large extent such failures are determined by immunologic factors, since most patients with graft rejection have a history of immunization to HLA antigens.³ Forty-five percent of the patients with early rejection of primary grafts become sensitized to HLA antigens and…