Antibody-mediated graft versus host reactions in renal transplantation

Abstract

Graft versus host reactions (GvHR) are frequent and severe complications of bone marrow transplantation. Although the major symptoms of GvHR in these patients are thought to be mediated through T lymphocytes, both clinical and experimental observations indicate that antibody production also is stimulated by GvHR. In animal models of GvHR, Gleichmann and colleagues 1 have demonstrated a range of antibody-mediated lesions, which become more pronounced when the antigenic differences between donor and host favor stimulation of helper T lymphocytes and a chronic disease process. Cnly limited attention has been given to the possibility that 'passenger lymphocytes' in solid tissue transplants may cause GvHR. In 1953 Simonsen suggested that the plasma cells he observed in the interstitium of transplanted canine kidneys were possibly of donor origin, but he abandoned this hypothesis when radiolabelling experiments demonstrated that cells of host origin infiltrated skin and kidney allografts (reviewed in Ref. 2). Yet, sporadic cases have been reported of unexpected hemolytic episodes following the transplantation of kidney, liver or lung from a donor who is Rh negative or O blood group to a patient whose erythrocytes bear Rh, A, B0 or AB antigens 3-1°. One report suggested that irradiation of the donor kidney prevented antibody production to the recipient's erythrocytes 5, and in a few cases antibodies that were eluted from the recipients' erythrocytes have been shown to be of donor a!!otype9-11; thus substantiating the hypothesis that the hemolytic episodes reflect GvHR. Some investigators 5.6.11 have argued that this phenomenon may be more frequently encountered when cyclosporine A (CyA) is used as an immunosuppressive agent, because selective effects of CyA on T lymphocytes might prevent rejection of the donor Blymphocytes but not suppress antibody production by these lymphocytes. Several recent reports have documented the Ionyitudinal titers of circulating antibodies to recipient ~, B or Rh antigens in CyA treated renal transplant recipients. These antibodies have been detected within 1 to 3 weeks after transplantation and they can persist for months 6, even after immunosuppression is discontinued 8. Both IgG and IgM antibodies have been detected in the serum and in eluates from the recipients' erythrocytes by the indirect antiglobulin test