Transplant rejection associatd with the presence of human leucocyte antigen antibodies detected by the FcγR inhibition test but not by the lymphocytotoxicity test

The unselected sera from 869 human leucocyte antigen (HLA) immunized patients awaiting a kidney transplant were analysed using the complement-dependent lymphocytotoxicity test (LCT) with peripheral mononuclear blood cells and the complement-independent immune phagocytosis inhibition test (IPI) with monocytes derived from between five and 10 donors. Sera from 659 patients were LCT and IPI negative when tested against this small panel. Seventy-nine patients had HLA immunoglobulin-G (IgG) antibodies, detectable by the IPI only. Sera from 117 patients had concordantly positive IPI and LCT reactivity with cells from certain donors and concordantly negative IPI and LCT reactivity with cells from other donors (no isolated IPI and no isolated LCT reactions). Fourteen patients had a mixed type of reactivity. Laboratory findings were interpreted along with the transplantation history of the respective patients. Group 1 comprised patients for whom negative results were obtained in both the LCT and the IPI; group 2 patients who were also LCT negative but IPI positive. These two groups showed a significantly different history with respect to the number of irreversible immunological transplant rejections. In group 1, 25.3% of the transplanted kidneys had been rejected whereas in group 2, 56.0% of the kidneys had been rejected (p = 5 x 10(-5)). The high incidence of rejections in the group showing only IPI reactions was comparable with that of group 4 comprising patients with concordant IPI and LCT reactions (59.4%). It is inferred from this retrospective study that renal allograft rejection is associated with the development of IPI reactive antibodies which are not detectable by the LCT. The presence of these antibodies prior to transplantation could be detrimental to the transplanted organ. This being the case, the incidence of transplant failures could be reduced by pretransplant screening using the IPI and by avoiding crossmatch positive donors identified by IPI, especially in patients waiting for a retransplantation.