Enzyme-linked immunosorbent assay spot detection of interferon-γ and interleukin 5-producing cells as a predictive marker for renal allograft failure

Background. Despite improvements in the shortterm survival of renal transplants, many allografts fail over the 5-10 years after transplantation. We sought to identify an immunologic assay that could identify those patients at high risk for future allograft failure, Methods. Blood samples were obtained from 23 renal allograft recipients with acute and/or chronic graft dysfunction and from 22 controls. Isolated peripheral blood lymphocytes (PBLs) were tested for interferon (IFN)-gamma and interleukin (IL)-5 production using an enzyme-linked immunosorbent spot assay. IFN-gamma:IL-5 ratios were calculated and compared between groups, Among the 23 patients with graft dysfunction, the ratios were also compared with graft function at 6 months. Results. IFN-gamma:IL-5 ratios of greater than or equal to 15 were associated with allograft rejection episodes in 8 of 12 cases, whereas 10 of 11 episodes of graft dysfunction from other causes (infection, drug toxicity, obstruction) were associated with values <15. All normal controls had values <15 (22/22). Among the graft recipients with acute renal failure, all patients with IFN-gamma:IL-5 ratios <15 exhibited improved renal function at 6-month follow-up (14/14), whereas 8 of 9 patients with IFN-gamma:IL-5 ratios greater than or equal to 15 developed allograft failure at 6 months (sensitivity 100%, specificity 93.3%), Conclusion. In renal transplant recipients with acute allograft dysfunction, mitogen-induced peripheral blood lymphocyte IFN-gamma:IL-5 ratios greater than or equal to 15 were highly predictive of allograft failure within 6 months of the assay. This test may be a useful prognostic marker for identification of transplant recipients with acute graft dysfunction who are at high risk for future graft loss and thus allow targeted therapeutic interventions to prolong graft survival.