Pretransplant low CD3+CD25high cell counts or a low CD3+CD25high/CD3+HLA-DR+ ratio are associated with an increased risk to acute renal allograft rejection.

Background: Detection of markers predicting allograft rejection is important for risk assessment before kidney transplantation, as well as to minimize posttransplantation immunosuppression.

Methods: We studied the expression of CD25, HLA-DR, CD134, CD62L, and CD44 by flow cytometry in CD4, CD8, and CD3 cells, from pretransplant blood samples from 91 transplanted patients accounting for 16 episodes of acute renal rejection in the first month after transplantation.

Results: None of the activation markers showed a significant association to acute rejection. Early rejectors showed less pretransplant CD3CD25 cells than nonrejectors (0.79%±0.50% vs. 1.51%±0.79% of CD3 cells; P=0.001) and a lower CD3CD25/CD3HLA-DR ratio (0.043±0.034 vs. 0.111±0.079; P<0.00001). When levels of CD25 cells fell below 0.7% of CD3 cells, the odds ratio of suffering an episode of acute rejection was 105 fold (95% confidence interval: 11.41-966.43, P<0.0001), with a sensitivity (true-positive results) of 0.63 and a specificity (true-negative results) of 0.98 for predicting the risk of acute rejection. Furthermore, when the CD3CD25/CD3HLA-DR ratio fell below 0.04, the odds ratio of suffering an episode of acute rejection was 7.71 fold (95% confidence interval: 2.29-25.97, P=0.001), with a sensitivity of 0.56 and a specificity of 0.86 for predicting risk of acute rejection.

Conclusions: Our results suggest that low pretransplant levels of CD3CD25 cells or a low CD3CD25/CD3HLA-DR ratio could identify those patients with an increased risk of early acute allograft rejection. If these data can be independently confirmed, pretransplant CD3CD25 cells and the CD3CD25/CD3HLA-DR ratio might provide additional information for risk assessment before kidney transplantation.