High Pre-Transplant Serum Levels of CXCL10 Predict Early Renal Allograft Failure

Background: The chemokine CXCL10 is a potent chemoattractant for activated lymphocytes and dendritic cells and mediates vascular injury by inducing intimal hyperplasia and inhibition of endothelial cell growth. Neutralisation of CXCL10 prolongs allograft survival and transplant knock-out models have shown that this chemokine is required for the initiation and development of graft failure due to both acute and chronic rejection. In the present study, we investigated whether pre-transplant CXCL10 serum levels may predict the recipient risk of graft rejection and transplant failure. Methods: Pre-transplant sera of 299 cadaver kidney graft recipients were tested retrospectively for serum CXCL10 levels by a quantitative sandwich immunoassay. Results: Kidney graft recipients with normally functioning grafts showed higher pre-transplant CXCL10 serum levels than healthy controls, but significantly lower than patients who experienced graft failure (133.47±119.6 vs. 182.8±155.01 pg/ml; p<0.05). After the assignment of all patients to four groups at 25°, 50° and 75° centiles according to serum CXCL10 levels, the censored survival rates of grafts were 97.3%, 94%, 93.3%, 85.3% at 1-year. Accordingly, patients with the highest pre-transplant serum CXCL10 levels (75°-100°) centiles showed an increased frequency and severity of rejection episodes in the first month after transplantation. Conclusions: The results of this study show that high pretransplant serum CXCL10 levels represent an important predictive risk factor for the development of rejection and transplant failure, thus suggesting that measurement of pre-transplant serum CXCL10 levels might represent a clinically useful marker for the transplant outcome.