Urinary cell levels of mRNA for OX40, OX40L, PD-1, PD-L1, or PD-L2 and acute rejection of human renal allografts

C Afaneh, T Muthukumar, M Lubetzky, R Ding… - …, 2010 - journals.lww.com
C Afaneh, T Muthukumar, M Lubetzky, R Ding, C Snopkowski, VK Sharma, S Seshan…
Transplantation, 2010journals.lww.com
Background. The positive costimulatory proteins OX40 and OX40L and negative regulatory
proteins programmed death (PD)-1, PD ligand 1, and PD ligand 2 have emerged as
significant regulators of acute rejection in experimental transplantation models. Methods. We
obtained 21 urine specimens from 21 renal allograft recipients with graft dysfunction and
biopsy-confirmed acute rejection and 25 specimens from 25 recipients with stable graft
function and normal biopsy results (stable). Urinary cell levels of mRNAs were measured …
Abstract
Background.
The positive costimulatory proteins OX40 and OX40L and negative regulatory proteins programmed death (PD)-1, PD ligand 1, and PD ligand 2 have emerged as significant regulators of acute rejection in experimental transplantation models.
Methods.
We obtained 21 urine specimens from 21 renal allograft recipients with graft dysfunction and biopsy-confirmed acute rejection and 25 specimens from 25 recipients with stable graft function and normal biopsy results (stable). Urinary cell levels of mRNAs were measured using real-time quantitative polymerase chain reaction assays, and the levels were correlated with allograft status and outcomes.
Results.
Levels of OX40 mRNA (P< 0.0001, Mann-Whitney test), OX40L mRNA (P= 0.0004), and PD-1 mRNA (P= 0.004), but not the mRNA levels of PD ligand 1 (P= 0.08) or PD ligand 2 (P= 0.20), were significantly higher in the urinary cells from the acute rejection group than the stable group. Receiver operating characteristic curve analysis demonstrated that acute rejection is predicted with a sensitivity of 95% and a specificity of 92%(area under the curve= 0.98, 95% confidence interval 0.96–1.0, P< 0.0001) using a combination of levels of mRNA for OX40, OX40L, PD-1, and levels of mRNA for the previously identified biomarker Foxp3. Within the acute rejection group, levels of mRNA for OX40 (P= 0.0002), OX40L (P= 0.0004), and Foxp3 (P= 0.04) predicted acute rejection reversal, whereas only OX40 mRNA levels (P= 0.04) predicted graft loss after acute rejection.
Conclusion.
A linear combination of urinary cell levels of mRNA for OX40, OX40L, PD-1, and Foxp3 was a strong predictor of acute rejection in human renal allograft biopsies. This prediction model should be validated using an independent cohort of renal allograft recipients.
Lippincott Williams & Wilkins