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

Cheguevara Afaneh, Thangamani Muthukumar, Michelle Lubetzky, Ruchuang Ding, Catherine Snopkowski, Vijay K. Sharma, Surya Seshan, Darshana Dadhania, Joseph E. Schwartz, Manikkam Suthanthiran

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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.

Original languageEnglish
Pages (from-to)1381-1387
Number of pages7
JournalTransplantation
Volume90
Issue number12
DOIs
Publication statusPublished - 27 Dec 2010

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Keywords

  • Acute rejection
  • Costimulation
  • OX40
  • Urinary biomarkers

ASJC Scopus subject areas

  • Transplantation

Cite this

Afaneh, C., Muthukumar, T., Lubetzky, M., Ding, R., Snopkowski, C., Sharma, V. K., Seshan, S., Dadhania, D., Schwartz, J. E., & Suthanthiran, M. (2010). Urinary cell levels of mRNA for OX40, OX40L, PD-1, PD-L1, or PD-L2 and acute rejection of human renal allografts. Transplantation, 90(12), 1381-1387. https://doi.org/10.1097/TP.0b013e3181ffbadd