Title | Urinary cell levels of mRNA for OX40, OX40L, PD-1, PD-L1, or PD-L2 and acute rejection of human renal allografts. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Afaneh C, Muthukumar T, Lubetzky M, Ding R, Snopkowski C, Sharma VK, Seshan S, Dadhania D, Schwartz JE, Suthanthiran M |
Journal | Transplantation |
Volume | 90 |
Issue | 12 |
Pagination | 1381-7 |
Date Published | 2010 Dec 27 |
ISSN | 1534-6080 |
Keywords | Acute Disease, Adult, Antigens, CD, Antigens, Differentiation, B7-H1 Antigen, Continental Population Groups, Creatinine, Female, Graft Rejection, Humans, Intercellular Signaling Peptides and Proteins, Kidney Transplantation, Male, Middle Aged, OX40 Ligand, Predictive Value of Tests, Programmed Cell Death 1 Ligand 2 Protein, RNA, Messenger, ROC Curve, Transplantation, Homologous |
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. |
DOI | 10.1097/TP.0b013e3181ffbadd |
Alternate Journal | Transplantation |
PubMed ID | 21079547 |
PubMed Central ID | PMC3033230 |
Grant List | R37 AI051652 / AI / NIAID NIH HHS / United States T32 HL08382401 / HL / NHLBI NIH HHS / United States UL1 RR024996 / RR / NCRR NIH HHS / United States ULI RR 024996 / RR / NCRR NIH HHS / United States R37 AI051652-08 / AI / NIAID NIH HHS / United States |
Related Faculty:
Surya V. Seshan, M.D.