#16-OR
FoxP3+ REGULATORY CELLS IN URINE: A BIOMARKER OF RENAL ALLOGRAFT REJECTION OUTCOME.
D. Dadhania MD 1,2, T. Muthukumar MD 1, R. Naqvi MD 1, C. Snopkowski BS 1, R. Ding MD 1, V. Sharma PhD 1,2, B. Li PhD 1, S. Seshan MD 1 and M. Suthanthiran MD 1,2. 1 Nephrology & Transplantation Medicine, Cornell University, NY, NY, USA and 2 Rogosin Institute, NY, NY, USA .
Recent studies indicate that regulatory T cells expressing transcription factor FoxP3 are important in regulating autoimmunity and the development of tolerance. Herein, we investigated the hypothesis Foxp3+ regulatory cells determine the outcome of acute rejection of renal allografts.
Urinary cell mRNA profiles of 36 renal allograft recipients with biopsy proven acute renal allograft rejection were determined with the use of real time quantitative PCR assays. Of the 36 recipients, 26 responded to therapy for acute rejection as indicated by return of serum creatinine to baseline value at one-month post biopsy. The other 10 recipients did not respond to therapy and 9 of 10 went onto loose their allografts within 6-months of the incident acute rejection episode. The Banff biopsy grades were not different among the responders vs. non-responders.
Table 1 demonstrates the urinary cell levels of mRNA for CD25, CD3 and cytotoxic attack molecule, granzyme B, were not significantly different between the two groups. However, levels of FoxP3 were significantly lower in those recipients who did not respond to anti-rejection therapy.Average Log of mRNA Levels/18S rRNA 
SEGene Responders (N=26) Non-Responders (N=10) P FoxP3 4.8 0.41.9 0.60.0012 CD25 7.3 0.46.0 0.90.2 CD3 8.5 0.57.4 0.80.4 GB 7.7 0.57.0 0.80.5
Our data support the idea that FoxP3+ regulatory cells determine the outcome of acute rejection with a paucity of such cells being associated with poor response to anti-rejection therapy and subsequent graft loss.