Presented at:
World Transplant Congress 2006
Boston, MA, TX, July 22-27, 2004

Upregulation of FoxP3 in renal transplantation after antibody induction regimens with and without bone marrow or stem cell infusions (ITN Protocol #022ST)

Cirocco R, Carreno M, Mathew J, Vallone T, Rosen A, Burke GW, Ciancio G, Kleiner G, Esquenazi V, Miller J

University of Miami School of Medicine and the Veterans Affairs Administration Hospital, Miami, Florida, USA

By monitoring levels of the regulatory molecule FOX P-3 mRNA after transplant, the profile of a regulatory state may be elucidated. We compared four different antibody induction (AbI) groups of kidney transplant recipients that had: 1) Daclizumab (Dac), 2) Thymoglobulin (Thy), 3) Alemtuzumab (C1H), 4) C1H + Donor Hematopoietic Stem Cells (DHSC) vs  ‘normal’ lab volunteers (‘Normals’) for levels of FOX P-3.  We also studied kidney recipients that had perioperatively received  whole “non-selected” donor bone marrow cells (DBMC) as compared with non-DBMC recipients, both groups with normal function after 10 years (10 yr DBMC vs 10 yr non-DBMC).  CD3+ cells from whole blood were positively selected and C-DNA analyzed for levels of human FOX P-3 and GAPDH mRNA by real time PCR. These were expressed as copies / 5000 CD3+ cells. 

The following findings occurred (Table1): 1) All AbI groups had higher FOX P-3 levels than ‘Normals’ (p=<0.03). This was associated with higher numbers of CD4+CD25+ cells in these groups;  2) C1H induction resulted in statistically higher levels of FOX P-3 than AbI groups 1 and 2 (p=0.03 and 0.002 respectively); 3) Ten year DBMC had statistically higher levels of FOX P-3 than 10 yr non-DBMC (p=0.006);   4) In the C1H + DHSC group there were too few patients for statistical correlation (n=4) when compared with Dac, Thy, and C1H, but the levels were significantly higher than ‘Normals’ (P=<0.001) providing preliminary evidence that this group also has a prominent regulatory state (without rejection episodes). In conclusion the monitoring of FOX P-3 (and other regulatory molecules) may be beneficial in defining an immuno-regulatory state in transplant recipients.

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