Presented at:
31st ASHII Annual Meeting
San Diego, CA, October 17, 2006
Precursor dendritic cell subsets in kidney allograft recipients after induction with alemtuzumab (C1H) vs thymoglobulin (Thy) vs daclizumab (Dac) vs A C1H recipient given donor specific stem cells (DHSC)
Carreno M, Ciancio G, Burke GW, Cirocco R, Gomez C, Salma F, Mathew J, Jin Y, Miller J, Esquenazi V
University of Miami and the VA Medical Center, Miami, FL
Introduction: Increased circulating precursor dendritic cell subset ratios (pDC2:pDC1) may play a role in peripheral transplantation tolerance. In this study we analyzed dendritic cell subsets, CD11c+ (pDC1) vs CD123+ (pDC2) and their ratios, i.e. pDC2:pDC1 in renal transplant recipients treated with C1H vs Thy vs Dac. Additionally we compared these in a recipient given DHSC plus the C1H (Immune Tolerance Network protocol), now 15 months postoperatively.
Methods: Of 121 recipients, 41 received C1H induction together with half dose maintenance immunosuppression (IS) with Tacrolimus (Tac) (converted to Sirolimus), MMF, but no steroids; 40 received Thy and 40 received Dac. The latter two groups received full dose Tac (no sirolimus), MMF, and steroids. A cocktail of monoclonal antibodies (Lin-1 FITC, CD123 PE, HLADRw PerCP and CD11c APC) was used to quantify pDCs pre-Tx and at monthly intervals postoperatively.
Results: Rejection free C1H patients showed a significant increase (from pre-transplant- p<0.02) in the pDC2:pDC1 ratio compared to rejection free Thy or Dac groups. Moreover, of most interest, a consistently (2-3 fold) higher pDC ratio was seen in the (rejection free) DHSC-C1H protocol recipient. (All patients with rejection had significantly lower values)
Conclusions: A significant increase of pDC2 and reduced pDC1 (especially in the DHSC-C1H recipient) was consistent with a rejection free course that might allow IS withdrawal. Protocol biopsy data will also be presented.