Presented at:
American Transplant Congress, Washington, DC,
June 2, 2003
Dendritic cell subset ratio in peripheral blood correlates with successful withdrawal of immunosuppression in liver transplant patients
George V. Mazariegos, Alan Zahorchak, Adriana Zeevi, Bridget Flynn, Alison J. Logar, Jorge Reyes, Angus Thomson
University of Pittsburgh Medical Center, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA
AIM: To examine whether predominance of the putatively tolerogenic dendritic cell (DC) 2 subset correlates with clinical tolerance following liver transplantation (LTx).
METHODS: PMBC from patients (pts.) who have been successfully withdrawn from immunosuppression (IS) following LTx (Group A), those who are undergoing propsective drug weaning (Group B), and those in whom drug withdrawal failed or has not been attempted (Group C) were isolated from peripheral blood by Ficoll density centrifugation. Total DC were identified as HLA-DR+ and lineage marker (CD3, CD14, CD19, CD20) negative on four-color flow cytometric analysis. Subpopulations of IL-3R alpha HLA-DR+ lin-/{precursor (p)DC2} and CD4+ CD11c+HLA-DR+lin-(pDC1) were further quantified. 13 adults served as healthy controls.
RESULTS: 40 clinically stable pts with normal liver function were eligible for study. Group A pts have been off IS for a mean of 3.3 yrs. Group B pts are undergoing uninterrupted drug weaning for a mean of 1.3 yrs. Group C pts failed drug withdrawal due to rejection or recurrent autoimmune disease (n=6) or never had drug withdrawal attempted (n=5). Mean patient demographic data, % DC, and DC subsets are listed in Table 1. Statistical analysis was by Mann-Whitney U test.
CONCLUSION: This investigation demonstrates that the plasmacytoid DC lineage (pDC2) is more prevalent in patients successfully withdrawn from IS as well as those on low levels of IS and may prospectively allow identification of clinically tolerant patients.
| Group | A. Off IS |
B. Prospective Weaning |
C. Drug Withdrawal Failed or Not Attempted |
Normal Adult Controls |
| # of pts | 6 |
23 |
11 |
13 |
| Age @ LTx (yr) | 6.5 (0.4-16.3) |
2.4 (0.2 - 9) |
29.1 (1.6-61) |
N/A |
| Current age (yr) | 16.2 (3-25.8) |
11.6 (2-24) |
34.8 (2.9-65.2) |
34.3 (25-53) |
| Time Off Drugs/Weaning (yr) | 3.3 (0.8-7.9) |
1.3 (0.1-9.7) |
N/A |
N/A |
| % pDC | 1.9 (.86-3.3) |
2.4 (.7-10.5) |
2.9 (0.5-8.2) |
2.1 (.6-4.5) |
| % pDC2 | 21.8 (7.1-43.6)# |
17.1 (6.9-37) |
4.7 (0.9-13.5) |
13 (5.1-37.9) |
| %pDC1 | 53.8 (43-74.5)* |
61.3 (34.7-81.8) |
73.1 (50-91.4) |
64.4 (35.2-80.8) |
| %pDC2/%pDC1 | .49 (.1-1.1)^ |
0.31 (.1-.86) |
0.07 (0.014-0.18) |
.26 (.07-1.1) |
| Group A vs. Group C: #p<0.003; *p<.016, ^p<.001 | ||||
ACKNOWLEDGEMENT: This research was performed as a project of the Immune Tolerance Network, a 7 year clinical reasearch project headquartered at UCSF and supported by NIAID, NIDDK and the Juvenile Diabetes Research Foundation.