Purpose: The effects of Alemtuzumab (anti-CD52) on immune cell subpopulations was evaluated to better understand themechanisms of action of this drug.
Methods: The Immune Tolerance Network is conducting a prospective, trial of adult, HepC-, Hep B -liver allograft recipients using induction of Alemtuzumab (30 mg on day 0 and 4) followed by maintenance immunosuppression with tacrolimus. Five color flow cytometry was used to measure the kinetics of PBMC depletion and reconstitution in peripheral blood from 14 of 27 total enrolled subjects at timepoints corresponding to baseline, 1, 3, 6, and 9 months post-transplant (13 of the 27 had not progressed sufficiently to evaluate at later timepoints). For each cell population, percent depletion from baseline was computed.
Results: Shown is a table percent baseline values of major subpopulations from peripheral blood of patients.
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Table 1. Median Percent of Baseline Value |
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Months Post-Transplant |
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|
Cell Population |
1 |
3 |
6 |
9 |
|
T cells |
3% |
9% |
53% |
69% |
|
CD4 T cells |
1% |
7% |
21% |
27% |
|
CD8 T cells |
2% |
8% |
120% |
139% |
|
CD4 T cells, Memory |
2% |
9% |
43% |
57% |
|
CD4 T cells, Naïve |
1% |
2% |
11% |
29% |
|
CD8 T cells, Memory |
1% |
7% |
128% |
443% |
|
CD8 T cells, Naïve |
6% |
7% |
112% |
201% |
|
CD52 B cells |
1% |
24% |
67% |
81% |
|
CD52 T cells |
0% |
7% |
39% |
74% |
|
CD52 NK cells |
23% |
93% |
119% |
121% |
|
CD25hiCD4 T cells |
2% |
17% |
24% |
31% |
|
NK cells |
72% |
99% |
94% |
112% |
|
B cells |
2% |
32% |
99% |
89% |
|
Memory B cells |
7% |
40% |
209% |
170% |
|
Myeloid DC |
53% |
72% |
79% |
80% |
|
Plasmacytoid DC |
24% |
29% |
35% |
38% |
|
Monocytes |
98% |
48% |
46% |
46% |
Conclusion: Our results show that: (1) NK cells are strikingly resistant to depletion; (2) T cell reconstitution at 6 and 9 months is dominated by CD8 cells, especially CD8 memory cells; and (3) B cell reconstitution similarly favors memory B cells.
The resistance of NK cells to depletion and the early appearance of memory CD8 T and B cells to levels above baseline may explain the low incidence of opportunistic infections reported after induction with Alemtuzumab, and may also account for early rejection events reported in renal transplant recipients treated with this drug. Overall these results provide a detailed picture of the effects of Alemtuzumab on immune cell subpopulations, which may lead to a better understanding of clinical effects of this drug. Results will be updated as more data become available.