Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
The purpose of the CTOT-10 study is to evaluate belatacept as maintenance therapy, while minimizing calcineurin inhibitors and corticosteroids in renal transplantation. We designed mechanistic studies to ascertain the effects of these belatacept-based regimens on immune phenotypes and function.
Participants were randomized to one of three study arms. Patients in all groups received perioperative steroids and maintenance MMF. Groups 1 (N=5) and 2 (N=3) received alemtuzumab induction with maintenance tacrolimus or belatacept respectively. Group 3 (N=7) received basiliximab induction, 3 months of tacrolimus and maintenance belatacept. Peripheral blood was collected on Days 0, 28 and 84 post-transplant. Phenotypic characterization of PBMCs was performed using flow cytometric assessment of memory, differentiation, activation and exhaustion.
CD8 T cells from alemtuzumab depleted patients showed a strong trend toward an effector memory RA phenotype at day 28 but returning to baseline distribution by day 84. Similarly, while depleted patients demonstrated a more differentiated (CD27lo, CD28lo) T cell phenotype at day 28, by day 84 the expression patterns had returned to baseline with a mostly undifferentiated (CD27hi, CD28hi) phenotype.
We found a significant increase in recent thymic emigrants (RTE) in depleted compared to non-depleted patients at day 28 though Group 1 exhibited higher frequencies of CD4+ RTE, while Group 2 showed a dramatic increase in CD8+ RTE. Interestingly these RTE populations returned to baseline levels at day 84 despite overall absolute cell numbers still being low. Intriguingly Ki67 expression (a marker for proliferation) remained high from day 28 through day 84 despite normalizing RTE levels. These data could suggest that while early post transplant proliferation reestablished baseline distributions of major population subsets, post day 84 proliferation could serve to increase overall absolute cell numbers back to baseline levels.
Although the CTOT-10 study is limited by small numbers of patients, we found notable differences in the immune phenotypes between the treatment groups, which will be examined in the currently ongoing transplant studies CTOT-15 and CTOT-16.
To cite this abstract in AMA style:Suessmuth Y, Stempora L, Johnson B, Cheeseman J, Morrison Y, Bridges N, Ikle D, Tomlanovich S, Stock P, Mannon R, Newell K, Larsen C, Mehta A. Immune Phenotyping of Peripheral Blood Samples from the CTOT-10 Belatacept Study [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/immune-phenotyping-of-peripheral-blood-samples-from-the-ctot-10-belatacept-study/. Accessed August 9, 2020.
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