Elevated Cytotoxic T Cells is Associated with Allosensitization of Patients Supported by a Continuous-Flow Left Ventricular Assist Device

Abstract

Introduction Use of CFLVADs as a BTT continues to increase. The mechanisms of host immune system activation following implantation leading to allosensitization complicating transplantation outcomes are not well understood. Hypothesis We hypothesize that pre-implant cell profiles may predict post-implant allosensitization. Methods Plasma and PBMC samples were collected before implant (D0), 48 hours post-implant (D2) and 8 days post-implant (D8) in 12 CFLVAD patients. HLA class I and II antibody profiles were obtained pre and post-implant. Calculated panel of reactive antibodies (cPRA) were calculated using the OPTN calculator. Plasma aliquots were randomized and performed in duplicate. Lymphocyte phenotypes were analyzed by multiparameter flow cytometry across 3 randomized panels. Results Mean age of patients was 53.6±15.3 years, 50% were female and 33% had ischemic cardiomyopathy. Following implant there was a significant increase of Treg cells (CD4+Foxp3+CD25+ 1.07±0.39 p=0.005), T effector cells (CD4+Foxp3−CD25+ 13.2±2.83 p=0.0007) and B cells (CD3−CD19+ 7.17±2.93 p=0.032). This was accompanied with a decrease in CD3+ T cells (-10.1±3.69 p=0.019), cytotoxic T cells (CD3+CD8+ -3.28±1.12 p=0.014), and NK cells (CD3−CD19−CD56+ -3.86±1.72 p=0.047). Three patients had an increase in cPRA post-implant. All 3 patients had significantly increased cytotoxic T cells compared to patients with no increase (D0 18.4±2.46 vs 7.69±5.79 p=0.013); (D2 15.8±3.12 vs 6.74±3.61 p=0.012); (D8 13.9±3.64 vs 4.83±2.99 p=0.002) ( Figure 1 ). A significant increase in the plasma cytokines IL-6 (D0 79.7 D2 1320 D8 240 p Conclusion We show an impaired cellular immunity characterized by an acute rise in Treg, T-effector cells as well as B cells while the tissue aggressive response decreased. IL-6, IL-8 and G-CSF increased significantly post-implant in sensitized patients. Surprisingly, high CD8+ T cells pre-implant were associated with an increased cPRA in our cohort. CD8+ T cells in these patients decreased after implant but remained 2-fold higher than those patients with no increase in cPRA. Higher levels of cytotoxic T cells pre-implant may predict post CFLVAD implant allosensitization. Characterizing pre-implant cell profiles may be useful in identifying appropriate CFLVAD recipients.