ABSTRACT
BACKGROUND: Patients with end-stage kidney disease (ESKD) wait roughly 4 years for a kidney transplant. A potential way to reduce wait times is using hepatitis C virus (HCV)-viremic kidneys. OBJECTIVE: As preparation for developing a shared decision-making tool to assist patients with ESKD with the decision to accept an HCV-viremic kidney transplant, our initial goal was to assess the feasibility of using The Gambler II, a health utility assessment tool, in an ambulatory dialysis clinic setting. Our secondary goals were to collect health utilities for patients with ESKD and to explore whether the use of race-matched versus race-mismatched exemplars impacted the knowledge gained during the assessment process. METHODS: We used The Gambler II to elicit utilities for the following ESKD-related health states: hemodialysis, kidney transplant with HCV-unexposed kidney, and transplantation with HCV-viremic kidney. We created race exemplar video clips describing these health states and randomly assigned patients into the race-matched or race-mismatched video arms. We obtained utilities for these 3 health states from each patient, and we evaluated knowledge about ESKD and HCV-associated health conditions with pre- and postintervention knowledge assessments. RESULTS: A total of 63 patients with hemodialysis from 4 outpatient Dialysis Center Inc sites completed the study. Mean adjusted standard gamble utilities for hemodialysis, transplant with HCV-unexposed kidney, and transplantation with HCV-viremic kidney were 82.5, 89, and 75.5, respectively. General group knowledge assessment scores improved by 10 points (P<.05) following utility assessment process. The use of race-matched exemplars had little effect on the results of the knowledge assessment of patients. CONCLUSIONS: Using The Gambler II to collect utilities for patients with ESKD in an ambulatory dialysis clinic setting proved feasible. In addition, educational information about health states provided as part of the utility assessment process tool improved patients' knowledge and understanding about ESKD-related health states and implications of organ transplantation with HCV-viremic kidneys. A wide variation in patient health state utilities reinforces the importance of incorporating patients' preferences into decisions regarding use of HCV-viremic kidneys for transplantation.
ABSTRACT
Trypanosoma cruzi infection is controlled but not eliminated by host immunity. The T. cruzi trans-sialidase (TS) gene superfamily encodes immunodominant protective antigens, but expression of altered peptide ligands by different TS genes has been hypothesized to promote immunoevasion. We molecularly defined TS epitopes to determine their importance for protection versus parasite persistence. Peptide-pulsed dendritic cell vaccination experiments demonstrated that one pair of immunodominant CD4+ and CD8+ TS peptides alone can induce protective immunity (100% survival post-lethal parasite challenge). TS DNA vaccines have been shown by us (and others) to protect BALB/c mice against T. cruzi challenge. We generated a new TS vaccine in which the immunodominant TS CD8+ epitope MHC anchoring positions were mutated, rendering the mutant TS vaccine incapable of inducing immunity to the immunodominant CD8 epitope. Immunization of mice with wild type (WT) and mutant TS vaccines demonstrated that vaccines encoding enzymatically active protein and the immunodominant CD8+ T cell epitope enhance subdominant pathogen-specific CD8+ T cell responses. More specifically, CD8+ T cells from WT TS DNA vaccinated mice were responsive to 14 predicted CD8+ TS epitopes, while T cells from mutant TS DNA vaccinated mice were responsive to just one of these 14 predicted TS epitopes. Molecular and structural biology studies revealed that this novel costimulatory mechanism involves CD45 signaling triggered by enzymatically active TS. This enhancing effect on subdominant T cells negatively regulates protective immunity. Using peptide-pulsed DC vaccination experiments, we have shown that vaccines inducing both immunodominant and subdominant epitope responses were significantly less protective than vaccines inducing only immunodominant-specific responses. These results have important implications for T. cruzi vaccine development. Of broader significance, we demonstrate that increasing breadth of T cell epitope responses induced by vaccination is not always advantageous for host immunity.
