Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Background: mTOR inhibitors stimulate viral-specific memory CD8+ T cell differentiation and increase viral clearance in infected Tx pts. HS pts desensitized (DES) with IVIG + rituximab and alemtuzumab induction (a-CD52) are at increased risk for BKV infection. Here we monitored post-Tx viral infections and viral-specific T cells in pts treated with Eve/Tac. Methods: 16 DES HS Tx pts maintained on Eve (3-8ng/ml)/Tac (2-5ng/ml)+steroid were monitored for viremia by PCR, immune cells and CMV & EBV-specific CD8+ (Tc) or CD4+ T cells (Th) by standard & cytokine flow cytometry. All pts received a-CD52 and anti-viral prophylaxis for 6M. The results from 34 HS pts maintained on Tac (4-7ng/ml)+MMF+steroid served as controls. CMV & EBV >5 copies/PCR, plasma BKV >250 copies/ml, viral-specific T cells >0.2% were considered positive. Results: BKV viremia rate was significantly higher in Eve/Tac than Tac pts (5/16 [31%] vs. 3/34 [9%], p=0.04), while CMV (1/16 [6%] vs. 4/34 [12%], p=0.5) and EBV (2/16 [13%] vs. 1/34 [3%], p=0.18) viremia rates were similar in both groups. All 5 BKV viremias occurred within 3.5M post-Tx. CD8+ (baseline 1.0: 0.05 vs. 0.25, p=0.31 at 3M, 0.08 vs. 0.33, p=0.15 at 6M post-Tx) and CD4+ T cells (0.03 vs. 0.08, p=0.17 at 3M , 0.08 vs. 0.15, p=0.20) were lower in Eve/Tac than Tac pts early post-Tx, while NK cell numbers (0.54 vs. 0.48 at 3M, 0.4 vs. 0.6 at 6M) were similar. More Eve/Tac pts were CMVTc(+) than Tac pts (82% vs. 61%, p=0.22 at 1M, 90% vs. 74%, p=0.12 at 2M), but, the CMVTc levels were similar (3.4% vs. 3.0% at 1M, 4.1% vs. 4.8% at 2M). 70% of Eve/Tac pts were also (+) for EBVTc at 1 and 2 M post-Tx. The CMVTh & EBVTh(+) number were low in both groups during this period. Up to 3 M post-Tx, most pts in both groups showed both viral-Tc and Th(+). All viral infections resolved except 1pt with BK nephropathy. Conclusions: The CD8+ cell number was very low in Eve/Tac pts early post-Tx, suggesting slow T cell recovery. Intact CMVTc activity in Eve/Tac pts may help to minimize CMV viremia. Despite this, BKV viremia was increased in Eve/Tac patients. Frequent viral PCR monitoring, especially at early post-Tx, is essential to prevent chronic viral complications in this patient population.
To cite this abstract in AMA style:Ge S, Kahwaji J, Chu M, Karasyov A, Castro M, Hayrapetyan E, Lovato D, Thomas D, Choi J, Louie S, Vo A, Jordan S, Toyoda M. Assessment of Viral-Specific Memory T Cell Responses and Infection Rates in HLA-Sensitized (HS) Kidney Transplant Patients (Tx Pts) Treated With Everolimus & Low-Dose Tacrolimus (Eve/Tac) [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/assessment-of-viral-specific-memory-t-cell-responses-and-infection-rates-in-hla-sensitized-hs-kidney-transplant-patients-tx-pts-treated-with-everolimus-low-dose-tacrolimus-evetac/. Accessed June 4, 2020.
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