Background: PEBV infection is associated with high risk for development of PTLD. Recent studies report a critical role for IL-21 in sustaining viral-specific Tc activity during chronic viral infections. Here we measure the plasma levels of anti-viral cytokines (IL-21, IFNg, IL-17A) (pg/ml) and EBVTc in pediatric kidney Tx pts and correlated these findings with EBV infection and PTLD status. Method: Archived plasma obtained at multiple time points post-Tx from 48 pts who had PEBV (10), acute EBV (6, AEBV) and no EBV viremia (32, NEBV) were submitted for cytokine luminex assay. EBV DNA was quantified by PCR, and EBVTc by an intracellular cytokine flow cytometry. PEBV was defined as EBV viremia >10 copies/PCR for >3months. Results: Mean (155±218 vs. 12±8, p<0.05) and peak (201±260 vs. 20±10, p<0.05) EBV DNA levels were significantly higher in PEBV than AEBV groups. The IL-21 (199±108 vs. 94±51, p<0.05) and IL-17A (76±41 vs. 43±59, p<0.05) levels were significantly higher in PEBV than NEBV. IFNg showed a similar trend (104±133 vs. 67±251, p=0.10), but not statistically significant. The IL-21 levels in AEBV were 119±54 and were also significantly higher than those in NEBV pts (p<0.05), but were significantly lower than those in PEBV pts (p<0.05). There was no difference in the IL-17A and IFNg levels between AEBV and NEBV. The IL-21 levels significantly increased with the EBV DNA levels (0 copy: 101±67, 0-<5: 139±94, 5-50: 170±114, >50: 180±97: p<0.05), but IL-17A or IFNg did not. Among 9 PEBV pts w/ EBVTc results, all showed EBVTc (+) and anti-EBV antibody (+). None of AEBV and PEBV developed PTLD. Conclusions: 1) EBV DNA levels were significantly higher during PEBV than AEBV, 2) IL-21 levels increased during PEBV and was much higher than seen with AEBV, 3) The levels of IL-21, but not IL-17A or IFNg, were significantly higher at high EBV DNA levels observed during PEBV. These results demonstrate an important role of IL-21 during PEBV and suggest that EBVTc together with IL-21 and anti-EBV antibody control EBV proliferation during PEBV and likely preventing PTLD.
To cite this abstract in AMA style:Ge S, Puliyanda D, Junji W, Karasyov A, Kamil E, Lovato D, Monette R, Vikman S, Jordan S, Toyoda M. High Levels of Plasma IL-21 Together with EBV-Specific Cytotoxic T Cells (EBVTc) May Contribute Avoidance to Post-Transplant (Tx) Lymphoroliferative Disorder (PTLD) in Pediatric Kidney Tx Patients (pts) Who Had Persistent EBV Infection (PEBV) [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://atcmeetingabstracts.com/abstract/high-levels-of-plasma-il-21-together-with-ebv-specific-cytotoxic-t-cells-ebvtc-may-contribute-avoidance-to-post-transplant-tx-lymphoroliferative-disorder-ptld-in-pediatric-kidney-tx-patients-pt/. Accessed November 19, 2017.
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