The impact of EBV load on T-cell immunity in pediatric thoracic transplant recipients.
BACKGROUND
Immunologic monitoring of pediatric transplant (Tx) recipients, who are at increased risk of Epstein-Barr virus (EBV)-driven posttransplant lymphoproliferative disease, is an important goal in clinical transplantation. Here, we investigated the impact of EBV load on T-cell immunity from pediatric Tx recipients, using clinically applicable tests for improved assessment of T-cell immune competence.


METHODS
Thirty-five asymptomatic pediatric thoracic Tx patients were categorized into three groups according to their EBV load levels as follows: undetectable viral load (UVL), chronic low viral load (LVL) and chronic high viral load (HVL). Global and EBV-specific T-cell immunity were assessed by ATP release using Cylex Immuknow and T Cell Memory assays.


RESULTS
UVL patients exhibited normal ATP release to Concanavalin A (ConA) and phytohemagglutinin (PHA; 190+/-86 ng/mL, 328+/-163 ng/mL) and detectable EBV-specific (37+/-34 ng/mL) ATP responses. LVL patients displayed significantly stronger responses to ConA (373+/-174 ng/mL), PHA (498+/-196 ng/mL) and EBV (152+/-179 ng/mL), when compared with UVL or to HVL patients (ConA 185+/-114 ng/mL, PHA 318+/-173 ng/mL, and EBV 33+/-42 ng/mL). Moreover, HVL patients displayed significant inverse correlation between CD4+ T-cell ATP levels and EBV loads.


CONCLUSIONS
Evaluation of global and EBV-specific T-cell immunity provides a rapid assessment of patients' immune competence. It is still unclear whether selective oversuppressed ATP release by CD4+ T cells reflects HVL patients at risk of posttransplant lymphoproliferative disease. Further longitudinal studies will determine the importance of Immuknow test in identifying asymptomatic HVL patients vulnerable to EBV complications.
Macedo
Camila
C
Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Zeevi
Adriana
A
Bentlejewski
Carol
C
Popescu
Iulia
I
Green
Michael
M
Rowe
David
D
Smith
Louise
L
Webber
Steve
S
Metes
Diana
D
D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis / Q000276:immunology / Q000821:virology*; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D016041:Heart-Lung Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D016040:Lung Transplantation / Q000009:adverse effects*; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000821:virology*; D008297:Male; D016133:Polymerase Chain Reaction; D014184:Transplantation, Homologous; D019562:Viral Load; D055815:Young Adult
D000914:Antibodies, Viral; D004279:DNA, Viral; D000255:Adenosine Triphosphate