Failure of immunosuppressive drug levels to predict T-cell reactivity in pediatric transplant patients.
OBJECTIVE
In children, therapeutic management of immunosuppression relies on allograft function, drug levels, and clinical insight. Using a Food and Drug Administration-approved test for T-cell response, T-cell activation in vitro can be measured to monitor the immune response.


METHODS
In a retrospective study, 92 posttransplant children who received either a liver and/or kidney transplant and were followed by routine screening had their T-cell response tested by the Cylex ImmuKnow assay (Columbia, MD). After phytohemagglutinin-L stimulation of T-cells, adenosine triphosphate (ATP) concentrations were measured. In this assay, light emission at lambda = 562 nm is proportional to the ATP concentration (ng/mL). Immunosuppressive drug trough levels were also measured. Quantitative real-time polymerase chain reaction Epstein-Barr virus (EBV) viral titers were determined for 2 patients.


RESULTS
Separating the results into younger than 12 years and 12-year or older populations, we found that for the younger than 12 years, 28% of patients were in the low immune function category, 47% in the moderate, and 25% in the high category. For the 12 years or older, 25% of patients were in the low immune function category, 47% in the moderate, and 28% in the high category. The immune function distribution was not different (P = not significant) between the younger than 12 years and 12-year or older groups. Tacrolimus trough levels were 6.3 +/- 2.4 ng/mL for younger than 12 years and 5.6 +/- 3.3 ng/mL for 12 years or older (P = not significant), and rapamycin was similar, but both showed no correlation to immune function. We observed increased ATP values with decreased EBV viral loads.


CONCLUSIONS
These results suggest that tacrolimus and/or rapamycin levels do not adequately determine the biologic effect of immunosuppression. We expect that future T-cell activation monitoring will allow us to diminish rejection and infection events posttransplantation and lead to a healthier pediatric transplant population.
Nemours Biomedical Research, Molecular Genetics, Cellular and Tissue Transplantation, Wilmington, DE 19803, USA.
Valerie B
VB
Sampson
Stephen P
SP
Dunn
Beth
B
Rymeski
James
J
Malatack
Nancy H
NH
Rong
Louise
L
Flynn
Leslie J
LJ
Krueger
D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology / Q000379:methods; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology / Q000379:methods; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D016377:Organ Transplantation / Q000009:adverse effects* / Q000379:methods; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D020123:Sirolimus / Q000008:administration & dosage / Q000097:blood; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood; D014181:Transplantation Immunology / Q000502:physiology*
D007166:Immunosuppressive Agents; D000255:Adenosine Triphosphate; D020123:Sirolimus; D016559:Tacrolimus