Is the intracellular ATP concentration of CD4+ T-Cells a predictive biomarker of immune status in stable transplant recipients?
BACKGROUND
Intracellular ATP (iATP) production in CD4(+)-T cells has been proposed as a biomarker for routine personalized monitoring in transplant recipients. The aim of our study was to measure this biomarker in adult renal and liver transplant recipients receiving moderate immunosuppressive treatment (IST) during the maintenance period and to evaluate whether this biomarker can effectively predict clinical status (stability, rejection, or infection) and drug effect.


METHODS
iATP concentration and trough blood levels of IST were evaluated in 84 adult transplant recipients (50 renal and 34 liver) during the maintenance period. One hundred and fifty healthy donors were also recruited as a control group. In addition, 22 of 34 liver transplant recipients were included in a clinical study in which IST was withdrawn gradually until total elimination.


RESULTS
Most of the patients evaluated had iATP levels in the moderate immune response zone during a posttransplantation maintenance period with no relevant clinical events. iATP levels were significantly lower in transplant patients with infection (n=3) than in those free of infection. In the IST withdrawal study, 10 of 22 liver transplant recipients have achieved complete withdrawal and 12 receive 50% of IST. So far, there have been eight rejections once IST began to be withdrawn. None of these patients had iATP in the strong immune response zone (risk of rejection).


CONCLUSIONS
iATP seems to be more effective in identifying overimmunosuppressed patients with a high risk of adverse events (IST-safety) than in identifying those with a high risk of rejection (IST-efficacy) and should be used in combination with other biomarkers of immunosuppressive effect to improve the efficacy of IST.
Millán
Olga
O
Laboratorio de Farmacología y Toxicología, Centre de Diagnòstic Biomèdic, IDIBAPS, Hospital Clínic, Barcelona University c/Villarroel 170, Barcelona, Spain.
Sánchez-Fueyo
Alberto
A
Rimola
Antoni
A
Guillen
David
D
Hidalgo
Susana
S
Benitez
Carlos
C
Campistol
Josep M
JM
Brunet
Merce
M
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000401:mortality / Q000502:physiology*; D016031:Liver Transplantation / Q000276:immunology / Q000401:mortality / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D012016:Reference Values; D020123:Sirolimus / Q000627:therapeutic use; D015996:Survival Rate; D017741:Survivors; D014181:Transplantation Immunology
D015415:Biomarkers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D009173:Mycophenolic Acid; D020123:Sirolimus