title: Intracellular IFN-γ and IL-2 expression monitoring as surrogate markers of the risk of acute rejection and personal drug response in de novo liver transplant recipients.
abstract: Biomarker monitoring is needed in transplantation to reflect individual response to immunosuppressive drugs and graft outcome. We evaluated intracellular expression and soluble production of interferon-(IFN)-γ and interleukin-(IL)-2 as predictive biomarkers of acute rejection (AR) and personal drug response. Pharmacokinetic-pharmacodynamic profiles were determined in 47 de novo liver recipients treated with tacrolimus, mycophenolate mofetil and prednisone. Of the 47 patients, AR occurred in nine. There were no differences in drug concentrations between rejectors and non-rejectors. A pre-transplantation cut-off value of 55.80% for %CD8(+)-IFN-γ(+) identified patients at high risk of AR with a sensitivity of 75% and a specificity of 82%. In the first week post-transplantation, patients with a % inhibition for soluble IFN-γ, %CD8(+)-IFN-γ(+) and %CD8(+)-IL2(+) lower than 40% developed AR, showing low susceptibility to immunosuppressive drugs. Therefore, effector-T-cell response monitoring may help physicians to identify personal response to treatment and patients at high risk of AR.
authors.affiliation: Farmacología y Toxicología, Centro de Diagnóstico Biomédico, IDIBAPS, Hospital Clínico, Universidad de Barcelona, C/Villarroel 170, 08036 Barcelona, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Millán
authors.forename: L
authors.initials: L
authors.lastname: Rafael-Valdivia
authors.forename: E
authors.initials: E
authors.lastname: Torrademé
authors.forename: A
authors.initials: A
authors.lastname: López
authors.forename: V
authors.initials: V
authors.lastname: Fortuna
authors.forename: S
authors.initials: S
authors.lastname: Sánchez-Cabus
authors.forename: Y
authors.initials: Y
authors.lastname: López-Púa
authors.forename: A
authors.initials: A
authors.lastname: Rimola
authors.forename: M
authors.initials: M
authors.lastname: Brunet
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D003710:Demography; D004198:Disease Susceptibility; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D011241:Prednisone / Q000493:pharmacokinetics / Q000627:therapeutic use; D012307:Risk Factors; D012995:Solubility; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007371:Interferon-gamma; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus