Biomarkers of immunoregulatory status in stable liver transplant recipients undergoing weaning of immunosuppressive therapy.
Biomarkers that reflect immune response recovery and predict clinical events during withdrawal or minimization of immunosuppressive therapy have not been evaluated. This study aimed to evaluate whether immune response recovers after withdrawal of long-term immunosuppressive treatment in stable liver transplant patients and to determine whether specific biomarkers reflect immune response reactivity and predict rejection. Pharmacokinetic-pharmacodynamic profiles were determined in 24 patients and 80 healthy donors before immunosuppressive treatment reduction began, at 50%, and at complete withdrawal. In patients who rejected, effector-T-cell response mediated by soluble IFN-γ, %CD4(+)IFN-γ and %CD8(+)IL-2/IFN-γ were significantly increased, while TGF-β1 production and the TGF-β1/IFN-γ ratio were significantly decreased. In patients with rejection, soluble IFN-γ and %CD8(+)IL-2 were significantly higher before immunosuppressive treatment was reduced. Further studies are required, but this battery of biomarkers performed in whole blood could be a useful tool to monitor immunosuppressive treatment minimization or withdrawal protocols and identify patients at increased risk of rejection.
Millán
Olga
O
Unidad de Inmunosupresión, Farmacología, Centro de Diagnóstico Biomédico, IDIBAPS, Hospital Clínico, Universidad de Barcelona c/ Villarroel 170, 08036, Barcelona, Spain.
Benitez
Carlos
C
Guillén
David
D
López
Anna
A
Rimola
Antoni
A
Sánchez-Fueyo
Alberto
A
Brunet
Mercè
M
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D049109:Cell Proliferation; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood*; D007376:Interleukin-2 / Q000097:blood*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood; D010648:Phenylacetates / Q000008:administration & dosage / Q000097:blood; D018809:Proliferating Cell Nuclear Antigen / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology*; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood
D015415:Biomarkers; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010648:Phenylacetates; D018809:Proliferating Cell Nuclear Antigen; D007371:Interferon-gamma; D016572:Cyclosporine; D009173:Mycophenolic Acid; C512803:alpha-methoxy-alpha-phenylacetic acid; D016559:Tacrolimus