Biomarkers of the immunomodulatory effect of immunosuppressive drugs in transplant recipients.
Nowadays, monitoring of the immunosuppressive therapy received by solid organ transplant recipients is based on measuring drug blood levels to achieve concentrations within the established therapeutic range. This strategy largely prevents the toxicity associated with this kind of treatment but is insufficient to determine the individual response in each patient or to tailor the dose to each patient's real requirements. In the field of solid organ transplantation, new approaches able to reflect the individual responses produced in each patient are required to monitor immunosuppressive therapy and to improve the efficacy and safety of treatment. Thus, in the last few years, preliminary studies evaluating new specific biomarkers of the biologic effect of immunosuppressive drugs (pharmacodynamic monitoring) have been carried out. The results of these pilot studies show the potential of monitoring of these specific biomarkers to improve the safety and efficacy of immunosuppression, although the complexity of these analyses and the lack of standardized methodologies currently limit the routine application of this technique. Based on the previous studies performed to date on biomarkers, which included a small number of patients, no conclusions can be drawn as to which are the most appropriate biomarkers to prevent organ rejection or adverse events. Consequently, these biomarkers need to be validated in multicenter clinical trials. The present article reviews some biomarkers that have been proposed to evaluate currently approved immunosuppressants, such as target enzymes, cytokines, lymphocyte activation biomarkers, and cellular immune response, as well as the most promising results in this field.
Millán
Olga
O
Laboratorio de Farmacología (CDB), Servicio de Bioquímica y Genética Molecular, Hospital Clínic, IDIBAPS, Universidad de Barcelona, 08036 Barcelona, Spain.
Urtasun
Nerea
N
Brunet
Mercè
M
D015415:Biomarkers; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D019737:Transplants
D015415:Biomarkers; D007166:Immunosuppressive Agents