title: Phosphospecific flow cytometry for pharmacodynamic drug monitoring: analysis of the JAK-STAT signaling pathway.
abstract: Cytokines of the IL-2 receptor family act via activation of the JAK-STAT (janus tyrosine kinase-signal transducer and activator of transcription) signaling pathway. These cytokines are pivotal for the development and function of lymphocyte subsets involved in the immune response after organ transplantation including T, B and natural killer cells. The new small drug molecule and JAK1/3 inhibitor, tofacitinib, is currently being tested in phase II and III clinical trials for rheumatoid arthritis, psoriasis and in organ transplantation. This agent specifically targets the JAK-STAT signaling pathway. Here we discuss phosphospecific flow cytometry as a novel tool to monitor the JAK-STAT signaling pathway in kidney transplant patients and speculate that through the use of this pharmacodynamic tool the efficacy of immunosuppressive drugs can be assessed enabling optimization of the immunosuppressive therapy for individual transplant patients.
authors.affiliation: Department of Internal Medicine, Erasmus MC, University medical Hospital Rotterdam, The Netherlands. r.vafadari@erasmusmc.nl
authors.forename: Ramin
authors.initials: R
authors.lastname: Vafadari
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
mesh_terms: D000818:Animals; D016903:Drug Monitoring; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D050791:STAT Transcription Factors; D053612:Janus Kinases