Abstract
JAK3 inhibition with the CP-690,550 compound has an immunosuppressive potency in murine models, nonhuman primates and humans. This drug blocks STAT5 activation in most T-cell subpopulations but less effectively in T-regulator cells. In low to moderate risk human kidney transplant recipients, combined with mycophenolate mofetil, steroids and an induction with basiliximab, CP-690,550 proved as effective as calcineurin inhibitors with regard to prevention of acute rejection but better than calcineurin inhibitors with regard to preservation of kidney function and histology. However, at the same time, an increased incidence of overimmunosuppression consequences (cytomegalovirus, BK virus and lymphoproliferation) was observed and led to discontinuation of this specific drug development in kidney transplantation.
Highlights
The results of kidney transplantation have improved dramatically over the past 20 years – much progress has been made with regard to short-term results (1-year patient and graft survival), the attrition rate afterwards has changed minimally if at all [1]
Declaration This article has been published as part of Transplantation Research Volume 2 Suppl 1, 2013: Proceedings of the 12th International Symposium on Transplantation
The full contents of the supplement are available at http://www.transplantationresearch.com/supplements/2/S1
Summary
The results of kidney transplantation have improved dramatically over the past 20 years – much progress has been made with regard to short-term results (1-year patient and graft survival), the attrition rate afterwards has changed minimally if at all [1]. The effect of CP-690,550 on IL-2mediated JAK/STAT5 phosphorylation by CD4+CD25brightFoxP3+CD127−/low regulatory T cells (Tregs) and CD4+CD25– effector T cells (Teffs) was examined in kidney transplant patients [20]. Tofacitinib was equivalent to cyclosporine in preventing acute rejection, was associated with improved renal function and less chronic allograft histological injury, but developed serious side effects at the doses evaluated with an exposure–response relationship. This not unexpectedly high incidence of infectious complications is probably due to the broad JAK3-inhibited gamma-chaindependent cytokines such as IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 [22]. It would have been very interesting to try to keep the potent immunosuppressive effect together with the absence of nephrotoxicity either by avoiding high drug exposure, which seemed to correlate with infectious complications, or by modifying the companion drug or its dosage
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
