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Transplantation. 2009 Jan 15;87(1):79-86. doi: 10.1097/TP.0b013e31818bbea7.

The effect of the JAK inhibitor CP-690,550 on peripheral immune parameters in stable kidney allograft patients.

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  • 1Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.



CP-690,550 inhibits Janus kinase 3 (JAK3) which mediates signal transduction of receptors of the common gamma-chain cytokines. These cytokines play key roles in lymphocyte function and homeostasis. As part of a phase 1 trial, we evaluated the effect of CP-690,550 on immune parameters.


Stable kidney transplant recipients (n=8) receiving mycophenolate mofetil and prednisolone were treated with CP-690,550, 30 mg twice daily orally for 29 days. Blood samples were collected on days 1 (before first dose), 15, 29 (end of treatment), and 57.


Two patients experienced minor infections (one urinary tract infection and one mild respiratory tract infection). Leukocyte counts remained stable, whereas a mean decrease in hemoglobulin of 8% was measured (P=0.01). CP-690,550 treatment for 29 days resulted in statistically significant changes in the number of circulating CD19+ B cells (P=0.05), CD3- CD16+ CD56+ natural killer-cells (P<0.01), and CD4+ CD25bright+ T cells (P=0.05; one-way analysis of variance). After CP-690,550 treatment on day 15 the number of B cells increased by a mean of 100%, (P=0.04), whereas those of natural killer cells and CD4+ CD25bright+ T cells decreased by 65% (P=0.001) and 38% (P=0.03, t test), respectively, from pretreatment baseline. However, the regulatory capacities of the residual CD4+ CD25bright+ T cells remained unchanged pre- and posttreatment. In addition, in the presence of CP-690,550, the interferon-[gamma] production capacity of peripheral blood mononuclear cells was reduced by 39% (median) compared with predose baseline (P=0.01).


These findings demonstrate the role of JAK3 in the homeostasis and function of select lymphocyte subpopulations. JAK3 inhibition may provide a novel mechanism for the modulation of allogeneic responses in patients after transplantation.

[PubMed - indexed for MEDLINE]
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