Phospho-specific flow cytometry for pharmacodynamic monitoring of immunosuppressive therapy in transplantation

Carla Baan,Ramin Vafadari,Anne Bouvy,Willem Weimar

doi:10.1186/2047-1440-1-20

Carla Baan, Ramin Vafadari + Show 2 more

Open Access

https://doi.org/10.1186/2047-1440-1-20

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Journal: Transplantation Research	Publication Date: Nov 16, 2012
Citations: 40	License type: CC BY 2.0

Affiliation: Erasmus MC

Abstract

Organ transplant recipients frequently suffer from toxicity or from lack of efficacy of immunosuppressive drugs, which can be attributed to individual variations in drug sensitivity. This problem can be resolved by applying pharmacodynamic monitoring that focuses on measuring the biological effects of drugs. Here we discuss the new technique called phospho-specific flow cytometry to monitor the activity of intracellular immune signaling pathways at the single-cell level in whole blood samples. Through this tool the efficacy of immunosuppressive medication can be assessed, novel targets can be identified, and differences in drug sensitivity between cells and patients can be clarified.

Highlights

To prevent and to treat alloreactivity, transplant recipients are on immunosuppressive medication for life
Standard immune suppressing regimens consists of a calcineurin inhibitor (CNI, e.g., tacrolimus/ cyclosporine), an inosine monophosphate dehydrogenase inhibitor and corticosteroids
Based on the results found in experimental models, it is expected that these novel immunosuppressants are more specific than Calcineurin inhibitor (CNI)

Summary

Background

To prevent and to treat alloreactivity, transplant recipients are on immunosuppressive medication for life. Phospho-specific flow cytometry: a novel tool to measure intracellular signaling pathways With the recent advances in flow cytometry, the number of parameters that can be measured has been largely expanded These new parameters allow us to monitor immune responses functionally at rest and following activation at the single-cell level. Apart from the analysis of typical target signaling molecules, e.g., NF-κB in sotrastaurin-treated patients, mTOR in sirolimus and p38 MAPK signaling in CNI-treated kidney transplant patients, this phospho-specific flow cytometry technique can be used to study T-cell function before and after rATG induction treatment and to further unravel the mechanism of action of immunosuppressive agents like CNI [26,32]. Addressing these limitations will further improve the utility of phospho-specific flow cytometry for clinical applications

Conclusions

Cantrell DA