Monday, July 5, 2010

Photopheresis therapy for renal allograft rejection?

The technique involves three stages: 1-leucapheresis, 2- photoactivation with photosensitizer plus UV A irradiation, and 3- re-infusion of the buffy coat.

Extra Corporal Photopheresis (ECP) was first introduced for the treatment of Cutaneous T-Cell Lymphoma. Now has been widely used in the treatment of acute allograft rejection; most extensively in cases of cardiac transplant rejection. It has also shown success and high efficacy in reversing renal allograft rejection as well. Only one cohort study has been done by Jardine et al; ECP been used in 10 kidney recipients with therapy resistant rejection, and to our surprise, it showed that rejection has been resolved in all patients treated with ECP!

The exact mechanism of action remains unclear, but believe it has an immunomodulatory rather than immunosuppressive effect: The irradiation therapy induces high rate of apoptosis of the T-cells with sparing of the monocytes, and this eventually creates changes in the patient’s cytokine profile towards “type 2” cytokines; with significant increase of IL-5 and decrease of IFN-Gamma - “which is associated with allograft rejection!” also, it has a stimulatory effect on the T-regulatory cells as well..

Safety profile is excellent with <1% adverse effect, considered more safe than any other modality of apheresis!

ECP been mainly used for CTCL, and GVHD. Also, has been used in other autoimmune diseases including MS, scleroderma, DM-1, RA, psoriasis, Crohn’s, Nephrogenic Fibrosing Dermopathy. ECP is an effective, tolerable, and safe immunomodulatory therapy that can be used theoretically for resistant renal allograft rejection “T-cell rejection”. We still need more data and large cohort trials for this promising technique/therapy.

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