The Differential Effects of 3 Different Immunosuppressive

Overview

The study is a laboratory investigation comparing the regulatory effects of different immunosuppressive therapies in an in vitro human MLR assay of selecting specific immunosuppressive therapy to promote a regulatory profile and determining possibly newer accepted dosing and drug concentrations for agents most associated with this regulatory profile.

Life-long immunosuppressive (IS) therapy is typically required in the great majority of organ transplants. Immunobiologically correct IS dosing, tapering to low levels and/or monotherapy could lower the incidence of complications related to IS and improve long term graft and patient survival. The current standard of IS care for liver transplant recipients are the calcineurin-inhibitors (CNIs) tacrolimus (TAC) and cyclosporine (CSA), although alternative IS drugs such as mycophenolate mofetil (MMF) and sirolimus (SRL) are available for use in select patients. This is also true for kidney, pancreas and heart transplant recipients, with TAC being favored in each case. The ideal IS agent is one that can be given at low levels such that both rejection and long term toxicity are minimized. Directly related to IS minimization might be the development of a regulatory, "tolerance profile", as assessed by ex vivo immunophenotyping and functional assays that might test these specific IS agents singly, in combination or even in sequence. Human Tregs and DCregs can be more predominantly generated in the presence of one of three IS agents with different modes of action, i.e., TAC, MMF or SRL, and in different conditions of antigen presentation and alloimmune incompatibility. This is a bench protocol studying the effects of TAC, MMF and SRL on pre operative living renal recipient donor pair.

Conditions

Eligibility

Locations (1)

Outcomes