quiz A559C561. which may optimize outcomes in the clinic. and studies in monkeys . The agent’s polyclonal nature enables it Etamivan to display specificity towards a wide variety of antigens expressed on the surface of T cells, B cells, dendritic cells, NK cells and endothelial cells including those involved in immune response, T-cell activation, proliferation, apoptosis, signal transduction, cell adhesion and trafficking [6C8]. The precise mechanism of action underlying the immunosuppressive efficacy of rabbit (r)ATG in solid organ transplantation recipients is unknown at present, although has been primarily attributed to T-cell depletion. Data from studies suggest that rATG modulates the expression of various lymphocyte surface antigens resulting in apoptosis, antibody-dependent cytolysis or complement-dependent lysis. Lymphocyte depletion with rATG has been further demonstrated in adult renal transplant patients in several randomized, comparative clinical studies (n = 26C277) [9C12], with repopulation reported to take at least 3 months . More recently, data from preclinical and clinical studies suggest that rATG therapy may induce the expansion and enrichment of certain regulatory T-cell subsets [14,15]. Clinical efficacy Rabbit antithymocyte induction in combination with tacrolimus-based immunosuppressive therapy is more effective in preventing episodes of acute renal graft rejection than with tacrolimus-based therapy without induction, as reported by primary end point data from two randomized, open-label, multicenter trials [16,17]. Moreover, the median time to biopsy-proven acute rejection (BPAR) was 1 week longer in rATG induction than in non-induction recipients; however, it should be noted that there was no significant differences between induction Etamivan and non-induction regimens in Etamivan terms of patient or graft survival. Several randomized, multicenter studies report that the efficacy of rATG induction therapy is generally no different from that of basiliximab or low-dose daclizumab (anti-IL-2R monoclonal antibodies [mAbs], described below) with regard to the incidence of BPAR, graft loss or death at 6 and 12 months post-transplantation, in the context of renal transplant recipients receiving triple immunosuppressive maintenance therapy [9,18,19]. These trials, however, were not powered to show overall superiority of one agent over the other , but instead were focused on safety parameters  at different dosage levels . More robust studies are needed that are designed to Rabbit Polyclonal to CD70 specifically evaluate the efficacy of rATG relative to IL-2R mAbs, in order to definitively establish the use of rATG with respect to these monoclonal agents. Minimized maintenance immunosuppression The considerable morbidity concerns associated with long-term corticosteroid therapy have directed clinical studies to explore minimization of steroid use in maintenance immunosuppression. Limited data in adult and pediatric renal transplant recipients indicate that effective immunosuppression may be achieved with rATG in combination with steroid-free immunosuppressive therapy or with those using early withdrawal of steroids [20C22]. Longer-term, prospective data with larger patient numbers are needed to fully assess the efficacy of such regimens. These studies do illustrate, however, that rATG cannot be regarded as a tolerance-inducing therapy at present, but more as an immunosuppression-reducing agent; chronic maintenance therapy is still needed despite the lymphocyte-depleting effects of rATG. Polyclonal effects Polyclonal antibodies such as rATG have a nonspecific immunosuppressive action, which, although it results in profound lymphocyte depletion, can also lead to significant, undesirable side effects. These may include serum sickness (influenza-like symptoms due to immune complex deposition after foreign protein administration), neutralizing anti-rabbit (host response to nonhuman proteins), anti-idiotype antibody formation (antibody generation against the complementarity determining region), leukopenia, thrombocytopenia, gastrointestinal disorders and cytokine-release syndrome (due to mass release of Etamivan cytokines after opsonization and destruction of mature T cells). These adverse effects present substantial comorbidity for transplant recipients, particularly as clinical data are yet to provide sound evidence of prolonged graft or patient survival with the use of rATG as an induction agent. Susceptibility to infection & malignancy A major concern with immunosuppressive therapy in solid organ transplantation is the risk of infections, and indeed.