These renal transplants were performed from the same HLA-identical donor, and subjects did not require subsequent immunosuppression (112,113)

These renal transplants were performed from the same HLA-identical donor, and subjects did not require subsequent immunosuppression (112,113). prior to lung transplantation and management of antibody formation after transplant. Finally, we review immune tolerance and the future of lung transplantation to limit the toxicities of conventional immunosuppressive therapy. equine) but are administered for 3 consecutive days following transplantation (10). Lymphocyte depletion may last as long as 6C8 months (23). One Brivudine of the major concerns regarding ATG Brivudine use is the possibility of an acute cytokine storm in response to ATG infusion. Subjects may develop non-cardiogenic pulmonary edema, chest pain and shortness of breath. Milder syndromes have also been reported including a serum sickness-like illness with diffuse rash, fever, pruritus, myalgia and arthralgia. Serum sickness may occur days to weeks after infusion. A majority of ATG-treated patients will develop anti-rabbit or anti-equine antibodies (24) which may complicate subsequent ATG dosing. Additionally, thymoglobulin is a treatment option for high grade and/or refractory acute rejection (25) thus prior exposure to ATG may theoretically complicate subsequent use though there is no available literature to support this. Alemtuzumab Alemtuzumab is a monoclonal antibody directed against the cell surface marker CD52. CD52 is expressed on the surface of B-cells, T-cells, monocytes, Brivudine macrophages, and NK cells (26). Alemtuzumab binds to this cell surface protein leading to complement-mediated cytolysis, antibody-mediated cytotoxicity and programmed cell death. Alemtuzumab is dosed at 30 mg IV prior to reperfusion or immediately following transplantation (27,28). LAMA5 Alemtuzumab has a 12-day half-life; however cell function is impaired significantly longer with monocyte, B-cell and T-cell recovery at 3, 6 and 12 months respectively (29). Given the prolonged lymphopenia associated with alemtuzumab therapy, there is significant concern regarding risk of infection and post-transplant lymphoproliferative disease (PTLD). Recent work has been limited to single center and large registry studies and the results have been heterogeneous with multiple single center studies showing no significant difference in rates of infection (27,30) or PTLD (28) between alemtuzumab and basiliximab groups, while the UNOS registry analysis demonstrated increased rates of non-CMV infection and PTLD following the use of alemtuzumab compared to either basiliximab or no induction therapy (21). IL-2 receptor antagonists IL-2 receptor antagonists are chimeric antibodies (mouse + human) directed against the alpha subunit of the CD25 cell surface protein (the IL-2 receptor). Basiliximab is currently in use within the US, while daclizumab is no longer on the market due to decreased demand. These IL-2 receptor antagonists bind to the IL-2 receptor and block IL-2 dependent signaling. T-cells rely on IL-2 signaling for proliferation and differentiation thus IL-2 receptor antagonists inhibit this process. Unlike the other induction agents however, IL-2 receptor antagonists do not lead to cell death or significant T-cell depletion. Basiliximab is dosed at 20 mg at time 0 and 4 days after transplantation based on literature demonstrating increased rates of ACR if the first dose is given post-transplantation (31) mirroring findings seen in pediatric heart transplantation (32). Basiliximab has a half-life of 7.23.2 days (Basiliximab drug insert) but may block the receptor for up to 5917 days when combined with triple drug therapy consisting of cyclosporine, prednisone and mycophenolate mofetil (Basiliximab drug insert). Basiliximab is a humanized antibody and thus not associated with the infusion reactions observed during ATG and alemtuzumab treatment. Outcomes with induction Brivudine therapy There are limited randomized controlled trials comparing no induction, ATG, alemtuzumab and basiliximab, and hence clinical practice is based.