Lymphocyte-depleting agents

Attempts to minimize TAC-induced renal dysfunction by TAC switch to sirolimus [419, 744, 745] or use of low-dose maintenance TAC therapy associated with lymphocyte depleting agents, mycophenolate mofetil or sirolimus have been successfully achieved [746-750]. However, the association of TAC and sirolimus does not seem to be problem-free. Severe acute kidney injury in renal transplant recipients and thrombotic microangiopathy in intestinal transplant have been associated to combined use of TAC and sirolimus [751, 752], renal function improved in renal transplant recipients after conversion from TAC/ sirolimus to TAC/MMF therapy [753] and TAC/sirolimus combination was associated to worst renal allograft survival than TAC/MMF im-... 

Ellis D, Shapiro R, Moritz M, Vats A, Basu A, Tan FI, Kayler L, Janosky J, Starzl TE. Renal transplantation in children managed with lymphocyte depleting agents and low-dose maintenace tacrolimus monotherapy.Transplantation 2007 83 1563-1570. 

Mitochondria-associated toxicities, such as pancreatitis, are frequently demonstrated in HlV/HCV-coinfected individuals, and may significantly influence treatment options (de Mendoza and Soriano 2005). Yet, no cell culture or animal models have been developed to predict nucleoside-induced pancreatitis. Nevertheless, an association of HCV replication and mitochondrial DNA depletion in primary human lymphocytes obtained from HIV/HCV-coinfected individuals under concomitant administration of HCV and HIV medications was demonstrated by de Mendoza and coworkers (de Mendoza et al. 2007). They claimed that the use of HCV medication together with certain antiretroviral agents seemed to enhance mitochondrial damage due to a synergistic deleterious interaction between the anti-HCV and anti-HIV drugs. In contrast, an improvement in mitochondrial content with effective... 

HIV-1 is the etiologic agent responsible for AIDS, a syndrome characterized by depletion of CD4+ T-lymphocytes and collapse of the immune system. People with AIDS are prone to opportunistic infections easily defended against by a normal immune system. Generally, it takes several years, post-infection, to progress to AIDS. 

NK cells, monocytes, macrophages, and a small population of granulocytes. Currently, alemtuzumab is approved for the treatment of -cell chronic lymphocytic leukemia in patients who have been treated with alkylating agents and have failed fludarabine therapy. Alemtuzumab appears to deplete leukemic and normal cells by direct antibody-dependent lysis. Patients receiving this antibody become lymphopenic and may also become neutropenic, anemic, and thrombocytopenic. As a result patients should be closely monitored for opportunistic infections and hematologic toxicity. 

Alemtuzumab (campath-lH) is a humanized monoclonal antibody specific for the CDw52 antigen, present on cell membranes of lymphocytes and monocytes. It has been used for treatment of patients with rheumatoid arthritis and vasculitis, is being investigated for the treatment of chronic lymphocytic leukemia, and has been used to deplete circulating lymphocytes in patients with multiple sclerosis (1). In 2001, alemtuzumab was approved in Europe for the treatment of chronic B cell lymphocytic leukemia that had been treated previously with alkylating agents and was refractory to fludarabine (2). It has also been used for induction of immunosuppression/tolerance in liver transplant recipients (3,4) and kidney/pancreas transplant recipients (5). 

Most of the NAD turnover in non-dividing human lymphocytes is attributable to ADP-ribosylation reactions. A rise in ADPRT activity, in response to increasing DNA strand breaks, causes NAD to be consumed without a compensatory rise in NAD synthesis. Thus, excessive poly(ADP-ribose) polymerase activity, relative to NAD synthetic capacity, provides a common mechanism by which quiescent lymphocytes suffer lethal NAD depletion following exposure to agents that damage DNA. The deaminase-resistant congener CdA produces a prompt reduction of the leucocytosis in... 

---