Antilymphocyte/antithymocyte globulin

Both globulins exert their effect by depletion of circulating lymphocytes either by complement-dependent lysis or by phagocytosis after opsonization. However, antilymphocyte globulin (ALG) and antithymocyte globulin (ATG) are nonhuman polyclonal antibodies. To prevent sensitization application is restricted to a time period of several days only. 

Therapy, when replacement of the marrow by allogeneic haematopoietic stem cell transplantation is not possible, comprises 500 mg of methylpred-nisolone by 8 hour intravenous infusion repeated for five consecutive days. Concurrently 15 mg/kg of antilymphocyte or antithymocyte globulin is given... 

ADA Adenosine deaminase ALG Antilymphocyte globulin APC Antigen-presenting cell ATG Antithymocyte globulin CD Cluster of differentiation CSF Colony-stimulating factor CTL Cytotoxic T lymphocyte DC Dendritic cell... 

Antisera directed against lymphocytes have been prepared sporadically for over 100 years. With the advent of human organ transplantation as a therapeutic option, heterologous antilymphocyte globulin (ALG) took on new importance. ALG and antithymocyte globulin (ATG) are now in clinical use in many medical centers, especially in transplantation programs. The antiserum is usually obtained by immunization of large animals such as horses or sheep with human lymphoid cells. 

Immunosuppression is used in patients who are not candidates for bone marrow transplantation due to age or to the lack of a donor (up to 70%). Horse antithymocyte globulin (ATG) or rabbit antilymphocyte globulin (ALG) induce haematological responses (transfusion-independence and freedom from infection) in 40-50%. The addition of ciclosporin to ATG or ALG improves response rates to 70-80% and survival rates in responders to 90%. Adverse effects of ATG and ALG include anaphylaxis, exacerbation of cytopenias and serum sickness. Ciclosporin is nephrotoxic. In refractory patients G-CSF and erythropoetin can improve blood counts, as can androgens in some patients. 

The risk of reactions to antilymphocyte globulin is increased in patients with autoimmune disease (126). Fever and chills, sometimes with extreme hyperpyrexia, nausea and vomiting, urticaria, and reduced platelet and granulocyte counts were reported after the administration of horse antithymocyte globulin. 

Induction therapy with polyclonal and monoclonal antibodies (mAbs) has been an important component of inunu-nosupression when the beneficial effect of antilymphocyte globulin (ALG) in the prophylaxis of rejection in renal transplant recipients was demonstrated. Over the past 40 years, several polycolonal antilymphocyte preparations have been used in renal transplantation however, only two preparations are currently FDA approved lymphocyte immune globulin (ATGAM) and antithymocyte globulin (Thymoglobulin). 

Many different types of immunosuppressants can be used to prevent or control rejection. Most of them, including steroids, suppress the entire immune system (Merck 2003). Antilymphocyte globulin, antithymocyte globulin, and monoclonal antibodies suppress only specific parts of the immune system. Immunosuppressants must be taken for an indefinite period. High doses are usually necessary for the first few weeks, and after that smaller doses can usually prevent rejection (Stark et al. 2002 Villard 2006). 

Young N, Speck B. Antithymocyte and antilymphocyte globulins CUnical trials and mecUanism of action. In Young S, et al, eds. Aplastic Anemia. Stem Cell Biology and Advances in Treatment. New York, AlanRLiss, 1984 221-226. 

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