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Immune monitoring of anti-thymocyte globulin (ATG) treatment in transplant patients

Lookup NU author(s): Dr Brian Shenton, Professor Derek Manas, Professor John Dark, David Talbot, Alison Bell


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Over the past few years there has been an increasing array of monoclonal antibodies directed against immunocompetent lymphocytes available for use in the prevention and treatment of rejection in solid organ transplantation. Despite this there has been a continued and expanding use of polyclonal anti-T cell globulins in the management of cardiac, lung and renal transplants in many centres. As with all immunosuppressive drugs over and under-immunosuppression remains a major problem. A number of different methods have been described for monitoring anti-thymocyte globulin (ATG) therapy in transplant patients. These include: monitoring serum IgG levels, the E- rosette assay; flow cytometry and monoclonal antibodies. The measurement of serum IgG levels of the host animal (rabbit or horse) has been shown not to correlate with the presence of acute rejection episodes. The E-rosette assay has been found to be extremely time consuming and unreliable. With flow cytometric techniques, monoclonal antibodies directed against the T lymphocytes have been used to monitor ATG therapy and this has allowed the adjustment of the ATG administered to each individual patient. In patients receiving, renal, cardiac, lung or heart lung transplants we have developed flow cytometric assays to monitor ATG therapy on a daily basis with adjustment of the dosage of ATG administered according to this result. We have progressed from a dual platform assay where the T-cell percent from flow cytometry is combined with the lymphocyte count determined from a Haematology Cell Analyser to a single platform flow cytometric assay using commercially available polyfluorescent beads of two different types. An increasing problem with transplant patients is that ATG once given may induce antibodies against the heterologous rabbit or horse IgG. With time, a number of renal, cardiac and lung transplant patients have lost their grafts and are retransplanted. A similar situation is seen in patients who are given regular ATG therapy for the treatment of aplastic anemia. We have developed a flow cytometric duplex assay for the detection of such antibodies. This has allowed us to screen the sera of transplant patients for the presence of such antibodies before therapy is given and to suggest for that patient the most appropriate ATG to be used. The cellular and humoral assays we have developed are rapid and reproducible and are now used as routine in the clinical management of patients who are receiving or about to receive ATG therapy in transplantation. © 2001 Elsevier Science Inc. All rights reserved.

Publication metadata

Author(s): Dark JH; Shenton BK; Bell A; Manas D; Talbot D; Clark KR

Publication type: Review

Publication status: Published

Journal: Clinical and Applied Immunology Reviews

Year: 2001

Volume: 1

Issue: 6

Pages: 347-371

ISSN (print): 1529-1049

ISSN (electronic): 1878-5441


DOI: 10.1016/S1529-1049(01)00037-X