What is the role of polyclonal antibodies (antithymocyte globulins) in immunosuppression after solid organ transplantation?

Updated: Jan 04, 2016
  • Author: Bethany Pellegrino, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Answer

Polyclonal antibodies (antithymocyte globulins)

Antithymocyte globulins have been used commonly for induction immunosuppression and treatment of acute rejection in solid organ transplantation. These agents are derived by injecting animals (rabbit or horse) with human lymphoid cells, then harvesting and purifying the resultant antibody. Polyclonal antibodies induce the complement lysis of lymphocytes and uptake of lymphocytes by the reticuloendothelial system and mask the lymphoid cell-surface receptors. Preparations include horse antithymocyte globulin (Atgam) and rabbit antithymocyte globulin (Thymoglobulin, ATG). Although ATG is the favored agent, equine preparations have historically been used.

Most regimens involve 5-7 days of intravenous administration of thymoglobulin for induction immunosuppression or treatment of corticosteroid-resistant rejection or antibody-mediated rejection.

Thymoglobulin is a polyclonal antibody that has been used in the field of transplantation over the last 4 decades. Thymoglobulin's lack of nephrotoxic properties (unlike calcineurin inhibitors) may potentiate it to be a beneficial induction therapy during the early days following transplantation. In conjunction with inhibitors of terminal complement activation, it has been shown to be beneficial in cross-match–positive transplantation.

Thymoglobulin possibly provides better protection against acute rejection and improves patient and graft survival but may result in more CMV infection and posttransplantation malignancy. Thymoglobulin causes leukocyte depletion with a greater delay to recover. Of special importance is adding antiviral therapy to the treatment regimen of patients who receive antithymocyte globulins as induction therapy.

As polyclonal agents are xenogenic proteins, adverse effects include fever and chills. Other adverse effects are thrombocytopenia, leukopenia, hemolysis, respiratory distress, serum sickness, and anaphylaxis. Thymoglobulin rarely causes adult respiratory distress syndrome. Some adverse effects are ameliorated with steroids, acetaminophen, and diphenhydramine. A high average dose of antithymocyte immunoglobulin has been associated with an increased risk of non-Hodgkin lymphoma.

Thymoglobulin administration is associated with coagulopathy. Using an international normalized ratio screening protocol and an aggressive transfusion protocol, bleeding complications associated with coagulopathy can be avoided in this higher-risk group.


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