Which immunosuppressive therapies are used to treat acute rejection 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

Answer

Acute

The 3 agents used to treat acute rejection are (1) steroids, (2) antithymocyte globulin, and (3) muromonab-CD3.

  • Steroids: These agents are the mainstay of therapy for acute rejection episodes, preventing release of IL-1 by macrophages and blocking synthesis of IL-2 by helper T cells. Steroids also have anti-inflammatory properties. The typical dosage is 3-5 mg/kg/d for 3-5 days, which is then tapered to a maintenance dose. Steroids reverse 60-75% of rejection episodes.

  • Antithymocyte globulin: This agent binds all circulating T and B lymphocytes, which are then lysed or phagocytosed by the reticuloendothelial system. Antithymocyte globulin has efficacy similar to that of muromonab-CD3. It is reserved for steroid-resistant acute rejection secondary to cost, toxicity, and the development of drug antibodies.

  • Muromonab-CD3: This agent displaces the T3 molecule from antigen receptors, captures all mature T cells, and prevents alloantigen recognition. The reversal rate of first acute rejection episodes is 94%. Muromonab-CD3 is sometimes used as the first-line agent for severe vascular rejections. The development of human antimurine antibodies allows for the reappearance of CD3 T cells, which may decrease the efficacy of muromonab-CD3 and necessitate higher doses (increasing risk of infection). A second course of muromonab-CD3 may be given for recurrent rejection, although repeat treatment may be associated with complications from the development of antimouse antibodies. The success rate in recurrent episodes is approximately 40-50%.


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