Antithymocyte Globulin

• Antithymocyte Globulin (ATG) is an immunosuppressive drug made from animal antibodies.
• Its primary antithymocyte globulin mechanism involves depleting and inactivating T-lymphocytes, crucial cells in the immune response.
• Key antithymocyte globulin uses include preventing organ transplant rejection and treating severe aplastic anemia.
• Patients receiving ATG must be monitored closely for significant antithymocyte globulin side effects, such as infusion reactions, increased infection risk, and myelosuppression.

What is Antithymocyte Globulin?

Antithymocyte Globulin (ATG) is a complex mixture of polyclonal antibodies derived from horses or rabbits immunized with human thymocytes (T-lymphocytes). These antibodies target various surface proteins on human T-lymphocytes, leading to their depletion and functional impairment. This immunosuppressive action is vital in clinical settings where a robust immune response needs to be suppressed or modulated.

How Antithymocyte Globulin Works

The primary antithymocyte globulin mechanism involves its interaction with T-lymphocytes. Upon administration, ATG binds to a wide range of surface antigens on T-cells, including CD2, CD3, CD4, CD8, CD11a, CD18, CD25, CD44, CD45, CD49d, CD50, CD58, CD62L, and HLA class I molecules. This binding initiates several processes that lead to T-cell depletion and dysfunction. Mechanisms include complement-mediated lysis, antibody-dependent cell-mediated cytotoxicity, and direct induction of apoptosis (programmed cell death). The depletion of T-cells reduces the body’s ability to mount an immune response, which is crucial in preventing rejection of transplanted organs or suppressing autoimmune activity.

Clinical Uses of Antithymocyte Globulin

The potent immunosuppressive properties of ATG make it invaluable in several clinical scenarios. The main antithymocyte globulin uses are centered around conditions where immune suppression is critical for patient outcomes. In organ transplantation, ATG is frequently used both for induction therapy, to prevent acute rejection immediately after transplantation, and for the treatment of acute rejection episodes that occur despite other immunosuppressive regimens. Its ability to rapidly deplete T-cells helps to establish immune tolerance to the new organ.

Beyond transplantation, ATG is a cornerstone in the treatment of severe aplastic anemia, a rare and life-threatening bone marrow failure disorder. In this condition, the immune system mistakenly attacks and destroys the bone marrow stem cells. ATG helps to suppress this autoimmune attack, allowing the bone marrow to recover its function. It may also be considered in other autoimmune diseases where conventional therapies have failed, although these applications are less common and often off-label.

Side Effects of Antithymocyte Globulin

While highly effective, Antithymocyte Globulin is associated with a range of significant side effects due to its potent immunosuppressive nature and its animal origin. Patients receiving ATG require close monitoring to manage these adverse reactions. Common immediate antithymocyte globulin side effects include infusion-related reactions, often manifesting as fever, chills, rash, hypotension, or dyspnea, which typically occur during or shortly after the infusion. These reactions are often managed with premedication, such as corticosteroids, antihistamines, and antipyretics.

Delayed side effects are primarily related to the profound immunosuppression induced by ATG. These include a significantly increased risk of infections, encompassing bacterial, viral (e.g., cytomegalovirus, Epstein-Barr virus), and fungal pathogens. Patients are also at a higher risk for developing lymphoproliferative disorders, including post-transplant lymphoproliferative disorder (PTLD), due to the prolonged suppression of the immune system. Myelosuppression, leading to low white blood cell counts (leukopenia), low platelet counts (thrombocytopenia), and anemia, is another common concern, necessitating regular blood count monitoring. Less commonly, serum sickness, an immune complex-mediated reaction, can occur several days to weeks after treatment.