Antithymocyte globulin (ATG) is a powerful medication that modifies the body’s immune response. It serves as an immunosuppressive agent, which means it helps to reduce the activity of the immune system. This medication is created from antibodies derived from animals, specifically targeting certain human immune cells. Its primary role is to prevent the immune system from attacking healthy tissues or transplanted organs.
How Antithymocyte Globulin Works
ATG functions primarily by targeting and reducing the number of T lymphocytes, also known as T-cells. These white blood cells are central to immune responses. ATG’s mechanism of action involves several pathways that lead to T-cell depletion and modulation of other immune cells. It binds to various surface markers on T-cells, such as CD2, CD3, CD4, and CD8, initiating their destruction.
One significant way ATG depletes T-cells is through complement-dependent lysis. Antibodies bind to the T-cells and trigger a cascade of proteins that create holes in the cell membrane, leading to cell death. Another method is apoptosis, a process of programmed cell death, where ATG induces T-cells to self-destruct. ATG also influences other immune cells and their functions, including modulating T-cell activation, inhibiting their movement to target tissues, and interfering with their cytotoxic activities.
Where Antithymocyte Globulin is Used
ATG is used in organ transplantation to prevent the recipient’s immune system from rejecting the new organ. It can be administered as part of initial immunosuppression therapy, known as induction therapy, before or during transplantation to reduce the risk of acute rejection. If acute rejection occurs after transplantation, ATG can also treat and reverse the immune attack on the transplanted organ.
Beyond transplantation, ATG is used in treating hematological conditions like severe aplastic anemia. Aplastic anemia is a disorder where the bone marrow does not produce enough new blood cells, caused by the immune system attacking bone marrow stem cells. In these cases, ATG suppresses the immune cells responsible for this attack, allowing the bone marrow to recover and resume normal blood cell production.
Administering Antithymocyte Globulin and Managing Side Effects
ATG is typically administered intravenously, infused directly into a vein, usually in a hospital setting under close medical supervision. The first dose is often given slowly, over a minimum of 6 hours, with subsequent doses taking at least 4 hours, to minimize immediate reactions. Healthcare providers may also give other medications, such as corticosteroids, acetaminophen, or antihistamines, before the infusion to reduce the likelihood of these immediate reactions.
Patients receiving ATG are monitored for side effects during and after the infusion. One serious concern is cytokine release syndrome (CRS), which can cause symptoms like fever, chills, rapid heart rate, and shortness of breath. Other common immediate reactions include headaches, nausea, abdominal pain, and changes in blood pressure. Due to its immunosuppressive nature, ATG increases the risk of infections, including the reactivation of latent viral infections, and a long-term risk of certain malignancies like lymphoproliferative disorders. Blood tests are routinely performed to monitor blood cell counts, as ATG can temporarily lower white blood cell and platelet levels, which may require dose adjustments.
Different Forms of Antithymocyte Globulin
Antithymocyte globulin is not a single, standardized product. It exists in different forms, primarily distinguished by the animal from which the antibodies are derived. The two main types are rabbit antithymocyte globulin (rATG) and equine antithymocyte globulin (hATG). These forms can exhibit varying properties, including their potency and how long they remain active in the body.
The choice between rabbit and equine ATG depends on the specific medical condition and individual patient factors. For instance, in some cases of aplastic anemia, horse ATG has shown superior response rates compared to rabbit ATG, though overall survival rates may be comparable with successful second-line treatments. Conversely, in allogeneic stem cell transplantation, rabbit ATG has been associated with quicker platelet engraftment and shorter hospital stays in some studies. These differences require careful consideration when selecting the appropriate ATG formulation for a patient.