Table 2 Immunosuppressive agents used in the included studies and cases
Intervention | Mechanism of action | Advantages | Disadvantages | Articles/cases |
|---|---|---|---|---|
Steroid | Multifactorial immunosuppressive | Rapid immunosuppressive effectKnown to be potent suppressor of T cell function and activity | High-dose corticosteroids increase the risk of infections, gastric ulcer, exacerbate congestive heart failure, trigger/dys-regulate diabetes | [10,11,12,13,14, 23,24,25, 27,28,29,30,31,32,33, 36, 37, 39, 44,45,46, 48, 49, 51, 52, 54,55,56,57, 59, 63, 71] (total 38) |
Antithymocyte globulin | Polyclonal antibody induces T-lymphocyte depletion via complement-dependent cell lysis | Can induce large reductions (through cell lysis) in the number of circulating T-lymphocytes | After administration the patient becomes immune-deficient for a longer period of time. Risk of anaphylactic reactions. | [16, 22, 26, 49, 56, 57, 64, 67] (total: 11) |
Mycophenolate mofetil | Inhibits the proliferation of T- and B-lymphocytes | Has a cytostatic effect on B- and T-lymphocytes | Risk of infections. Risk of reactivating hepatitis B or C, Epstein-Barr virus and Cytomegalovirus | [8, 15, 17, 21, 22, 26, 35, 54, 57, 64, 68] (total: 14) |
Infliximab | Monoclonal antibody inhibits tumor necrosis factor (TNF-alfa) | Inhibits cell signaling that induces inflammation | Risk of serious infections | [18, 39, 47, 50, 56, 57, 62, 65] (total: 8) |
Alemtuzumab | Monoclonal antibody that binds to CD52 on the surface of mature T- and B-lymphocytes, which induces their destruction through activation of the complement system | Induces rapid T-cell depletion | Risk of inducing autoimmune diseases and infections | [8] (total: 1) |
Abatacept | A fusion protein that binds CD28/CD86, which modulates the co-stimulation of T-cells so they cannot be activated | Blocks the activation of T-cells | Risk of infections, risk of inducing malignancy | (total: 2) |
Plasmapheresis | An extracorporeal therapy, which can remove immune complexes from the blood | Rapid removal of circulating immune complexes from the blood of the patient | Risk of infections | [8, 9, 17, 18, 20, 21, 34, 40, 58, 61, 65, 66] (total: 12) |
Tocilizumab | Humanized monoclonal antibody directed at the proinflammatory cytokine interleukin (IL)-6-receptor | Anti-inflammatory effect | Risk of gastrointestinal perforationRisk of infections | (total: 2) |
Immuno-globulin | Induces inactivation of autoreactive T-cells, inactivation of B-cells, regulation and antibody production. Interferes with complement activation | Has several immunosuppressive effects | Risk of acute kidney injury and thromboembolic events | [18, 34, 38, 40,41,42,43, 53, 56, 58, 60, 65, 66, 68,69,70] (total: 18) |
Rituximab | Monoclonal antibody directed towards CD20 on B-cells, binding causes death of the cell and B-cell depletion | Induces depletion of B-cells | Increased infections and rare opportunistic infections, such as PML, have been reported | (total: 2) |
Tacrolimus | Inhibits calcineurin, which is involved in the production of IL-2. IL-2 promotes the development and proliferation of T-cells | Inhibits development and proliferation of T-cells | Risk of infections, kidney and liver toxicity and blindness | (total: 2) |
Methotrexate | Antimetabolite that inhibits the enzyme dihydrofolate, which leads to a lack of tetrahydrofolate and thereby inhibits the DNA-synthesis of cells | Suppressing of the functions of T-cells | Risk of infections, pulmonary side effects and hepatotoxity | [40] (total: 1) |
Cyclophos-phamide | Cyclophosphamide is an alkylating agent with cytostatic effect. It binds the RNA and DNA of the cell, leading to the inactivation of transcription and translation | Affects both the humoral and the cellular immune response | Bone marrow suppression | (total: 2) |