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Organ Transplantation

Graft Rejection
    Cellular Mechanisms
    Molecular Mechanisms

Immunsuppressive Agents
    Corticosteroids
    Calcineurine Inhibitors
    Antiproliferative Agents
    Monoclonal Antibodies
    Polyclonal Antibodies
    Side Effects       

Immunotherapy
    Inductive Therapy
    Maintenance Therapy
    Episodic Treatment

Current Areas of Research
    New Drugs
    Drug Efficacy
    Alternative Therapies
        Tolerance
        Tissue Engineering
        Xenotransplantation

Glossary of Terms
References

SIDE EFFECTS

It is obvious from the table below that there are numerous side effects associated with immunosuppressant drugs. Among the most significant of these side effects are opportunistic infections and transplant-related malignancies. Many of these side effects are due in part to the weakened immune system of transplant recipients. Because of the high amount of redundancy in immune cells, immunosuppressants, which aim to decrease immunologic rejection of the transplant, inadvertently handicap the ability of the immune system as a whole. The immune system therefore has a decreased capacity to protect the individual from microorganisms and cancerous cells. Other side effects are caused by unintended drug interactions with the body. These side effects make immunosuppression difficult for the patient, and significantly affect quality of life, as immunosuppressant therapy is often life-long.

Transplant related malignancies are one of the most substantial side effects related to immunosuppressive therapy.

The overall extent of side effects due to immunosuppressants serves to remind us that there is still a lot lacking in immunosuppressants. While they become more and more effective in preventing transplant rejection, research should aim at creating immunosuppressants that are increasingly precise for transplant-specific immune cells. This would allow individuals to get rid of rejection-initiating lymphocytes, while not affecting the immune system as a whole. Current research with monoclonal and polyclonal antibodies seek to meet these aims, but new immunosuppressive approaches give rise to unexpected complications. For example, the HAMA (human anti-Murine Antibody) reaction has accompanied introduction to many of the antibodies available. In this reaction, the human body detects the murine (mouse) components of the antibodies and creates anti-mouse immunoglobulins specific for the constant region of the antibody. This results in the patient's immune system clearing the potential treatment from circulation, thus rendering it ineffective. The HAMA reaction develops within 10-14 days of treatment (other therapy may delay onset of the HAMA reaction), and comes with its share of side effects. Circumvention of this complication includes humanizing (also referred to as chimerizing) the antibody by replacing these trouble constant regions in favor of more acceptable human regions. This results in noticeable better results, as can be seen from the progression from 70%/30% human:murine drug Muromonab-CD3 to the experimental 90%/10% human:murine drugs Basiliximab and Daclizumab (both currently in clinical trials).

Another resolution would be to step away from immunosuppressants entirely, whether through induction of tolerance, the use of autographic transplants derived through tissue engineering, stem cell therapy, or genetically engineered xenotransplants. These options, which will be discussed briefly in another section of the website, are not currently available, but are possible aspirations for the future and are being heavily researched.