The Role of Monoclonal Antibody in Organ Transplant
Monoclonal antibodies are used in transplantation in order to prevent the host immune recognition of the donor tissue. Allograft tissue is impaired to the host immune response by two ways namely: antibody-mediated rejection and cellular-mediated rejection. Pre-transplant screening the antibodies against the donor tissue has largely reduced the severity and incidence of antibody-mediated rejection. However, cell destruction using monoclonal technology to produce these antibodies (example, rituximab) prior to the transplant has become an alternative for recipients with preformed alloantibodies. Therefore, preventing and treating cellular-mediated rejection is the primary focus of maintaining immunosuppression and the logical use of monoclonal antibodies during the early post-transplant period.
Monoclonal Antibody Administered Before Transplant
Solid organ transplantation is subjected to immunologic barriers. Better management of the end-stage organ disease has significantly increased the number of potential organ recipients and has produced shortage of organs that are available for transplant when compared to the growing demand. Today, clinicians are beginning to opt for transplant across the previous contraindicated immunologic barrier. Further, more patients have begun to survive through their first organ transplant and wait for a subsequent transplant.
Today, monoclonal antibodies are employed prior to the transplant to desensitize the immune system of the recipient. In order to prevent early rejection or hyperacute in patients whose circulating antibodies work against other human antigens, immunosuppression is administered prior to the transplant. This strategy is called desensitization and is reserved for "highly sensitized" patients during their transplant evaluation. This is specific when a patient develops an end-state organ disease; their immunologic and medical profiles are characterized.
Blood samples collected from potential patients are then screened for antibodies against major histocompatibility complexes (MHC) found on the human cell surface, specifically the human leukocyte antigens (HLA). Potential recipients who have a history of pregnancy risk, or have received blood products, or had previous organ transplants for antibodies development against HLA. Further, all humans have pre-formed IgM and IgG antibodies against major blood-group antigens including A, AB, A1, and B. These antibodies recognize the donor tissue and destroy the implanted organ if the donor tissue contains HLAs that are previously recognized within minutes to hours following the transplant.
Therefore, in a potential organ recipient, it is necessary and important to evaluate the pre-formed circulating antibodies against HLA. Some centers tend to implement the desensitization strategy incorporating monoclonal antibodies prior to the transplant in order to diminish antibodies production against a new organ, allowing transplant to occur across this immunologic barrier.
Monoclonal Antibody Administered During Transplant
Today, maintenance immunosuppression is aimed at several targets within the immune system to hinder the propagation of signal-transduction pathway. Though the available agents are effective, they are associated with significant patients and allograft adverse effects that are associated with prolonged exposure. A cardiovascular event is the leading cause of death in non-cardiac transplant recipients. Cardiovascular event is associated with long-term corticosteroid exposure. Further, the administration of calceneurin inhibitors such as tacrolimus and cyclosporine is linked with chronic and acute kidney dysfunction that leads to kidney transplant or hemodialysis.
Monoclonal antibodies, at time of transplant, are used to reduce the requirement for corticosteroids and allow a delay or reduced the amount of calcineurin inhibitor used. Determining the immunologic risk of the solid organ transplant recipient during the time of transplant is critical in determining the monoclonal antibody that is to be used to reduce graft loss and early acute rejection. Muromanab and Interleukin-2 Receptor Antagonists are two commonly used agents in solid organ transplant.
For example, liver and heart transplant recipients reportedly lose volumes of blood during transplant, therefore intraoperative administration is not recommended since most is lost during surgery. Monoclonal antibodies are removed by plasma exchange procedure (plasmapheresis) which is performed during preoperative period.
Monoclonal Antibody Administered After Transplant
Monoclonal antibodies administered following transplant are used in treating allograft rejection. Administering these agents is done for severe allograft rejection. The humoral immune system, under normal homeostatic conditions, gives immediate control over infectious pathogens via antibody secretion.
Cell-mediated immunity, apart from fighting infections, keeps an effective watch against the production of mutant cells that are capable of oncogenesis. Interrupting either of these immune systems via the use of monoclonal antibodies puts these patients at high risk for malignancy and infection. Therefore, careful post-administration assessment of post-transplant malignancy and infection is necessary.
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