Monoclonal Antibodies Administered Pre-Transplant
Immunologic barriers to solid organ transplantation are common. Improved
management of end-stage organ disease has increased the number of potential
organ recipients and produced a significant shortage of organs available for
transplant in comparison to the growing demand. Therefore, clinicians have
sought to transplant across previously contraindicated immunologic barriers.
In addition, more patients are surviving through their first transplant and are
now waiting for a subsequent transplant. Monoclonal antibodies are now being
employed prior to trans-plant to desensitize the recipient’s immune system.
Desensitization is a strategy where immunosuppres-sion is administered prior to
transplant to prevent hyperacute or early rejection in patients who are known
to have circulating antibodies against other
human
antigens. This strategy is generally reserved for patients who are “highly
sensitized” during their evaluation for transplant. Specifically, as a patient
develops end-stage organ disease, their medical and immunologic profiles are
characterized. Blood sam-ples from these potential recipients are screened for
the presence of antibodies against the major histo-compatibility complexes
(MHC) on the surface of other human cells, specifically human leukocyte
antigens (HLA). Potential recipients who have re-ceived blood products,
previous organ transplants, or have a history of pregnancy are at higher risk
for the development of antibodies against HLA. In addition, all humans have
pre-formed IgG and IgM antibodies against the major blood group antigens (A, B,
AB, and A1) (Reid, 2005). These antibodies will recognize donor tissue and
quickly destroy (hyperacute rejec-tion) the implanted organ if the tissue
contains previously recognized HLA within minutes to hours following
transplant. Therefore, it is necessary to evaluate the presence of pre-formed
circulating antibodies against HLA in the potential organ recipients. Some
centers will implement desensitiza-tion which incorporates monoclonal
antibodies prior to transplant to diminish the production of antibodies against
a new organ, allowing for transplant across this immunologic barrier.
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