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Chapter 114 : Evaluation of the Humoral Response in Transplantation
Antibodies of the IgG class can damage tissues in a variety of ways, including (i) directly through complement activation, (ii) indirectly through the deposition of immune complexes, and (iii) indirectly through the recruitment of cytotoxic or inflammation-inducing cells. Very high levels of antibody result in hyperacute rejection and graft failure, an outcome that can easily be avoided by the performance of a lymphocyte crossmatch test prior to transplantation. In contrast, clear elucidation of the relevance of donor-reactive antibodies of various strengths and specificities and of antibodies that arise after transplantation has been hampered by inadequate technologies and lack of reimbursement for posttransplant monitoring of antibodies. Nonetheless, a deleterious effect of antibody specific for mismatched donor HLA antigens has been demonstrated for nearly every type of organ and tissue that has been transplanted in sufficient numbers, including hematopoietic stem cells and, possibly, composite tissues. There is overwhelming evidence indicating that anti-HLA antibodies are involved in hyperacute, acute, and chronic rejection of organs (1). In mismatched bone marrow transplants, there is a risk of immunocompetent tissues from sensitized patients producing antibody to recipient tissues as well as a risk of recipients making antidonor antibodies. In theory, antibodies specific for any antigen on transplanted tissue should be capable of damaging the transplant. The best-known antibodies that are injurious to allografts are those specific for antigens of the HLA and ABO systems. Potential deleterious effects of other antibodies are being recognized increasingly. A discussion of those is beyond the scope of this chapter, and the interested reader is directed to two excellent reviews on this topic (2, 3). The focus of this chapter will be HLA-specific antibodies, and we will use the term donor-specific antibody (DSA) to refer to antibody(ies) specific for donor HLA antigens.