Central to the humoral theory of transplantation is production of antibodies by the recipient against mismatched HLA antigens\nin the donor organ. Not all mismatches result in antibody production, however, and not all antibodies are pathogenic. Serologic\nHLA matching has been the standard for solid organ allocation algorithms in current use. Antibodies do not recognize whole\nHLA molecules but rather polymorphic residues on the surface, called epitopes, which may be shared by multiple serologic HLA\nantigens. Data are accumulating that epitope analysis may be a better way to determine organ compatibility as well as the potential\nimmunogenicity of given HLA mismatches. Determination of the pathogenicity of alloantibodies is evolving. Potential features\ninclude antibody strength (as assessed by antibody titer or, more commonly and inappropriately, mean fluorescence intensity) and\nability to fix complement (in vitro by C1q or C3d assay or by IgG subclass analysis). Technical issues with the use of solid phase\nassays are also of prime importance, such as denaturation of HLA antigens and manufacturing and laboratory variability. Questions\nand controversies remain, and here we review new relevant data.
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