Epitope specificity of HLA class I alloantibodies: II. Stability of cross-reactive group antibody patterns over extended time periods.

The stability of HLA alloantibodies was studied in 128 antibody-positive, potential kidney transplant recipients over an average period of 3 years. Antibody detection was performed using an anti-human globulin-complement-dependent cytotoxicity technique. In this study, the specificity of antibodies was categorized as against either private epitopes or cross-reactive group (CREG) epitope clusters. Definable antibodies were found in 94% of patients, and 89.5% of the definable antibodies had specificity for CREG clusters. Patterns of antibody reactivity were stable in most of the patients evaluated, even though the percentage of panel-reactive antibody (PRA) often demonstrated considerable fluctuations. Of the 220 definable private-specific or CREG cluster-specific antibodies identified in the patients, nearly 80% persisted throughout the observation period. The fluctuations in % PRA were common, but usually were not due to the acquisition of new HLA antibodies. Most fluctuations were attributable to variable detection of specificities within the same CREG cluster, possibly due to technique variation or changes in antibody avidity or titer or in cell panel composition. This study demonstrates that patterns of antibody specificity are remarkably stable in this patient population, even though PRA values fluctuated. This study further suggests that HLA antibody specificity analysis is a more useful clinical parameter of lymphocytotoxicity testing than simple reporting of % PRA when identifying potential donors for individual patients.