Profiling class II HLA alloantibodies in transplant patient sera (P2222)

Abstract Allogeneic immunizing events including pregnancy, blood transfusion, and transplantation promote strong antibody responses to HLA. Such anti-HLA antibodies preclude organ transplantation, foster hyperacute rejection, and contribute to chronic transplant failure. Diagnostic antibody-screening assays can detect alloreactive antibodies and determine their HLA specificity, yet a number of key antibody attributes remain unexplored. The goal here was to provide the first detailed profile of antibodies directed to allogeneic HLA. Methodologically, sixteen sensitized patients were identified with alloantibodies to HLA-DR11, antibodies reactive with this class II HLA antigen were purified using a novel immunoaffinity column constructed with milligram quantities of native DR11, and these purified DR11 specific antibodies were categorized. Results show that allogeneic antibodies to DR11 were found in the serum at a median concentration of 2.3ug/ml and consisted of the IgM, IgG, IgA, and IgE isotypes. IgG2, IgM, and IgE were elevated while IgG1 was decreased in sensitized patients and, in most patients, these antibodies fixed complement. In conclusion, we show that HLA alloantibody responses are consistently comprised of multiple isotypes, that these alloantibodies reach an appreciable serum concentration, and that these alloantibodies fix complement.