High panel reactive antibody against cross-reactive group antigens as a contraindication to renal allotransplantation

Preformed circulating cytotoxic IgG anti-HLA alloantibodies induced by previous failed grafts, blood transfusion, or pregnancy are a contraindication to allotransplantation and result in hyperacute rejection. These persistent, highly cytotoxic panel reactive antibodies (PRAs) may be specific for epitopes that are shared among HLA antigens known as cross-reactive groups (CREGs). The present investigation includes 24 subjects awaiting renal transplants with flow cytometric PRAs >30%. Eighty-seven percent of the patients developed alloantibodies specific for the mismatched antigens of previous failed grafts. The complement-dependent cytotoxicity test revealed that A1 and A2 antigens were highly immunogenic, whereas A23, B35, and B7 were less so. All patients who formed anti-A1 and anti-A2 also had developed alloantibodies specific for other antigens of the 1C and 2C CREGs, respectively. The presence of anti-class II HLA alloantibodies led to poor graft survival, i.e., a maximum of 2 years.