Chimerism in peripheral blood of sensitized patients waiting for renal transplantation - Clinical implications

Background. Potential renal transplant recipients with preformed antibodies to HLA resulting from previous transplants, pregnancy, and/or transfusions are unlikely to receive an allograft. The factors contributing to the long -term maintenance of antibody titers in these individuals are still unknown , In the present study, we sought to determine whether chimerism in the blo od correlates with maintenance of HLA sensitization in highly sensitized pa tients. Methods. Qualitative analysis of chimerism in blood of sensitized patients was assessed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) to HLA-DR. PCR single-strand conformation polymorphism ( PCR-SSCP) was used to confirm the extra HLA-DR antigens detected by PCR-SSO P. Results. Fourteen of 36 patients (38.9%) were positive; for more than two H LA-DR indicative of chimerism, The presence of extra HLA-DR was confirmed b y PCR-SSCP. When patients were analyzed on the basis of their panel-reactiv e antibody (PRA) status, 10 of 15 (66.7%) were positive for chimerism in th e sensitized group, compared with only two of eight (25%) in the unsensitiz ed group. Of the five males in the sensitized group who had received a bloo d transfusion but not a transplant, three were positive for chimerism. An a ssociation was observed between chimerism and maintenance of sensitization. None of the eight normal subjects studied demonstrated chimerism. Conclusions. The results obtained with sensitized patients suggest an assoc iation between blood chimerism and maintenance of HLA sensitization. We spe culate that chimerism may lead to long-term maintenance of anti-HLA antibod y titers. This finding implies that abolition of chimerism could result in the eventual elimination of antigenic stimuli for antibody production again st HLA antigens.