Prospective study of microchimerism in renal allograft recipients: association between HLA-DR matching, microchimerism and acute rejection

Abstract

The presence of donor-derived hematopoietic cells in blood and various tissues of the organ recipients, termed allogeneic microchimerism, has been considered to play an essential role in establishment of organ acceptance. In this study, we prospectively determined the presence of peripheral blood microchimerism (PBM) in 20 male-to-female renal allograft recipients up to 30 months post-transplantation. Recipients were categorized according to the pattern of microchimerism into microchimeric and nonmicrochimeric groups, and then state of human leukocyte antigens (HLA) Class II (DR/DQ) matching, episodes of acute rejection, age at transplantation, renal function, and history of blood transfusion were compared. DNA was extracted from donor, pre-transplant, and post-transplant (1 wk; 1, 3, 6, 12, 18, 24, and 30 months) peripheral blood samples. We analyzed PBM using nested polymerase chain reaction (PCR) amplification specific for the SRY region of the Y chromosome with a sensitivity up to 1:1 000 000. Microchimerism was detected in 13 (65%) of 20 recipients at various intervals. The highest frequency of microchimerism was at 1 wk (55%). Among microchimeric recipients, none were positive on all post-transplant analyses. Interestingly, nonmicrochimeric cases were negative throughout the study. The three recipients with an episode of acute rejection during the first week after transplantation were all in the nonmicrochimeric group with completely mismatched HLA-DR antigens. HLA-DR incompatibility was significantly lower (t-test, p<0.05) in microchimeric cases (1.0+/-0.58) than in nonmicrochimeric ones (1.9+/-0.38). But regarding HLA-DQ and other clinical parameters mentioned above, significant difference was not observed. We propose that there is an association between HLA-DR matching, microchimerism and acute graft rejection in our recipients. Our study demonstrates that, with routine immunosuppressive protocols, higher compatibility of HLA-DR antigens facilitates microchimerism induction. Then, development of new stronger immunosuppressive protocols (including conditioning) or augmentation of chimeric state (by donor-specific bone marrow infusion), especially in completely mismatched HLA-DR renal allograft recipients, may be useful for graft acceptance.