Microchimerism frequency two to thirty years after cadaveric kidney transplantation

Understanding the mechanisms of unresponsiveness to allograft is crucial in order to induce long-term specific immune tolerance in organ recipients. An association between persistent microchimerism following allogeneic organ transplantation and donor-specific graft acceptance has recently been proposed. However, the frequency of chimerism and its relevance in long-lasting tolerance are still unclear. We studied 12 long-surviving (20-30 years) and eight recently grafted (2 years) cadaveric kidney transplant recipients for the systemic presence of donor alleles by using allele-specific genomic amplification of DRB1 and H-Y loci. This technique enabled the detection of a 1:4000 to 1:10,000 donor-recipient cell ratio. Among long-term tolerant recipients, microchimerism was observed in only one case in the peripheral blood and four cases in the skin. These chimeric patients did not differ from others by any clinical or immunologic parameter. In the 2-year tolerant patient group, skin chimerism was evidenced in only one patient who had simultaneously received kidney and liver transplants. No correlation was observed between the presence of chimerism and the number of HLA-DR alleles shared by donor and recipient. This low frequency of microchimerism raises doubts about a major role of chimerism in development of long-lasting specific tolerance following kidney allografting.