Development of microchimerism in pediatric patients after living-related liver transplantation

Microchimerism has been suggested to play an important role in the long-term acceptance of allogeneic organ grafts by transplant patients and for the maintenance of a state of donor-specific low responsiveness. In order to elucidate the kinetics of the development of chimerism we have performed a follow-up analysis in 10 pediatric patients with living-related liver transplantation (LRLTx). Blood samples obtained during the first 6 months and at 18 months post-transplant and skin biopsies taken at one month were analysed for the presence of donor cells by PCR using donor-specific HLA-DRB1 primer pairs or primers for a Y chromosome-specific sequence. Furthermore 13 long-term patients more than 2 yr after LRLTx were studied at two different time points. In the follow-up studies donor cells could be demonstrated in the blood of all patients immediately after transplantation. After a gradual decline all patients became chimerism-negative for several weeks or months. At 6 months, however, in five of eight patients tested and at 18 months in six of nine patients donor cells had reappeared. This biphasic pattern in the development of chimerism is proposed to reflect the occurrence of different donor-derived cell populations in the recipient. The population giving rise to the first wave of chimerism probably represents matured cells with a limited lifespan which are released from the graft into the circulation of the recipient during the first weeks after transplantation. The population of cells occurring with the second wave of chimerism is likely to have been generated by donor-derived cells with stem cell potential located either in the graft or in the hematopoetic organs of the recipient after emigration from the graft. This model may be able to explain fluctuations in the incidence and degree of microchimerism described in other patient populations during the first year post-transplant. Of the 13 long-term patients, chimerism could be demonstrated in 11. In seven patients it was detected in both blood and skin, in three patients the results obtained for blood and skin were discordant. In one patient only blood was analysed. It is not clear whether the negative results really reflected the absence of chimerism or whether the number of donor cells was below the level of detectability.