OUTCOMES Molecular Mechanisms Associated With Donor-Specific Microchimerism in Peripheral Blood of Brazilian Patients After Liver Transplantation M.B. Araújo, L.S. Leonardi, I.F.S.F. Boin, M.I. Leonardi, L. Meirelles, L.A. Magna, E.A. Donadi and M.H.S. Kraemer ABSTRACT A large number of studies in liver transplantation have demonstrated allogeneic micro- chimerism. The clinical and immunologic implications of this finding remain inconclusive, just as the influence of HLA mismatch and donor alloreactivity also are controversial. The present study analyzed the presence of allogeneic microchimerism in liver transplant recipients in relation to donor leukocyte kinetics and rejection episodes. The study was extended to determining the influence of immunogenetic factors in patients after liver transplantation. The presence of allogeneic microchimerism was analyzed on peripheral blood of 50 recipients. DNA extracted from the samples was subjected to typing for HLA-DRB1 and -DQB1 alleles by polymerase chain reactions using sequence-specific primers (PCR/SSP). Microchimerism was identified by nested PCR/SSP. Microchimerism was detected in 72% of patients. There was significant effect of microchimerism on rejection episodes (P = .002), while HLA mismatches did not show significance for one or two mismatches (P = .98). Allogeneic microchimerism detected in the majority of liver transplant patients was observed to be significantly associated with rejection episodes. L IVER transplantation is a definitive therapeutic modal- ity for end-stage liver diseases. The primary objective after a successful transplant is to obtain specific immuno- logic tolerance toward the organ without extensive admin- istration of immunosuppressive agents. Immediately after transplantation and reperfusion of the allogeneic organ, passenger leukocytes migrate from the graft into the recip- ient. Donor T cells exceed 10% of the total number in recipient blood after the first few days following liver transplantation. NK cells are detected in a similar propor- tion; B cells remain below 5%. 1 After 2 to 3 days, the number of donor cells decreases gradually, but they can be detected by flow cytometry at 2 to 3 weeks. By means of sensitive polymerase chain reaction (PCR) techniques, do- nor cells have been detected in recipient blood during the first months, but later become undetectable. 2 In many From the Immunogenetics Transplant Laboratory, Clinical Pa- thology Department, School of Medical Science, Campinas, Brazil. Supported by the Teaching and Research Support Foundation UNICAMP and Immunology Molecular Laboratory, Clinical Hospital of the Medical Faculty of Ribeirão Preto, Brazil. This article was financially supported by FAPESP—São Paulo State Research Foundation. Address reprint requests to Prof Dr Maria Helena Stangler Kraemer, Hospital das Clı´nicas, Laboratório de Imunogenética de Transplantes, Rua Zeferino Vaz s/n° Cidade Universitária, 13083- 970, Campinas–SP–Brazil. E-mail: kraemer@fcm.unicamp.br © 2006 by Elsevier Inc. All rights reserved. 0041-1345/06/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2006.02.058 Transplantation Proceedings, 38, 1411–1417 (2006) 1411