Pretransplantation fetal-maternal microchimerism in pediatric liver transplantation from mother (original) (raw)
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Transplantation Proceedings, 2004
Migration of donor-derived cells to recipient tissues after liver transplantation has been suggested as a mechanism to induce and maintain allograft tolerance, although important issues remain including acute rejection posttransplantation mortality, and complications related to immunosuppressive therapy. We therefore examined the relation of rejection to chimerism based upon recipient and donor mismatch of HLA-DRB1 and -DQB1 alleles. Laboratory analysis of peripheral blood was performed before and 10 days to 16 months after liver transplantation in 32 recipients, using ganglion or spleen cell samples of respective donors. DNA was extracted for HLA-DRB1 and DQB1 allele typing using polymerase chain reactions with sequencespecific primers (PCR-SSP). Microchimerism was analyzed through nested PCR. Our results confirmed that patients with one or two mismatched HLA-DRB1 and-DQB1 alleles showed microchimerism and no rejection (P Ͻ .05). Microchimerism was present in 71.88% of the patients, and a significant association of rejection P Ͻ .05 was found when microchimerism was correlated to graft rejection. These results suggest that the presence of microchimerism may be associated with acceptance, tolerance and survival of the allograft.
Transplantation Proceedings, 2006
A large number of studies in liver transplantation have demonstrated allogeneic microchimerism. 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 ϭ .002), while HLA mismatches did not show significance for one or two mismatches (P ϭ .98). Allogeneic microchimerism detected in the majority of liver transplant patients was observed to be significantly associated with rejection episodes.
Hepatology, 1997
Donor-type microchimerism, the presence of a minority However, consensus has not emerged regarding the necessity for donor cells to remain in circulation or tissues distal population of donor-derived haematopoietic cells following solid organ transplantation, has been postulated as a mecha-to the transplanted organ before tolerance can emerge, and the biological relevance of donor microchimerism in allograft nism for induction of donor-specific graft tolerance. The stability, frequency, and relevance of microchimerism with re-recipients remains controversial. 9,10 This has been further complicated by case reports documenting donor microchi-spect to long-term outcome, however, remains uncertain. Using a polymerase chain reaction (PCR)-based method of merism in association with graft rejection. 11 Further studies have failed to document donor microchimerism following microsatellite analysis of highly polymorphic short tandem repeat sequences (STRs) to detect donor-type cells, DNA from orthotopic liver transplantation (OLT) despite infusion of donor bone marrow. 12 As a result, the biological significance 11 patients was analyzed prospectively at specific time points for 12 months following liver transplantation, and from a of donor microchimerism in allograft recipients has been questioned. Much of the published data has depended on further six patients retrospectively 2 years after liver transplantation. Using a panel of STRs, transient peripheral blood the use of highly sensitive polymerase chain reaction (PCR)based technologies to detect donor cells following liver trans-donor microchimerism was detected in 2 of 11 patients at a single time-point following transplantation, but persistent plantation, in particular, nested PCR, which can detect donor or foreign cell populations to a level of one cell in 10 5-10 6 evidence of donor-derived cells was not observed during the study period. Analysis of DNA extracted from skin and duode-cells. The clinical significance of a detection rate at this level is unclear. num in two patients likewise failed to show donor-type cells at these sites. None of the six patients in the retrospective Hematopoietic chimerism is the term originally used to describe the characteristics of cellular repopulation of the arm showed donor microchimerism, resulting in an overall detection rate of 1.58%. These results suggest that donor host bone marrow cavity with hematopoietic stem cells during allogeneic stem cell transplantation (SCT) following mar-microchimerism following liver transplantation is an infrequent event, and that the generation of graft tolerance is inde-row ablative chemotherapy. We have previously developed a PCR-based strategy to evaluate bone marrow repopulation pendent of microchimerism. (HEPATOLOGY 1997;26:848-852.) following allogeneic SC. 13 Donor and recipient cells are distinguished by using PCR of short tandem repeats (STR-PCR). Transplantation tolerance, the long-term acceptance of STRs are di-, tri-, or tetra-nucleotide repeat sequences that grafted tissue in the absence of continuous immunosuppresare spread randomly throughout the human genome. Polysion, remains an elusive ideal goal in human transplantation. morphic variation is shown by differences in the number of Proposed mechanisms influencing graft acceptance include repeat sequences between individuals. Thus, STR-PCR can peripheral anergy, clonal deletion of donor-reactive cytotoxic be used to distinguish donor, mixed, or recipient chimerism T cells, and suppression of alloreactive clonotype. 1,2 In recent following allogeneic SCT. In the current study, this approach years, reports of minor percentages of donor-derived denwas used to determine the emergence, stability, and clinical dritic or hematopoietic cells detected in various tissues in relevance of donor microchimerism prospectively in a serial long-term kidney, 3 liver, 4 and heart recipient, 5 referred to as fashion following liver transplantation, and retrospectively ''donor microchimerism'' resulted in a novel theory to eluciin a second group of patients who had undergone transdate the generation of graft tolerance following transplantaplantation two years previously. tion. Many studies have reported donor microchimerism PATIENTS AND METHODS years following solid organ transplantation and have highlighted the importance of longlived donor-derived cells in Patients. Eleven patients were enrolled in the study for 12 months generating long-term graft acceptance. 6-8 from the time of liver transplantation and followed prospectively, while six patients were studied at 2 years following OLT. Transplantation was performed for a range of diseases including primary biliary cirrhosis (n Å 4), autoimmune hepatitis (n Å 4), primary Abbreviations: OLT, orthotopic liver transplantation; PCR, polymerase chain reacsclerosing cholangitis (n Å 2), cryptogenic cirrhosis (n Å 3), fulmition; SCT, stem cell transplantation; STR, short tandem repeats. nant hepatic failure (n Å 3), and alcohol-related cirrhosis (n Å 1).
Transplant Immunology, 2009
After liver transplantation, migration of donor-derived hematopoietic cells to recipient can be detected in pheripheral blood. This state is termed microchimerism. The aim of this study was to investigate prospectively the presence of allogeneic microchimerism, the occurrence of acute cellular rejection and the level of immunosuppression in transplanted patients. Microchimerism occurrence between 10 days and 12 months after liver transplantation was analyzed in 47 patients aged between 15 and 65 by a two-stage nested PCR/SSP technique to detect donor MHC HLA-DR gene specifically. A pre-transplant blood sample was colleted from each patient to serve as individual negative control. Microchimerism was demonstrated in 32 (68%) of the 47 patients; of these, only 10 patients (31.2%) presented rejection. Early microchimerism was observed in 25 patients (78.12%) and late microchimerism in 7 patients (21.8%). Among the patients with microchimerism, 14 were given CyA and 18 were given FK506. In the group without microchimerism, 12 patients were given CyA and 03 were given FK506. There was a significant association between the presence of microchimerism and the absence of rejection (p = 0.02) and also between microchimerism and the type of immunosuppression used. Our data indicate that microchimerism and probably differentiation of donorderived leukocytes can have relevant immunologic effects both in terms of sensitization of recipient and in terms of immunomodulation toward tolerance induction.
Transplantation Proceedings, 2006
Background. We sought to determine the extent and time course of recipient-derived chimerism after transplantation and the relationship with acute rejection episodes (ARE) and HLA typing in hepatic allograft patients. Patients and Methods. We studied 18 needle liver biopsy specimens from patients who had undergone orthotopic liver transplantation. Fluorescent in situ hybridization (FISH) analysis for X and Y chromosomes was performed in all cases with a sex mismatch. To evaluate the HLA matching, we used serological and polymerase chain reaction (PCR) methodology.
Pediatric Research, 2004
For investigating the possible influence of maternal-fetal HLA compatibility on maternal microchimerism, DNA samples from blood of 120 maternal-fetal pairs were genotyped at two polymorphic loci: glutathione-S-transferase M1 (GSTM1) and angiotensin-converting enzyme (ACE). Informative pairs (mother heterozygous/fetus homozygous at one of the two loci) were then tested by quantitative real-time PCR for the noninherited maternal allele(s) and genotyped at the HLA-A, B, and C class I loci and/or at the DRB1 and/or DQB1 class II loci. Small numbers of maternal cells were detected in the circulation of 16 of the 30 informative second-and third-trimester fetuses. Comparison with HLA data suggested an association between micro-chimerism and maternal compatibility at the class II DRB1 and/or DQB1 HLA loci and with the maternal HLA-DQB1*0301 allele. There was no relationship between maternal microchimerism and maternal-fetal HLA compatibility at other HLA loci or with gestational age, fetal anomalies, or red cell or platelet isoimmunity. Abbreviations KIR, killer inhibitory receptor NIMA, non-inherited maternal allele NK cell, natural killer cell QPCR, quantitative PCR
Urologia Internationalis, 2020
Introduction: Microchimerism (MC) is the presence of a small amount of foreign cells or DNA within a person’s circulation or tissues. It has been identified also in recipients of solid organ transplants where it seems to be critical for the development and maintenance of immunological tolerance. Nevertheless, natural and/or iatrogenic MC can be acquired prior to transplantation, through pregnancy and/or blood transfusion. Objective: The aim of this study was to detect the presence of MC in women after renal transplantation from male cadaveric donors and its relationship with graft outcomes. Methods: We studied by qPCR the presence of the DYS14 gene sequence of the Y chromosome in 12 females who received a kidney graft from a male donor before transplantation (T0), after 15 days (T1) and 1 year of transplantation (T2). We found the sequence in all recipients after renal transplantation. Results: All the women were negative for this sequence prior to transplantation (T0). Mean (SD) Y-...
Association of donor-specific microchimerism with graft dysfunction in kidney transplant patients
Transplant Immunology, 2012
The biological significance of donor-specific microchimerism (DSM) in solid organ transplantation is unresolved. It has been reported both as a favourable feature, which may facilitate induction and maintenance of tolerance, and as a sign of graft-vs-host disease. Here, we applied a quantitative real-time PCR assay (qRT-PCR) to a selected series of kidney transplant recipients to measure the level of microchimerism in relation to allograft function and survival. DSM level was assessed by scoring the HLA-DRB1 locus in 54 patients (42 males, 12 females) with more than 2 years of follow-up after transplantation; 38 patients were considered to have stable renal function (SRF) and 16 had allograft dysfunction (AD). Among patients with AD, 12 (75%) showed detectable level of microchimerism, compared to 11 (29%) SRF patients (Odds Ratio 7.36, 95% CI 1.7-35.2; p b 0.01). In addition, AD patients showed a higher mean donor genome equivalents (6.5× 10 − 5 vs. 2.4 × 10 − 5 ; pb 0.001). SRF patients were re-evaluated two years later; 2 out of 27 DSM negative vs. 2 out of 11 DSM positive had lost their transplanted organ. In conclusion, qRT-PCR applied to peripheral blood shows significant association between DSM and allograft dysfunction in kidney transplant patients.