MICROCHIMERISM AND RENAL TRANSPLANTATION: DOUBT STILL PERSISTS (original) (raw)
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Transplantation Proceedings, 2006
The presence of microchimerism in the peripheral blood of solid organ graft recipients has been associated with long-term solid organ acceptance, immunologic tolerance, and less aggressive immunosuppressive therapy. Molecular biology assays are among the most sensitive methods to detect microchimerism, primarily to evaluate Y chromosome sequences in females as indirect evidence of circulating male nucleated donor cells. We screened for the presence of the SRY sequence region in peripheral blood of 13 female recipients of male kidney grafts: 5 living-related and 8 deceased grafts. 2 Only patients who received grafts from related living donors exhibited microchimerism. Five of 13 patients studied exhibited better graft outcomes, including the 4 who were positive for the SRY sequences.
Microchimerism in Peripheral Blood and Urine in Renal Transplant Recipients: Preliminary Results
Transplantation Proceedings, 2008
The role of microchimerism in peripheral blood and urine of renal transplant recipients remains a matter of debate, depending on the sensitivity of the methods used for detection. We studied 17 female renal transplant recipients who had received renal allografts from male donors. Polymerase chain reaction (PCR) was applied to blood and urine for the microsatellite markers D1S80, DYZ1, TH01, and K␣I SE33. Detection of DYZ1 that is present only on the Y chromosome was considered proof for microchimerism. No microchimerism was detected in peripheral blood, whereas it could be detected in the urine of 8/17 (48%) patients. There were no differences between patients with and without microchimerism regarding patient age, dialysis vintage, immunosuppression, time posttransplantation, and allograft function as measured using serum creatinine, creatinine clearance, and proteinuria. Two patients in each group showed chronic allograft dysfunction. These findings raise questions regarding the role of microchimerism in renal transplantation.
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.
Donor cell microchimerism in kidney transplantation: Implications for graft function
International Journal of Immunogenetics, 2020
Given the uncertainty regarding the relationship between donor cells at microchimeric levels and its influence on graft function and clinical outcome, we explored the extent and importance of donor microchimerism in kidney transplantation. Twenty patients with chronic kidney disease who had received allografts from living donors were studied. We examined peripheral whole blood samples from the recipients one month after the transplant, applying mitochondrial DNA variant‐specific polymerase chain reaction (PCR) to identify and quantify donor cells in relation to allograft function and survival during three years of follow‐up. Higher quantities of donor‐derived cell microchimerism in the peripheral blood correlated with better graft function in the early postoperative period at 1 month (R2 = .536, p = .001) and predicted improved graft function 1 year following the transplant (R2 = .430, p = .008). Furthermore, early post‐transplant quantities of donor cell microchimerism were an impo...
Histopathology, 2010
Microchimerism in renal allografts: clinicopathological associations according to the type of chimeric cells Aims: Recent studies have highlighted the presence of microchimerism in various solid allografts. The biological significance of these chimeric cells is controversial. They may be beneficial, leading to better tolerance of grafts or participating in tissue repair or, in contrast, deleterious if involved in chronic lesions. The aim was to assess the frequency and cellular nature of microchimerism in female renal grafts of male recipients by combined fluorescence in situ hybridization (FISH) for Y chromosome and immunohistochemistry and to investigate associations between intragraft microchimerism and histological lesions or allograft outcome. Methods and results: We screened 33 renal biopsy specimens, including 11 with acute T-cell-mediated rejection and nine with transplant glomerulopathy, from 22 male recipients transplanted with female kidneys by FISH and immunohistochemistry with antibodies against smooth muscle actin (mesangial cells), CD31 (endothelial cells), KL1 (epithelial cells), CD45 (leucocyte common antigen) and glomerular epithelial protein 1 (podocytes). Tubular microchimerism was detected in 71% of the patients with a mean percentage of chimeric epithelial cells of 1.4%. Glomerular microchimerism involving podocytes, mesangial and endothelial cells was present with a mean number of chimeric cells per glomerular section of, respectively, 0.6, 2.66 and 3.53. There was an association between endothelial microchimerism and a previous episode of acute T-cell-mediated rejection. Conclusions: In conclusion, microchimerism in renal grafts occurs frequently, but at a low level and affects tubular cells and all glomerular cell compartments in human renal allografts.
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-...
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.
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).