Increased maternal microchimerism after open fetal surgery
ABSTRACT Maternal-fetal cellular trafficking (MFCT) during pregnancy leads to the presence of maternal cells in the fetus and of fetal cells in the mother. Since this process may be altered in cases of pregnancy complications, we asked whether open fetal surgery leads to changes in microchimerism levels. We analyzed maternal and fetal microchimerism in fetuses who underwent open fetal surgery for repair of spina bifida and compared their levels to patients who had postnatal repair and to healthy controls. We found that maternal microchimerism levels were increased in patients who had open fetal surgery compared with controls. In contrast, patients who had fetal intervention at the time of delivery did not demonstrate increased microchimerism. These results suggest that open fetal surgery may alter trafficking. Given the importance of MFCT in maternal-fetal tolerance, we discuss potential implications for the field of preterm labor and transplantation tolerance.
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ABSTRACT: The bidirectional exchange of cells, both mature and progenitor types, at the maternal-fetal interface is a common feature of mammalian reproduction. The presence of semiallogeneic cells in a host can have significant immunological effects on transplantation tolerance and rejection. Here, we review recent advances in this area. Maternal microchimerism (MMc) in blood and various organs was found to be directly correlated with noninherited maternal antigen (NIMA)-specific CD4(+) regulatory T cells (Tregs), in F(1) backcross mice. In humans, MMc induced NIMA-specific FoxP3(+) CD4 Tregs in lymph nodes and spleen of fetuses. Tolerance to NIMA(+) allografts could be predicted in mice by measuring levels of the NIMA-specific Tregs in offspring before transplantation. On the contrary, fetal microchimerism (FMc) in multiparous female mice was largely confined to CD34(+) hematopoietic stem cells (HSCs) and was associated with sensitization rather than Treg induction. The recent discovery of a 'layered' T-cell development in humans whereby fetal HSCs are more likely to produce Tregs than adult HSCs, which may explain why MMc often induces tolerance, whereas FMc tends to induce sensitization. Microchimerism may cause tolerance resulting in acceptance of an allograft bearing antigens shared by the microchimeric cells. However, microchimerism may also cause sensitization resulting in rejection. Distinguishing these effects prior to the transplant may revolutionize the field of living-related renal transplantation wherein MMc and FMc can exert a powerful influence on graft outcome.Current opinion in organ transplantation 06/2011; 16(4):359-65. DOI:10.1097/MOT.0b013e3283484b57 · 2.38 Impact Factor
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ABSTRACT: We hypothesized that transplacental leukocyte trafficking during pregnancy, which induces long-term, stable, reciprocal microchimerism in mother and child, might influence outcome of patients with acute leukemia given parental donor haploidentical hematopoietic stem cell transplantation (HSCT). We analyzed the outcome of 118 patients who received transplants for acute leukemia in 2 centers. Patients received highly T cell-depleted haploidentical grafts after myelo-ablative conditioning. Five-year event-free survival was better in patients who received transplants from the mother than from the father (50.6% +/- 7.6% vs 11.1% +/- 4.2%; P < .001). Better survival was the result of both reduced incidence of relapse and transplantation-related mortality. The protective effect was seen in both female and male recipients, in both lymphoid and myeloid diseases; it was more evident in patients receiving transplants in remission than in chemotherapy-resistant relapse. Incidences of rejection and acute graft-versus-host disease were not significantly influenced. Multivariate analysis confirmed donor sex in parental donor transplantation as an independent prognostic factor for survival (hazard ratio, father vs mother = 2.36; P = .003). In contrast, in a control cohort of patients who received transplants from haploidentical siblings, donor sex had no influence on outcome. Although obtained in a retrospective analysis, these data suggest that the mother of the patient should be preferred as donor for haploidentical HSCT.Blood 05/2008; 112(7):2990-5. DOI:10.1182/blood-2008-01-135285 · 10.43 Impact Factor
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ABSTRACT: Prenatal repair of myelomeningocele, the most common form of spina bifida, may result in better neurologic function than repair deferred until after delivery. We compared outcomes of in utero repair with standard postnatal repair. We randomly assigned eligible women to undergo either prenatal surgery before 26 weeks of gestation or standard postnatal repair. One primary outcome was a composite of fetal or neonatal death or the need for placement of a cerebrospinal fluid shunt by the age of 12 months. Another primary outcome at 30 months was a composite of mental development and motor function. The trial was stopped for efficacy of prenatal surgery after the recruitment of 183 of a planned 200 patients. This report is based on results in 158 patients whose children were evaluated at 12 months. The first primary outcome occurred in 68% of the infants in the prenatal-surgery group and in 98% of those in the postnatal-surgery group (relative risk, 0.70; 97.7% confidence interval [CI], 0.58 to 0.84; P<0.001). Actual rates of shunt placement were 40% in the prenatal-surgery group and 82% in the postnatal-surgery group (relative risk, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001). Prenatal surgery also resulted in improvement in the composite score for mental development and motor function at 30 months (P=0.007) and in improvement in several secondary outcomes, including hindbrain herniation by 12 months and ambulation by 30 months. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at delivery. Prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00060606.).New England Journal of Medicine 02/2011; 364(11):993-1004. DOI:10.1056/NEJMoa1014379 · 54.42 Impact Factor