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Lee J Nelson - One of the best experts on this subject based on the ideXlab platform.
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statistical methods for unusual count data examples from studies of Microchimerism
American Journal of Epidemiology, 2016Co-Authors: Katherine A Guthrie, Hilary S Gammill, Lee J Nelson, Vijayakrishna K Gadi, Mads Kamperjorgensen, Anne Tjonneland, Wendy LeisenringAbstract:: Natural acquisition of small amounts of foreign cells or DNA, referred to as Microchimerism, occurs primarily through maternal-fetal exchange during pregnancy. Microchimerism can persist long-term and has been associated with both beneficial and adverse human health outcomes. Quantitative Microchimerism data present challenges for statistical analysis, including a skewed distribution, excess zero values, and occasional large values. Methods for comparing Microchimerism levels across groups while controlling for covariates are not well established. We compared statistical models for quantitative Microchimerism values, applied to simulated data sets and 2 observed data sets, to make recommendations for analytic practice. Modeling the level of quantitative Microchimerism as a rate via Poisson or negative binomial model with the rate of detection defined as a count of Microchimerism genome equivalents per total cell equivalents tested utilizes all available data and facilitates a comparison of rates between groups. We found that both the marginalized zero-inflated Poisson model and the negative binomial model can provide unbiased and consistent estimates of the overall association of exposure or study group with Microchimerism detection rates. The negative binomial model remains the more accessible of these 2 approaches; thus, we conclude that the negative binomial model may be most appropriate for analyzing quantitative Microchimerism data.
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cellular fetal Microchimerism in preeclampsia
Hypertension, 2013Co-Authors: Hilary S Gammill, Katherine A Guthrie, Tessa M. Aydelotte, Evangelyn Nkwopara, Lee J NelsonAbstract:Previous studies have shown elevated concentrations of free fetal DNA and erythroblasts in maternal circulation in women with preeclampsia compared with those with normal pregnancy. Pluripotent and immunocompetent fetal cells also transfer to the maternal circulation during pregnancy, but whether concentrations of fetal mononuclear cells also differed in preeclampsia was unknown. We sought to quantify cellular fetal Microchimerism in maternal circulation in women with preeclampsia and healthy controls. We studied women with preeclampsia and compared them with women with healthy pregnancies at similar gestational age. To identify a targetable polymorphism unique to the fetus to quantify fetal Microchimerism, participants and family members were genotyped for the human leukocyte antigen loci DRB1, DQA1, and DQB1, as well as several other polymorphisms. A panel of polymorphism-specific quantitative polymerase chain reaction assays was used to identify and quantify fetal Microchimerism in maternal peripheral blood mononuclear cells. Of 53 preeclampsia samples tested for cellular fetal Microchimerism, 17 (32%) were positive when compared with 6 of 57 (6%) control samples (unadjusted odds ratio for detection, 4.0; 95% confidence interval, 1.5–11.1; P =0.007). The concentration of cellular fetal Microchimerism (expressed as genome equivalents of fetal Microchimerism per 100 000 maternal genome equivalents) was also higher among women with preeclampsia: median 0.0, mean 5.7, range 0 to 153.7, compared with those with controls: median 0.0, mean 0.3, range 0 to 9.1, P =0.002. We conclude that women with preeclampsia harbor cellular fetal Microchimerism more commonly and at higher concentrations compared with women with uncomplicated pregnancy. The functional capacity and phenotype of these fetal cells are not yet known.
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male Microchimerism in the human female brain
PLOS ONE, 2012Co-Authors: William F N Chan, Lee J Nelson, Katherine A Guthrie, Cecile Gurnot, Thomas J Montine, Joshua A SonnenAbstract:In humans, naturally acquired Microchimerism has been observed in many tissues and organs. Fetal Microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for Microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus). Targeting the Y-chromosome-specific DYS14 gene, we performed real-time quantitative PCR in autopsied brain from women without clinical or pathologic evidence of neurologic disease (n=26), or women who had Alzheimer's disease (n=33). We report that 63% of the females (37 of 59) tested harbored male Microchimerism in the brain. Male Microchimerism was present in multiple brain regions. Results also suggested lower prevalence (p=0.03) and concentration (p=0.06) of male Microchimerism in the brains of women with Alzheimer's disease than the brains of women without neurologic disease. In conclusion, male Microchimerism is frequent and widely distributed in the human female brain.
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Microchimerism in the rheumatoid nodules of patients with rheumatoid arthritis
Arthritis & Rheumatism, 2012Co-Authors: William F N Chan, Christopher J Atkins, David Naysmith, Nicholas Van Der Westhuizen, Lee J NelsonAbstract:Objective The rheumatoid nodule is a lesion commonly found on extraarticular areas prone to mechanic trauma. When present with inflammatory symmetric polyarthritis, it is pathognomonic of rheumatoid arthritis (RA), an autoimmune disease in which naturally acquired Microchimerism has previously been described and can sometimes contribute to RA risk. Since RA patients harbor Microchimerism in the blood, we hypothesized that Microchimerism is also present in rheumatoid nodules and could play a role in rheumatoid nodule formation. This study was undertaken to investigate rheumatoid nodules for Microchimerism. Methods Rheumatoid nodules were tested for Microchimerism by real-time quantitative polymerase chain reaction (qPCR). The rheumatoid nodules of 29 female patients were tested for a Y chromosome–specific sequence. After HLA genotyping of patients and family members, rheumatoid nodules from 1 man and 14 women were tested by HLA-specific qPCR, targeting a nonshared HLA allele of the potential Microchimerism source. Results were expressed as genome equivalents of microchimeric cells per 105 patient genome equivalents (GE/105). Results Rheumatoid nodules from 21% of the female patients contained male DNA (range <0.5, 10.3 GE/105). By HLA-specific qPCR, 60% of patients were microchimeric (range 0, 18.5 GE/105). Combined Microchimerism prevalence was 47%. A fetal or maternal source was identified in all patients who tested positive by HLA-specific qPCR. Unexpectedly, a few rheumatoid nodules also contained Microchimerism without evidence of a fetal or maternal source, suggesting alternative sources. Conclusion Our findings indicate that Microchimerism is frequently present in the rheumatoid nodules of RA patients. Since Microchimerism is genetically disparate, whether Microchimerism in rheumatoid nodules serves as an allogeneic stimulus or allogeneic target warrants further investigation.
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pregnancy Microchimerism and the maternal grandmother
PLOS ONE, 2011Co-Authors: Hilary S Gammill, Lee J Nelson, Wendy Leisenring, Tessa M. Aydelotte, Nathalie C Lambert, Kristina Adams M Waldorf, Joelle LucasAbstract:Background A woman of reproductive age often harbors a small number of foreign cells, referred to as Microchimerism: a preexisting population of cells acquired during fetal life from her own mother, and newly acquired populations from her pregnancies. An intriguing question is whether the population of cells from her own mother can influence either maternal health during pregnancy and/or the next generation (grandchildren). Methodology/Principal Findings Microchimerism from a woman's (i.e. proband's) own mother (mother-of-the-proband, MP) was studied in peripheral blood samples from women followed longitudinally during pregnancy who were confirmed to have uncomplicated obstetric outcomes. Women with preeclampsia were studied at the time of diagnosis and comparison made to women with healthy pregnancies matched for parity and gestational age. Participants and family members were HLA-genotyped for DRB1, DQA1, and DQB1 loci. An HLA polymorphism unique to the woman's mother was identified, and a panel of HLA-specific quantitative PCR assays was employed to identify and quantify Microchimerism. Microchimerism from the MP was identified during normal, uncomplicated pregnancy, with a peak concentration in the third trimester. The likelihood of detection increased with advancing gestational age. For each advancing trimester, there was a 12.7-fold increase in the probability of detecting Microchimerism relative to the prior trimester, 95% confidence intervals 3.2, 50.3, p<0.001. None of the women with preeclampsia, compared with 30% of matched healthy women, had Microchimerism (p = 0.03). Conclusions/Significance These results show that Microchimerism from a woman's own mother is detectable in normal pregnancy and diminished in preeclampsia, supporting the previously unexplored hypothesis that MP Microchimerism may be a marker reflecting healthy maternal adaptation to pregnancy.
Hilary S Gammill - One of the best experts on this subject based on the ideXlab platform.
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Microchimerism defining and redefining the prepregnancy context a review
Placenta, 2017Co-Authors: Hilary S Gammill, W E HarringtonAbstract:Bidirectional transplacental exchange characterizes human pregnancy. Cells exchanged between mother and fetus can durably persist as Microchimerism and may have both short- and long-term consequences for the recipient. The amount, type, and persistence of Microchimerism are influenced by obstetric characteristics, pregnancy complications, exposures to infection, and other factors. A reproductive-aged woman enters pregnancy harboring previously acquired microchimeric “grafts,” which may influence her preconception health and her subsequent pregnancy outcomes. Many questions remain to be answered about Microchimerism with broad-ranging implications. This review will summarize key aspects of this field of research and propose important questions to be addressed moving forward.
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statistical methods for unusual count data examples from studies of Microchimerism
American Journal of Epidemiology, 2016Co-Authors: Katherine A Guthrie, Hilary S Gammill, Lee J Nelson, Vijayakrishna K Gadi, Mads Kamperjorgensen, Anne Tjonneland, Wendy LeisenringAbstract:: Natural acquisition of small amounts of foreign cells or DNA, referred to as Microchimerism, occurs primarily through maternal-fetal exchange during pregnancy. Microchimerism can persist long-term and has been associated with both beneficial and adverse human health outcomes. Quantitative Microchimerism data present challenges for statistical analysis, including a skewed distribution, excess zero values, and occasional large values. Methods for comparing Microchimerism levels across groups while controlling for covariates are not well established. We compared statistical models for quantitative Microchimerism values, applied to simulated data sets and 2 observed data sets, to make recommendations for analytic practice. Modeling the level of quantitative Microchimerism as a rate via Poisson or negative binomial model with the rate of detection defined as a count of Microchimerism genome equivalents per total cell equivalents tested utilizes all available data and facilitates a comparison of rates between groups. We found that both the marginalized zero-inflated Poisson model and the negative binomial model can provide unbiased and consistent estimates of the overall association of exposure or study group with Microchimerism detection rates. The negative binomial model remains the more accessible of these 2 approaches; thus, we conclude that the negative binomial model may be most appropriate for analyzing quantitative Microchimerism data.
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Microchimerism in women with recurrent miscarriage.
Chimerism, 2014Co-Authors: Hilary S Gammill, Mary D. Stephenson, Tessa M. Aydelotte, J. Lee NelsonAbstract:Miscarriage is the most common pregnancy complication, and recurrent miscarriage (3 or more consecutive pregnancy losses) affects 1–5% of couples. Maternal-fetal exchange and the persistence of exchanged material as Microchimerism appears to be disrupted in complicated pregnancies. We recently conducted a longitudinal cohort study of Microchimerism in women with recurrent miscarriage. Our initial data raise multiple questions that require further investigation. Here, we review our data from this recent study and provide additional information regarding Microchimerism in the granulocyte cell layer. This area of investigation offers a unique window into early reproductive events, and future related studies have the potential to identify novel therapeutic approaches and insights into human evolution.
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Microchimerism in recurrent miscarriage
Cellular & Molecular Immunology, 2014Co-Authors: Hilary S Gammill, Mary D. Stephenson, Tessa M. Aydelotte, J. Lee NelsonAbstract:Maternal–fetal cell exchange during pregnancy results in acquisition of Microchimerism, which can durably persist in both recipients. Naturally acquired Microchimerism may impact maternal–fetal interaction in pregnancy. We conducted studies to ask whether Microchimerism that a woman acquired from her own mother is detectable before or during pregnancy in women with recurrent miscarriage. Fetal Microchimerism was also assayed. Women with primary idiopathic recurrent miscarriage (n=23) and controls (n=31) were studied. Genotyping was conducted for probands, their mothers and the fetus, a non-shared polymorphism identified and quantitative polymerase chain reaction performed to measure Microchimerismin peripheral blood mononuclear cells. Preconception comparisons were made between recurrent miscarriage subjects and controls, using logistic regression and Wilcoxon rank sum. Longitudinal Microchimerism in subsequent pregnancies of recurrent miscarriage subjects was described. There was a trend toward lower preconception detection of Microchimerism in recurrent miscarriage versus controls, 6% vs. 19% (1/16 vs. 6/31, P=0.2). During pregnancy, 3/11 (27%) of recurrent miscarriage subjects who went on to have a birth had detection of Microchimerism from their own mother, whereas neither of two subjects who went on to miscarry had detection (0/2). This initial data suggest that Microchimerism from a woman's own mother, while detectable in women with recurrent miscarriage, may differ from controls and according to subsequent pregnancy outcome. Further studies are needed to determine the cell types, quantities and any potential functional role of Microchimerism in recurrent miscarriage.
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cellular fetal Microchimerism in preeclampsia
Hypertension, 2013Co-Authors: Hilary S Gammill, Katherine A Guthrie, Tessa M. Aydelotte, Evangelyn Nkwopara, Lee J NelsonAbstract:Previous studies have shown elevated concentrations of free fetal DNA and erythroblasts in maternal circulation in women with preeclampsia compared with those with normal pregnancy. Pluripotent and immunocompetent fetal cells also transfer to the maternal circulation during pregnancy, but whether concentrations of fetal mononuclear cells also differed in preeclampsia was unknown. We sought to quantify cellular fetal Microchimerism in maternal circulation in women with preeclampsia and healthy controls. We studied women with preeclampsia and compared them with women with healthy pregnancies at similar gestational age. To identify a targetable polymorphism unique to the fetus to quantify fetal Microchimerism, participants and family members were genotyped for the human leukocyte antigen loci DRB1, DQA1, and DQB1, as well as several other polymorphisms. A panel of polymorphism-specific quantitative polymerase chain reaction assays was used to identify and quantify fetal Microchimerism in maternal peripheral blood mononuclear cells. Of 53 preeclampsia samples tested for cellular fetal Microchimerism, 17 (32%) were positive when compared with 6 of 57 (6%) control samples (unadjusted odds ratio for detection, 4.0; 95% confidence interval, 1.5–11.1; P =0.007). The concentration of cellular fetal Microchimerism (expressed as genome equivalents of fetal Microchimerism per 100 000 maternal genome equivalents) was also higher among women with preeclampsia: median 0.0, mean 5.7, range 0 to 153.7, compared with those with controls: median 0.0, mean 0.3, range 0 to 9.1, P =0.002. We conclude that women with preeclampsia harbor cellular fetal Microchimerism more commonly and at higher concentrations compared with women with uncomplicated pregnancy. The functional capacity and phenotype of these fetal cells are not yet known.
Michael P Busch - One of the best experts on this subject based on the ideXlab platform.
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analysis of maternal Microchimerism in rhesus monkeys macaca mulatta using real time quantitative pcr amplification of mhc polymorphisms
Chimerism, 2014Co-Authors: Sonia Bakkour, Michael P Busch, Chris A R Baker, Alice F Tarantal, Joseph M MccuneAbstract:Although pregnancy-associated Microchimerism is known to exist in humans, its clinical significance remains unclear. Fetal Microchimerism has been documented in rhesus monkeys, but the trafficking and persistence of maternal cells in the monkey fetus and infant have not been fully explored. To investigate the frequency of maternal Microchimerism in the rhesus monkey (Macaca mulatta), a real-time polymerase chain reaction (PCR) strategy was developed and validated to target polymorphic major histocompatibility complex (MHC) gene sequences. Informative PCR assays were identified for 19 of 25 dams and their respective offspring. Analyses were performed on tissues (thymus, liver, spleen, lymph nodes, and bone marrow) and peripheral blood mononuclear cells (PBMCs) collected prenatally and postnatally in a subset of animals. Seven of 19 monkeys had detectable maternal Microchimerism in at least one compartment (range: 0.001–1.9% chimeric cells). In tissues, maternal Microchimerism was found in 2 of 7 fetuses and 3 of 12 juveniles (1–1.5 years of age), and most of the animals that were positive had microchimeric cells in more than one tissue. Maternal Microchimerism was detected in PBMCs from all (4 of 4) fetuses. These observations suggest that maternal Microchimerism occurs in the rhesus monkey fetus and can be detected in tissues in a subset of offspring after birth.
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transfusion associated Microchimerism the hybrid within
Transfusion Medicine Reviews, 2013Co-Authors: Evan M Bloch, Rachael P Jackman, Michael P BuschAbstract:Abstract Microchimerism, the coexistence of genetically disparate populations of cells in a receptive host, is well described in both clinical and physiological settings, including transplantation and pregnancy. Microchimerism can also occur after allogeneic blood transfusion in traumatically injured patients, where donor cells have been observed decades after transfusion. To date, transfusion-associated Microchimerism (TA-MC) appears confined to this clinical subset, most likely due to the immune perturbations that occur after severe trauma that allow foreign donor cells to survive. Transfusion-associated Microchimerism appears to be unaffected by leukoreduction and has been documented after transfusion with an array of blood products. The only significant predictor of TA-MC to date is the age of red cells, with fresher units associated with higher risk. Thus far, no adverse clinical effect has been observed in limited studies of TA-MC. There are, however, hypothesized links to transfusion-associated graft vs host disease that may be unrecognized and consequently underreported. Microchimerism in other settings has gained increasing attention owing to a plausible link to autoimmune diseases, as well as its diagnostic and therapeutic potential vis-a-vis antenatal testing and adoptive immunotherapy, respectively. Furthermore, Microchimerism provides a tool to further our understanding of immune tolerance and regulation.
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the tnf 308a polymorphism is associated with Microchimerism in transfused trauma patients
Blood, 2008Co-Authors: Ryan M Gill, Garth H Utter, William Reed, Dan Chafets, Michael P BuschAbstract:Microchimerism (MC), defined as the persistence of allogeneic cells at low concentrations, is well documented in transfused trauma patients. We hypothesized that genetic polymorphisms linked to cytokine production could contribute to trauma-induced immune modulation and development of Microchimerism after transfusion of trauma patients. We used high-throughput SYBR-green-based genotyping of single nucleotide polymorphisms (SNPs) to characterize 59 transfused trauma patients, with MC (n = 30) and without MC (n = 29), for 4 functionally significant SNPs: TNF (−308), IL 10 (−1082), IFNG (+874), and TGFB1 (+915). We then compared likelihood for development of MC and the magnitude of immune suppression among subjects with and without these selected immune response SNPs. We identified a significant association between TNF (−308A) SNP and both development of MC and diminished immune responsiveness. Hence predisposing genetic factors may explain, in part, why only a subset of trauma patients develops transfusion-associated Microchimerism.
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Microchimerism in transfused trauma patients is associated with diminished donor specific lymphocyte response
Journal of Trauma-injury Infection and Critical Care, 2005Co-Authors: Garth H Utter, John T Owings, Teresa Paglieroni, William Reed, Robert C Gosselin, Paul V Holland, Michael P BuschAbstract:Background: Blood transfusion can result in long-term survival of donor leukocyte subpopulations, or Microchimerism, in the peripheral blood of injured patients. Neither injury severity nor the number of transfusions is associated with its occurrence. We sought to determine whether changes in general or antigen-specific lymphocyte activation may be associated with the subsequent development of Microchimerism. Methods: We evaluated 63 transfused trauma patients, which we compared with 10 non-transfused trauma patients and 10 healthy control subjects. Of the 63 transfused patients, 31 were known to have evidence of Microchimerism at hospital discharge with real-time quantitative PCR for non-recipient HLA DR alleles. We assessed lymphocyte response to phytohemagglutinin (PHA) using blood sampled upon arrival to the hospital (before transfusion) and at discharge. We performed one-way mixed leukocyte cultures (MLC) with pre-transfusion recipient specimens to assess recipient lymphocyte response to mitomycin-C treated donor cells and vice versa. Results: Lymphocyte response to PHA in microchimeric transfusion recipients was lower at admission (before transfusion) and discharge than in non-microchimeric recipients. Lymphocytes from microchimeric patients had less response to donor cells than did lymphocytes from non-microchimeric patients. Microchimeric patients also more frequently had diminished lymphocyte response to a single blood donor on MLC. Conclusions: Transfusion-associated Microchimerism is correlated with diminished response to mitogen challenge as well as to specific alloantigenic challenges. This Microchimerism is predated by diminished lymphocyte response to a specific blood donor in many instances. The blood donor associated with this diminished alloantigenic lymphocyte response may be the source of microchimeric cells present in the recipient.
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blood transfusion is associated with donor leukocyte Microchimerism in trauma patients
Journal of Trauma-injury Infection and Critical Care, 2004Co-Authors: Garth H Utter, John T Owings, Teresa Paglieroni, William Reed, Robert C Gosselin, Paul V Holland, Michael P BuschAbstract:Introduction: Blood transfusion can result in survival of donor leukocyte subpopulations in the recipient. Persistence of donor leukocytes in the transfusion recipient is termed Microchimerism. Microchimerism likely reflects engraftment of the recipient with donor hematopoietic stem cells and is very uncommon with transfusion for elective surgery, sickle cell anemia, thalassemia, and HIV. We have found, however, that Microchimerism may be more common in trauma patients. Objective: To determine how frequently transfusion after trauma is associated with Microchimerism. Methods: We prospectively enrolled 45 trauma patients who were transfused ≥2 units of PRBCs. We sampled blood before hospital discharge and determined Microchimerism by polymerase chain reaction (PCR) analysis of specimens using quantitative allele-specific HLA DR assays to detect non-recipient alleles. Data are expressed as median with interquartile range. Results: Patients had a median age of 38 (interquartile range 25, 58) years, ISS of 19 (13, 29), and mortality of 7%. Seventy-eight percent were men, and 84% had blunt trauma. Patients received a median of 6 (4, 16) (range 2, 87) units of PRBCs. Of the 45 patients, 24 (53%) had evidence of Microchimerism. Compared with patients without evidence of Microchimerism, these patients had no difference in mean age, gender, ISS, units of PRBCs transfused, time from transfusion to blood sampling, or proportion that underwent splenectomy. Twenty-one of the 24 patients with Microchimerism had only 1 or 2 non-recipient DR alleles identified by PCR. Conclusions: Transfusion after trauma is associated with over half of recipients having evidence of Microchimerism. Age, sex, ISS, and splenectomy of the recipient and the number of transfused units did not correlate with Microchimerism. Because the median time from trans' fusion to sampling for PCR analysis was not longer in the group without Microchimerism, it is unlikely Microchimerism is due merely to failure of the recipient to clear transfused donor leukocytes.
Hiroh Saji - One of the best experts on this subject based on the ideXlab platform.
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fetal maternal Microchimerism impact on hematopoietic stem cell transplantation
Current Opinion in Immunology, 2005Co-Authors: Tatsuo Ichinohe, Takanori Teshima, Kenichi Matsuoka, Etsuko Maruya, Hiroh SajiAbstract:Reciprocal cell traffic between mother and fetus during pregnancy gives rise to postpartum fetal-maternal lymphohematopoietic Microchimerism, which is frequently detected in blood or tissue from healthy individuals. Although such Microchimerism has been implicated in the pathogenesis of autoimmune diseases and tissue repair, recent clinical experiences have suggested the association of Microchimerism with acquired immunologic hyporesponsiveness to non-inherited maternal HLA antigens (NIMAs) or inherited paternal HLA antigens (IPAs); T cell-replete HLA-haploidentical hematopoietic stem cell transplantation from a microchimeric IPA/NIMA-mismatched donor confers relatively lower incidence of severe graft-versus-host disease. The underlying mechanisms by which fetal-maternal Microchimerism contributes to IPA/NIMA-specific tolerance are still elusive, although emerging experimental evidence suggests an involvement of the central deletion of IPA/NIMA-reactive T cells, the induction of peripheral regulatory T cells, and affinity-dependent modulation of NIMA-reactive B cells.
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Long-term Feto-Maternal Microchimerism: Nature’s Hidden Clue for Alternative Donor Hematopoietic Cell Transplantation?
International Journal of Hematology, 2002Co-Authors: Tatsuo Ichinohe, Etsuko Maruya, Hiroh SajiAbstract:During pregnancy, fetal hematopoietic cells carrying paternal human leukocyte antigens (HLA) migrate into maternal circulation, and, vice versa, maternal nucleated cells can be detected in fetal organs and umbilical cord blood, indicating the presence of bidirectional cell traffic between mother and fetus. By taking advantage of fluorescence in-situ hybridization or polymerase chain reaction-based techniques, researchers recently found that postpartum persistence of such reciprocal chimerism was common among healthy individuals and may sometimes cause tissue chimerism.Although the biological significance of long-lasting feto-maternal Microchimerism is unknown, a number of investigations have suggested its association with the development of “autoimmune” diseases such as systemic sclerosis. However, the very common presence of feto-maternal Microchimerism among subjects without any autoimmune attack may allow us the more appealing hypothesis that it is an indicator for the acquired immunological hyporesponsiveness to noninherited maternal or fetal HLA antigens. An offspring’s tolerance to noninherited maternal antigens has been clinically suggested by the retrospective analysis of renal transplantations or haploidentical hematopoietic stem cell transplantations, and whether postpartum mothers can tolerate paternally derived fetal antigens is an intriguing question. Although an exact linkage between Microchimerism and transplantation tolerance is yet to be elucidated, long-term acceptance of a recipient’s cell in the donor may have a favorable effect on preventing the development of severe graft-versus-host disease, and the donor cell Microchimerism in the recipient might facilitate the graft acceptance. If this concept holds true, HLA-mismatched hematopoietic stem cell transplantation would be more feasible among haploidentical family members mutually linked with feto-maternal Microchimerism. Further studies are warranted to investigate the potential role of feto-maternal Microchimerism in human transplantation medicine.
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long term feto maternal Microchimerism nature s hidden clue for alternative donor hematopoietic cell transplantation
International Journal of Hematology, 2002Co-Authors: Tatsuo Ichinohe, Etsuko Maruya, Hiroh SajiAbstract:During pregnancy, fetal hematopoietic cells carrying paternal human leukocyte antigens (HLA) migrate into maternal circulation, and, vice versa, maternal nucleated cells can be detected in fetal organs and umbilical cord blood, indicating the presence of bidirectional cell traffic between mother and fetus. By taking advantage of fluorescence in-situ hybridization or polymerase chain reaction-based techniques, researchers recently found that postpartum persistence of such reciprocal chimerism was common among healthy individuals and may sometimes cause tissue chimerism.Although the biological significance of long-lasting feto-maternal Microchimerism is unknown, a number of investigations have suggested its association with the development of “autoimmune” diseases such as systemic sclerosis. However, the very common presence of feto-maternal Microchimerism among subjects without any autoimmune attack may allow us the more appealing hypothesis that it is an indicator for the acquired immunological hyporesponsiveness to noninherited maternal or fetal HLA antigens. An offspring’s tolerance to noninherited maternal antigens has been clinically suggested by the retrospective analysis of renal transplantations or haploidentical hematopoietic stem cell transplantations, and whether postpartum mothers can tolerate paternally derived fetal antigens is an intriguing question. Although an exact linkage between Microchimerism and transplantation tolerance is yet to be elucidated, long-term acceptance of a recipient’s cell in the donor may have a favorable effect on preventing the development of severe graft-versus-host disease, and the donor cell Microchimerism in the recipient might facilitate the graft acceptance. If this concept holds true, HLA-mismatched hematopoietic stem cell transplantation would be more feasible among haploidentical family members mutually linked with feto-maternal Microchimerism. Further studies are warranted to investigate the potential role of feto-maternal Microchimerism in human transplantation medicine.
Nathalie C Lambert - One of the best experts on this subject based on the ideXlab platform.
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pregnancy Microchimerism and the maternal grandmother
PLOS ONE, 2011Co-Authors: Hilary S Gammill, Lee J Nelson, Wendy Leisenring, Tessa M. Aydelotte, Nathalie C Lambert, Kristina Adams M Waldorf, Joelle LucasAbstract:Background A woman of reproductive age often harbors a small number of foreign cells, referred to as Microchimerism: a preexisting population of cells acquired during fetal life from her own mother, and newly acquired populations from her pregnancies. An intriguing question is whether the population of cells from her own mother can influence either maternal health during pregnancy and/or the next generation (grandchildren). Methodology/Principal Findings Microchimerism from a woman's (i.e. proband's) own mother (mother-of-the-proband, MP) was studied in peripheral blood samples from women followed longitudinally during pregnancy who were confirmed to have uncomplicated obstetric outcomes. Women with preeclampsia were studied at the time of diagnosis and comparison made to women with healthy pregnancies matched for parity and gestational age. Participants and family members were HLA-genotyped for DRB1, DQA1, and DQB1 loci. An HLA polymorphism unique to the woman's mother was identified, and a panel of HLA-specific quantitative PCR assays was employed to identify and quantify Microchimerism. Microchimerism from the MP was identified during normal, uncomplicated pregnancy, with a peak concentration in the third trimester. The likelihood of detection increased with advancing gestational age. For each advancing trimester, there was a 12.7-fold increase in the probability of detecting Microchimerism relative to the prior trimester, 95% confidence intervals 3.2, 50.3, p<0.001. None of the women with preeclampsia, compared with 30% of matched healthy women, had Microchimerism (p = 0.03). Conclusions/Significance These results show that Microchimerism from a woman's own mother is detectable in normal pregnancy and diminished in preeclampsia, supporting the previously unexplored hypothesis that MP Microchimerism may be a marker reflecting healthy maternal adaptation to pregnancy.
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Pregnancy, Microchimerism, and the maternal grandmother.
PLOS ONE, 2011Co-Authors: Hilary S Gammill, Wendy Leisenring, Tessa M. Aydelotte, Nathalie C Lambert, Kristina Adams M Waldorf, Joelle Lucas, J. Lee NelsonAbstract:Background A woman of reproductive age often harbors a small number of foreign cells, referred to as Microchimerism: a preexisting population of cells acquired during fetal life from her own mother, and newly acquired populations from her pregnancies. An intriguing question is whether the population of cells from her own mother can influence either maternal health during pregnancy and/or the next generation (grandchildren). Methodology/Principal Findings Microchimerism from a woman's (i.e. proband's) own mother (mother-of-the-proband, MP) was studied in peripheral blood samples from women followed longitudinally during pregnancy who were confirmed to have uncomplicated obstetric outcomes. Women with preeclampsia were studied at the time of diagnosis and comparison made to women with healthy pregnancies matched for parity and gestational age. Participants and family members were HLA-genotyped for DRB1, DQA1, and DQB1 loci. An HLA polymorphism unique to the woman's mother was identified, and a panel of HLA-specific quantitative PCR assays was employed to identify and quantify Microchimerism. Microchimerism from the MP was identified during normal, uncomplicated pregnancy, with a peak concentration in the third trimester. The likelihood of detection increased with advancing gestational age. For each advancing trimester, there was a 12.7-fold increase in the probability of detecting Microchimerism relative to the prior trimester, 95% confidence intervals 3.2, 50.3, p
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male Microchimerism in women without sons quantitative assessment and correlation with pregnancy history
The American Journal of Medicine, 2005Co-Authors: Katherine A Guthrie, Nathalie C Lambert, Allison J Porter, Laurence S Loubiere, Margaret M Madeleine, Anne M Stevens, Heidi M HermesAbstract:Abstract Purpose Fetal Microchimerism, derived from fetal cells that persist after pregnancy, is usually evaluated by tests for male Microchimerism in women who gave birth to sons. We investigated male Microchimerism in women without sons and examined correlation with prior pregnancy history. Immunologic consequences of Microchimerism are unknown. We studied healthy women and women with rheumatoid arthritis (RA). Methods Y-chromosome-specific real-time quantitative polymerase chain reaction was used to test peripheral blood mononuclear cells of 120 women (49 healthy and 71 with RA). Results were expressed as the number of male cells that would be equivalent to the total amount of male DNA detected within a sample containing the equivalent of 100000 female cells. Results Male Microchimerism was found in 21% of women overall. Healthy women and women with RA did not significantly differ (24% vs 18%). Results ranged from the DNA equivalent of 0 to 20.7 male cells per 100000 female cells. Women were categorized into 4 groups according to pregnancy history. Group A had only daughters (n = 26), Group B had spontaneous abortions (n = 23), Group C had induced abortions (n = 23), and Group D were nulligravid (n = 48). Male Microchimerism prevalence was significantly greater in Group C than other groups (8%, 22%, 57%, 10%, respectively). Levels were also significantly higher in the induced abortion group. Conclusions Male Microchimerism was not infrequent in women without sons. Besides known pregnancies, other possible sources of male Microchimerism include unrecognized spontaneous abortion, vanished male twin, an older brother transferred by the maternal circulation, or sexual intercourse. Male Microchimerism was significantly more frequent and levels were higher in women with induced abortion than in women with other pregnancy histories. Further studies are needed to determine specific origins of male Microchimerism in women.
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male Microchimerism in women with systemic sclerosis and healthy women who have never given birth to a son
Annals of the Rheumatic Diseases, 2005Co-Authors: Nathalie C Lambert, Anne M Stevens, Daniel E Furst, Jennifer M Pang, Timothy D Erickson, J L NelsonAbstract:Background: Male DNA or cells are often used to measure Microchimerism in a woman. In studies of autoimmune diseases male Microchimerism is most often attributed to the previous birth of a son. Objective: To determine the frequency of male Microchimerism in healthy women or women with systemic sclerosis who had never given birth to a son. Methods: Real time quantitative polymerase chain reaction targeting the Y chromosome specific sequence DYS14 was employed to test DNA extracted from peripheral blood mononuclear cells of 26 women with systemic sclerosis and 23 healthy women who had never given birth to a son. Results are expressed as the genome equivalent number of male cells per million host cells (gEq/mil). Results: Male DNA was found in 15% of women with systemic sclerosis (range 0 to 23.7 gEq/mil) and in 13% of healthy women (range 0 to 5.1 gEq/mil). Although two women with male DNA had an induced abortion, most had no history of spontaneous or induced abortion (either systemic sclerosis or healthy). Conclusions: Microchimerism with male DNA can be found in the circulation of women who have never given birth to a son. Thus sources other than a male birth must be considered when male DNA is used to measure Microchimerism. Although other studies are needed, there was no apparent difference in women with systemic sclerosis and healthy women. Possible sources of male DNA include unrecognised male pregnancy or unrecognised male twin, an older male sibling with transfer through the maternal circulation, or sexual intercourse alone.
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Microchimerism in autoimmune disease more questions than answers
Autoimmunity Reviews, 2003Co-Authors: Nathalie C Lambert, Lee J NelsonAbstract:Recent studies indicate cell traffic occurs between the fetus and mother during pregnancy and that low numbers of fetal cells commonly persist in the maternal circulation for years thereafter. Microchimerism refers to a small number of cells or DNA from one individual harbored in another individual. Autoimmune diseases are more common among women and often increase in incidence following reproductive years. Chronic graft vs. host disease is an iatrogenic form of chimerism with similarities to some autoimmune diseases for which the HLA relationship of donor and host are of central importance. When considered together, these observations led to the hypothesis that Microchimerism and HLA relationships of host and non-host cells are involved in autoimmune disease. The hypothesis is applicable to men, children and women without pregnancies because there are other sources of Microchimerism, including from a twin, the mother or a blood transfusion. Microchimerism has now been investigated in a number of different diseases with some results supporting a potential role in disease pathogenesis. However, fetal and maternal Microchimerism are also found in organs affected by non-autoimmune conditions. Moreover, Microchimerism is commonly detected in the peripheral blood of healthy individuals raising the intriguing question of whether these cells are simple remnants of pregnancy or whether they might also have beneficial effects for the host.