ChimerismPub Date : 2014-01-01DOI: 10.4161/chim.29562
Astrid G S van Halteren, Miranda P Dierselhuis, Tanja Netelenbos, Mirjam Fechter
{"title":"Donor parity no longer a barrier for female-to-male hematopoietic stem cell transplantation.","authors":"Astrid G S van Halteren, Miranda P Dierselhuis, Tanja Netelenbos, Mirjam Fechter","doi":"10.4161/chim.29562","DOIUrl":"https://doi.org/10.4161/chim.29562","url":null,"abstract":"<p><p>Allogeneic hematopoietic stem cell transplantation (HSCT) is a widely applied treatment for disorders mainly involving the hematopoietic system. The success of this treatment depends on many different patient- and donor-specific factors. Based on higher CD34+ yields and superior clinical outcomes associated with the use of male donors, males are generally seen as the preferred HSCT donor. In addition, female donors are notorious for bearing memory type lymphocytes induced by previous pregnancies; such alloimmune cells may provoke unwanted immune reactions such as graft-vs.-host disease in transplant recipients. Consequently, many transplant centers try to avoid parous donors, particularly when searching the best unrelated donor for a male patient. We recently showed that parous women with female offspring have an anti-male directed tolerogenic immune status comparable to that of nulliparous donors. As discussed in this article addendum, the sex of the donor's offspring combined with the presence of HY-specific T regulator cells are possibly better selection criteria than parity status per se. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"5 2","pages":"56-8"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.29562","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32429042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2014-01-01Epub Date: 2015-03-16DOI: 10.1080/19381956.2014.1002703
Marta Wegorzewska, Tom Le, Qizhi Tang, Tippi C MacKenzie
{"title":"Increased maternal T cell microchimerism in the allogeneic fetus during LPS-induced preterm labor in mice.","authors":"Marta Wegorzewska, Tom Le, Qizhi Tang, Tippi C MacKenzie","doi":"10.1080/19381956.2014.1002703","DOIUrl":"https://doi.org/10.1080/19381956.2014.1002703","url":null,"abstract":"<p><p>Fetal surgery is a promising strategy to treat fetuses with severe congenital abnormalities but its clinical applications are often limited by preterm labor. In normal pregnancy, multiple mechanisms protect the semi-allogeneic fetus from attack by maternal T cells. Maternal microchimerism (the presence of maternal cells in the fetus) has been suggested to be one mechanism of maternal-fetal tolerance in that it exposes the fetus to non-inherited maternal antigens and leads to the generation of fetal regulatory T cells that can suppress a maternal T cell response. Preterm labor may represent a breakdown of this robust tolerance network. We hypothesized that during inflammation-associated preterm labor, maternal leukocytes cross the maternal-fetal interface and enter the fetal circulation. Consistent with this hypothesis, we found that during preterm labor in mice, the percentage of maternal microchimerism in fetal blood increased and the frequency of fetuses with high levels of trafficking (greater than 0.5%) also increased. Finally, we showed that the maternal leukocytes trafficking into the fetus are primarily Gr-1(+) cells in both syngeneic and allogeneic pregnancy, while T cell trafficking into the fetus specifically increases during allogeneic pregnancies. Our results demonstrate that trafficking of maternal leukocytes during pregnancy is altered during preterm labor. Such alterations may be clinically significant in affecting maternal-fetal tolerance. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"5 3-4","pages":"68-74"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19381956.2014.1002703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33135985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2014-01-01DOI: 10.4161/chim.29844
Lucie Leveque, Kiarash Khosrotehrani
{"title":"Feto-maternal allo-immunity, regulatory T cells and predisposition to auto-immunity. Does it all start in utero?","authors":"Lucie Leveque, Kiarash Khosrotehrani","doi":"10.4161/chim.29844","DOIUrl":"https://doi.org/10.4161/chim.29844","url":null,"abstract":"<p><p>During gestation, maternal cells traffic to the fetus leading to the natural phenomenon of microchimerism. Although their persistence in offspring has been associated with several autoimmune disorders, the precise role of maternal cells in these disorders remains unclear. We aimed to evaluate whether alloreactive maternal T cells could directly trigger a graft-vs.-host like reaction or indirectly influence the development of the offspring's regulatory T cells (Treg) favoring autoimmunity. In a specific breeding strategy, we recently reported that maternal allogeneic T cells changed fetal Treg development and their quantities in mesenteric lymph nodes, leading to early signs of inflammation in the gut later in life. Although maternal microchimeric T cells were found in newborn tissues, we could not detect any cells in the gut from adult offspring where the inflammation occurred. Thus, strongly alloreactive maternal microchimeric T cells may indirectly drive the offspring to gut inflammation. We believe these results suggest a new mechanism for predisposition to auto-immunity. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"5 2","pages":"59-62"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.29844","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32575795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2014-01-01DOI: 10.4161/chim.28746
Uzma Mahmood, Keelin O'Donoghue
{"title":"Microchimeric fetal cells play a role in maternal wound healing after pregnancy.","authors":"Uzma Mahmood, Keelin O'Donoghue","doi":"10.4161/chim.28746","DOIUrl":"https://doi.org/10.4161/chim.28746","url":null,"abstract":"Fetal cells persist in mothers for decades after delivery: in a phenomenon called fetal microchimerism. While persistent fetal cells were first implicated in autoimmune disease, parallel studies in animal and human pregnancy now suggest that microchimeric fetal cells play a role in the response to tissue injury. The aim of this study was to investigate the impact of fetal microchimeric cells in the adult wound, using caesarean section (CS) as a model of wound healing in pregnancy. XY-FISH (fluorescence in situ hybridization) and immunostaining was used in multiple tissue sections from CS skin biopsies from 70 women, to locate, quantitate and characterize microchimeric male presumed-fetal cells. Y-FISH and Nested PCR was used to confirm XY-FISH results. XY-FISH demonstrated the presence of isolated 0–9 male fetal cells per section in the epidermis of the healed CS scars from only those women who had their first male child by CS. Both Y-FISH and Y-PCR confirmed the presence of fetal cells in CS scars. Combined FISH and immunostaining showed all male fetal cells present were keratinocytes, as they expressed cytokeratin, and were almost exclusively located in epidermis. Microchimeric fetal cells also expressed Collagen I, III, and TGF-β3 in healed maternal scars. Identification of male–presumed fetal cells in healed maternal CS scars after pregnancy suggests that, possibly in response to signals produced by maternal skin injury at CS, fetal cells migrate to the site of damage to become involved in maternal tissue repair, or proliferate locally.","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"5 2","pages":"40-52"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.28746","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32249845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2014-01-01Epub Date: 2015-03-16DOI: 10.1080/19381956.2015.1017241
Hilary S Gammill, Mary D Stephenson, Tessa M Aydelotte, J Lee Nelson
{"title":"Microchimerism in women with recurrent miscarriage.","authors":"Hilary S Gammill, Mary D Stephenson, Tessa M Aydelotte, J Lee Nelson","doi":"10.1080/19381956.2015.1017241","DOIUrl":"https://doi.org/10.1080/19381956.2015.1017241","url":null,"abstract":"<p><p>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. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"5 3-4","pages":"103-5"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19381956.2015.1017241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33017479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2014-01-01Epub Date: 2015-08-07DOI: 10.1080/19381956.2015.1052210
Rena Hirani, Zsolt J Balogh, Natalie J Lott, Jeremy M Hsu, David O Irving
{"title":"Leukodepleted blood components do not remove the potential for long-term transfusion-associated microchimerism in Australian major trauma patients.","authors":"Rena Hirani, Zsolt J Balogh, Natalie J Lott, Jeremy M Hsu, David O Irving","doi":"10.1080/19381956.2015.1052210","DOIUrl":"https://doi.org/10.1080/19381956.2015.1052210","url":null,"abstract":"<p><p>Despite the introduction of leukodepleted blood components, it has been shown that donor leukocyte engraftment (microchimerism) remains a long-term consequence of red blood cell (RBC) transfusion. The incidence of microchimerism may be affected by international disparities in blood processing methods or variations in transfusion practices. This study was conducted to determine the prevalence of microchimerism in Australian trauma patients. A secondary aim was to examine whether any patient complications correlated to the incidence of microchimerism. Australian trauma patients (n = 86) who had been transfused with red blood cell (RBC) units between 2000 and 2012 with an injury severity score (ISS) of greater than 15 were recruited. The prevalence of microchimerism was determined using genetic screening with a panel of insertion/deletion biallelic polymorphisms. The mean storage age of the transfused RBC units was 20 ± 8 days and the mean length of stay (LOS) in hospital was 40 ± 39 days. There were no significant associations in this study sample to bias for patient age, gender, number of transfused RBC units or ISS. Nine of the 55 (16.3%) patients transfused with non-leukodepleted blood components displayed an incidence of microchimerism. Of the 31 patients transfused with leukodepleted RBC units, 3 (9.6%) displayed an incidence of microchimerism. Therefore, despite the universal introduction of leukodepleted blood components in Australia, the prevalence of transfusion-associated microchimerism was found to be unchanged. Furthermore, half of the patients exhibiting microchimerism were recorded to have had splenic injury or required splenectomy at the time of transfusion. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"5 3-4","pages":"86-93"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19381956.2015.1052210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34074410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2014-01-01DOI: 10.4161/chim.28908
Michael Eikmans, Astrid G S van Halteren, Koen van Besien, Jon J van Rood, Jos J M Drabbels, Frans H J Claas
{"title":"Naturally acquired microchimerism: implications for transplantation outcome and novel methodologies for detection.","authors":"Michael Eikmans, Astrid G S van Halteren, Koen van Besien, Jon J van Rood, Jos J M Drabbels, Frans H J Claas","doi":"10.4161/chim.28908","DOIUrl":"https://doi.org/10.4161/chim.28908","url":null,"abstract":"<p><p>Microchimerism represents a condition where one individual harbors genetically distinct cell populations, and the chimeric population constitutes <1% of the total number of cells. The most common natural source of microchimerism is pregnancy. The reciprocal cell exchange between a mother and her child often leads to the stable engraftment of hematopoietic and non-hematopoietic stem cells in both parties. Interaction between cells from the mother and those from the child may result in maternal immune cells becoming sensitized to inherited paternal alloantigens of the child, which are not expressed by the mother herself. Vice versa, immune cells of the child may become sensitized toward the non-inherited maternal alloantigens of the mother. The extent of microchimerism, its anatomical location, and the sensitivity of the techniques used for detecting its presence collectively determine whether microchimerism can be detected in an individual. In this review, we focus on the clinical consequences of microchimerism in solid organ and hematopoietic stem cell transplantation, and propose concepts derived from data of epidemiologic studies. Next, we elaborate on the latest molecular methodology, including digital PCR, for determining in a reliable and sensitive way the extent of microchimerism. For the first time, tools have become available to isolate viable chimeric cells from a host background, so that the challenges of establishing the biologic mechanisms and function of these cells may finally be tackled. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"5 2","pages":"24-39"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.28908","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32287172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2014-01-01Epub Date: 2014-01-17DOI: 10.4161/chim.27778
Sonia Bakkour, Chris A R Baker, Alice F Tarantal, Li Wen, Michael P Busch, Tzong-Hae Lee, Joseph M McCune
{"title":"Analysis of maternal microchimerism in rhesus monkeys (Macaca mulatta) using real-time quantitative PCR amplification of MHC polymorphisms.","authors":"Sonia Bakkour, Chris A R Baker, Alice F Tarantal, Li Wen, Michael P Busch, Tzong-Hae Lee, Joseph M McCune","doi":"10.4161/chim.27778","DOIUrl":"https://doi.org/10.4161/chim.27778","url":null,"abstract":"<p><p>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. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"5 1","pages":"6-15"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.27778","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32051144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2014-01-01DOI: 10.4161/chim.29870
Jody Ye, Marta Vives-Pi, Kathleen M Gillespie
{"title":"Maternal microchimerism: friend or foe in type 1 diabetes?","authors":"Jody Ye, Marta Vives-Pi, Kathleen M Gillespie","doi":"10.4161/chim.29870","DOIUrl":"10.4161/chim.29870","url":null,"abstract":"<p><p>Increased levels of non-inherited maternal HLA alleles have been detected in the periphery of children with type 1 diabetes and an increased frequency of maternal cells have been identified in type 1 diabetes pancreas. It is now clear that the phenotype of these cells is pancreatic, supporting the hypothesis that maternal cells in human pancreas are derived from multipotent maternal progenitors. Here we hypothesize how increased levels of maternal cells could play a role in islet autoimmunity. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"5 2","pages":"21-3"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199804/pdf/chim-5-21.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32561929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2013-10-01Epub Date: 2013-09-30DOI: 10.4161/chim.26509
Senthil R Kumar, Sarah A Hansen, Sandra M Axiak-Bechtel, Jeffrey N Bryan
{"title":"The health effects of fetal microchimerism can be modeled in companion dogs.","authors":"Senthil R Kumar, Sarah A Hansen, Sandra M Axiak-Bechtel, Jeffrey N Bryan","doi":"10.4161/chim.26509","DOIUrl":"https://doi.org/10.4161/chim.26509","url":null,"abstract":"<p><p>Fetal microchimerism (FMC) has been described to have a range of effects on health and disease. Y-chromosomal DNA has been detected in Golden Retrievers suggesting persistent FMC. In that report, nine dogs had evidence of microchimerism without prior pregnancy. To further understand this finding, a dam with prior male live births giving birth to her fourth litter of puppies, all females, was evaluated for FMC along with two of her daughters. All three female dogs had evidence of Y-chromosomal DNA in their blood. This suggests that male cells carried by the dam from previous pregnancy trafficked to her daughters to establish microchimerism in younger siblings. Companion dogs share many of the same cancers as humans, have out-bred genetics, and share the human environment, making them optimal models of human disease. Understanding the impact of FMC on health and disease of dogs could elucidate mechanisms useful for clinical interventions in humans. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 4","pages":"139-41"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.26509","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31770454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}