ChimerismPub Date : 2013-10-01Epub Date: 2013-05-03DOI: 10.4161/chim.24915
Suzanne E Peterson, J Lee Nelson, Vijayakrishna K Gadi, Hilary S Gammill
{"title":"Fetal cellular microchimerism in miscarriage and pregnancy termination.","authors":"Suzanne E Peterson, J Lee Nelson, Vijayakrishna K Gadi, Hilary S Gammill","doi":"10.4161/chim.24915","DOIUrl":"https://doi.org/10.4161/chim.24915","url":null,"abstract":"<p><p>Fetal cells transfer to the mother during pregnancy and can persist long-term as microchimerism. Acquisition of microchimerism may also occur during pregnancy loss, either miscarriage or pregnancy termination. Because nearly half of all pregnancies end in loss, we recently investigated the magnitude of fetal cell transfer during pregnancy loss and whether obstetric clinical factors impacted cell transfer. Prospective measurement of fetal cellular microchimerism before and after miscarriage and termination of pregnancy demonstrated a significant transfer of fetal cells in these pregnancies, with higher concentrations of fetal microchimerism in pregnancy termination vs. miscarriage and in those that were managed surgically vs. medically. The frequency of pregnancy loss as a proportion of all pregnancies, and the overrepresentation of fetal genetic abnormalities in pregnancy loss suggest that the resultant acquisition of fetal microchimerism could have a unique and substantial impact on women's health. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 4","pages":"136-8"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.24915","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31469514","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: 2013-11-18DOI: 10.4161/chim.27168
Astrid G S van Halteren, Peter Sedlmayr, Thomas Kroneis, William J Burlingham, J Lee Nelson
{"title":"Meeting report of the First Symposium on Chimerism.","authors":"Astrid G S van Halteren, Peter Sedlmayr, Thomas Kroneis, William J Burlingham, J Lee Nelson","doi":"10.4161/chim.27168","DOIUrl":"https://doi.org/10.4161/chim.27168","url":null,"abstract":"The incidence and potentially different biological impact of naturally acquired maternal and fetal cells were enthusiastically and extensively discussed when basic scientists and clinicians met at the Medical University of Graz in Austria for an International Symposium on Chimerism (Fig. 1). The two day program featured presentations by speakers from 4 different continents, intermingled with short presentations focusing on technical aspects of chimerism analysis by representatives from the companies who sponsored the meeting. Details on the program and speakers list are available at the meeting’s website (http://chimerism.medunigraz.at/cms/website.php). As also exemplified by the various different types of studies published in the recently released journal Chimerism, this field is slowly but steadily expanding as new research teams working outside and within the transplantation field have become interested in the biologically intriguing phenomena of chimerism and microchimerism (Mc). The highlights of the meeting are summarized in this meeting report. \u0000 \u0000 \u0000 \u0000Figure 1. The Symposium on Chimerism. Photo courtesy of Harry Schiffer, Copyright Graz Tourism. \u0000 \u0000 \u0000 \u0000 \u0000Technical Aspects of Chimerism Analysis \u0000Since the 1979 paper by Herzenberg and colleagues reporting enrichment of cells from pregnant women presumed to be fetal using flow-sorting techniques,1 many different studies have been published describing fetal or maternal cells in diverse hematopoietic cell types or tissues and organs. During the past decade, major technical improvements regarding the detection of these generally rare cells have been made. This has resulted in a shift from the more traditional XY fluorescent in situ hybridization (FISH) staining technique applied to tissue sections to more refined technologies such as real-time PCR for the detection of male-specific DNA sequences in genomic DNA extracted from peripheral blood cells or processed tissues. Real-time PCR reactions for mismatched HLA alleles as well as for other genetic markers (insertion/deletion) have been developed in the laboratories of meeting participants Dr Nelson (Fred Hutchinson Cancer Research Center, Seattle, USA), Dr Lambert (INSERM UMRs 1097, Marseille, France) and Dr van Halteren (Leiden University Medical Center, Leiden, the Netherlands). Unfortunately, many researchers are faced by the problem that this approach requires the availability of DNA from mother or offspring in order to find informative genetic markers. Of note, the newly developed QuantiChimera platform established at the laboratory of Dr Lambert can be contacted for technical support regarding state-of-the art PCR technology for Mc detection. \u0000 \u0000Particularly relevant for investigators who are restricted to using FISH techniques for the identification of rare maternal or fetal chimeric cells is the collective observation that this technique does not always give consistent staining results. This may be explained by the fact that archived tis","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 4","pages":"132-5"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.27168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31877900","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: 2013-05-20DOI: 10.4161/chim.25055
Trees Lepez, Mado Vandewoestyne, Dieter Deforce
{"title":"Fetal microchimeric cells in autoimmune thyroid diseases: harmful, beneficial or innocent for the thyroid gland?","authors":"Trees Lepez, Mado Vandewoestyne, Dieter Deforce","doi":"10.4161/chim.25055","DOIUrl":"https://doi.org/10.4161/chim.25055","url":null,"abstract":"<p><p>Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 4","pages":"111-8"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.25055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31469513","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: 2013-11-06DOI: 10.4161/chim.26912
Patricia A R Brunker
{"title":"Chimerism in transfusion medicine: the grandmother effect revisited.","authors":"Patricia A R Brunker","doi":"10.4161/chim.26912","DOIUrl":"10.4161/chim.26912","url":null,"abstract":"<p><p>Transfusion therapy is complicated by the production of alloantibodies to antigens present in the donor and lacking in the recipient through the poorly-understood but likely multi-factorial process of alloimmunization. The low prevalence of alloimmunization in transfused patients (6.1%) (1) suggests that processes central to immunologic tolerance may be operating in the vast majority of transfused patients who do not produce alloantibodies. Using RhD as a prototype, evidence is reviewed that the ability to make antibodies to red blood cell (RBC) antigens may result in part from immunologic tolerance acquired in utero. These ideas are extended to other examples of maternal microchimerism (MMc) of other non-inherited maternal antigens (NIMA). An evolutionary argument is offered that multi-generational immunity supports the hypothesis that MMc may partly explain the \"non-responder\" phenotype in RBC alloimmunization. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 4","pages":"119-25"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.26912","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31837590","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: 2013-11-15DOI: 10.4161/chim.27095
Peter Geck
{"title":"Symptotic detection of chimerism: Y does it matter?","authors":"Peter Geck","doi":"10.4161/chim.27095","DOIUrl":"https://doi.org/10.4161/chim.27095","url":null,"abstract":"<p><p>Microchimerism (MC), transplacental acquisition of allogeneic cells from the mother (maternofetal MC) or from the fetus (fetomaternal MC) has been in the focus of research recently. Amplicons using Y-chromosome specific SRY and DYS14 sequences have been used as markers to trace cells from a male fetus in the mother. The sensitivity of these markers in formaldehyde fixed paraffin embedded samples, however, is less than optimal. To study chimerism in breast cancer we took advantage of the evolutionary history of the Y chromosome and designed amplicons on gene repeats to generate additive PCR signals. The increased sensitivity detected high incidence of male chimerism in normal breast tissues. We also showed correlation with protection from cancer with unique quantitative biology. Accumulating data from biology and medicine indicate that natural chimerism is astonishingly frequent and may affect human conditions. We hypothesize that it has significant evolutionary ramifications as well. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 4","pages":"144-6"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.27095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31872837","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: 2013-10-11DOI: 10.4161/chim.26648
Ian M Rogers
{"title":"Trogocytosis in allogeneic transplants: donor cells take on the recipients identity.","authors":"Ian M Rogers","doi":"10.4161/chim.26648","DOIUrl":"https://doi.org/10.4161/chim.26648","url":null,"abstract":"<p><p>Trogocytosis has been identified as a mechanism of cell communication between immune cells. Unlike the more common receptor-ligand signaling, trogocytosis results in the transfer of intact and functional surface proteins between cells. For example, antigen presenting cells in contact with T cells exchange proteins which results in the T-cell acquiring antigen presentation capabilities. This allows for the newly activated T cells to stimulate other T cells thus amplifying the immune response. We have recently demonstrated that during allogeneic hematopoietic stem cell transplantation the donor cells obtain recipient MHC class I proteins by trogocytosis. The effect is a donor cell that can masquerade as a recipient cells and evade detection by NK cells and macrophages. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 4","pages":"142-3"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.26648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31805058","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: 2013-10-11DOI: 10.4161/chim.26666
Amir M Alhajjat, Beverly S Strong, Emily T Durkin, Lucas E Turner, Ram K Wadhwani, Emily F Midura, Sundeep G Keswani, Aimen F Shaaban
{"title":"Trogocytosis as a mechanistic link between chimerism and prenatal tolerance.","authors":"Amir M Alhajjat, Beverly S Strong, Emily T Durkin, Lucas E Turner, Ram K Wadhwani, Emily F Midura, Sundeep G Keswani, Aimen F Shaaban","doi":"10.4161/chim.26666","DOIUrl":"https://doi.org/10.4161/chim.26666","url":null,"abstract":"<p><p>In utero hematopoietic cellular transplantation (IUHCT) holds great promise for the treatment of congenital diseases of cellular dysfunction such as sickle cell disease, immunodeficiency disorders and inherited metabolic disorders. However, repeated failures in clinical cases of IUHCT that do not involve an immunodeficiency disease force a closer examination of the fetal immune system. While the mechanisms regulating T cell tolerance have been previously studied, the educational mechanisms leading to NK cell tolerance in prenatal chimeras remain unknown. As a low level of donor cells (1.8%) is required to induce and maintain this tolerance, it is likely that these mechanisms employ indirect host-donor interaction. This report examines donor-to-host MHC transfer (trogocytosis) as an intrinsic mechanism regulating the development and maintenance of NK cell tolerance in prenatal chimeras. The findings demonstrate that phenotypically tolerant host NK cells express low levels of transferred donor MHC antigens during development and later as mature cytotoxic lymphocytes. Further study is needed to understand how the cis-recognition of transferred donor MHC ligand influences the selection and maintenance of tolerant NK cells in prenatal chimeras. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 4","pages":"126-31"},"PeriodicalIF":0.0,"publicationDate":"2013-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.26666","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31805060","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}
{"title":"Five-year clinical effects of donor bone marrow cells infusions in kidney allograft recipients: improved graft function and higher graft survival.","authors":"Ghasem Solgi, Vijayakrishna Gadi, Biswajit Paul, Joannis Mytilineos, Gholamreza Pourmand, Abdolrasoul Mehrsai, Moslem Ranjbar, Mousa Mohammadnia, Behrouz Nikbin, Ali Akbar Amirzargar","doi":"10.4161/chim.24719","DOIUrl":"https://doi.org/10.4161/chim.24719","url":null,"abstract":"<p><p>Augmentation of microchimerism in solid organ transplant recipients by donor bone marrow cells (DBMC) infusion may promote immune hyporesponsiveness and consequently improve long-term allograft survival. Between March 2005 and July 2007, outcomes for 20 living unrelated donor (LURD) primary kidney recipients with concurrent DBMC infusion (an average of 2.19 ± 1.13 x 10⁹ donor cells consisting of 2.66 ± 1.70 x 10⁷ CD34⁺ cells) were prospectively compared with 20 non-infused control allograft recipients given similar conventional immunosuppressive regimens. With five years of clinical follow up, a total of 11 cases experienced rejection episodes (3 DBMI patients vs. 8 controls, p = 0.15). One DBMC-infused patient experienced chronic rejection vs. two episodes (1 biopsy-confirmed) in the control patients. Actuarial and death-censored 5-y graft survival was significantly higher in infused patients compared with controls (p = 0.01 and p = 0.03, respectively). Long-term graft survival was significantly associated with pre-transplant anti-HLA antibodies (p = 0.01), slightly with peripheral microchimerism (p = 0.09) and CD4⁺CD25⁺FoxP3⁺ T cells (p = 0.09). Immunosuppressant dosing was lower in infused patients than controls, particularly for mycophenolate mofetil (p = 0.001). The current findings as well as our previous reports on these patients indicates clinical improvement in long-term graft survival of renal transplant patients resulting from low-dose DBMC infusion given without induction therapy.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 3","pages":"87-94"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.24719","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31495374","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 : 2013-07-01DOI: 10.4161/chim.26155
W. Burlingham
{"title":"Transplantation immunology","authors":"W. Burlingham","doi":"10.4161/chim.26155","DOIUrl":"https://doi.org/10.4161/chim.26155","url":null,"abstract":"This Special Focus on Transplantation Immunology issue of Chimerism features papers focusing on the role of chimerism in transplantation immunology. The field of immunologic tolerance, which owes its origins to an experiment of nature resulting in hematopoetic mixed chimerism, is the subject of our featured Forum article—a debate between Jeff Mold and Colin Anderson on the implications for tolerance of the layered development of the human immune system (p. 62). Jeff argues that different species (e.g., mice vs. humans) have different solutions to achieve tolerance, with a preponderance of Treg in fetal life being critical for primates, while Colin considers the primary rules for tolerance are instead conserved and argues for the primacy of central tolerance. The impact of fetal chimerism resulting from pregnancy on the outcome of organ transplantation in women of childbearing age is the subject of a Cutting Edge View Transplantation immunology","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 1","pages":"61 - 61"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.26155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70620999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChimerismPub Date : 2013-07-01Epub Date: 2013-06-20DOI: 10.4161/chim.25400
David George, Juliann Czech, Bobby John, Min Yu, Lawrence J Jennings
{"title":"Detection and quantification of chimerism by droplet digital PCR.","authors":"David George, Juliann Czech, Bobby John, Min Yu, Lawrence J Jennings","doi":"10.4161/chim.25400","DOIUrl":"https://doi.org/10.4161/chim.25400","url":null,"abstract":"<p><p>Accurate quantification of chimerism and microchimerism is proving to be increasingly valuable for hematopoietic cell transplantation as well as non-transplant conditions. However, methods that are available to quantify low-level chimerism lack accuracy. Therefore, we developed and validated a method for quantifying chimerism based on digital PCR technology. We demonstrate accurate quantification that far exceeds what is possible with analog qPCR down to 0.01% with the potential to go even lower. Also, this method is inherently more informative than qPCR. We expect the advantages of digital PCR will make it the preferred method for chimerism analysis. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 3","pages":"102-8"},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.25400","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31682151","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}