ChimerismPub Date : 2013-01-01DOI: 10.4161/chim.23347
Faouzi Braza, Jean Paul Soulillou, Sophie Brouard
{"title":"Reconsidering the bio-detection of tolerance in renal transplantation.","authors":"Faouzi Braza, Jean Paul Soulillou, Sophie Brouard","doi":"10.4161/chim.23347","DOIUrl":"https://doi.org/10.4161/chim.23347","url":null,"abstract":"<p><p>Operational tolerance in kidney transplantation tolerance is rare phenomenon. It concerns recipients who keep a good function of their graft without immunosuppressors for more than one year. A critical need in the field of transplantation tolerance is the identification of biomarkers able to detect precociously tolerance phenotype in stable recipient in order to adapt treatment and progressively stop immunosuppressive therapy. But many limitations in these studies slow the application in clinics of such tolerance signature. In this addendum article we talk about these limitations and potential new directions to improve our approach in the quest of tolerance biomarkers.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 1","pages":"15-7"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.23347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31462187","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 : 2013-01-01Epub Date: 2012-12-21DOI: 10.4161/chim.23348
Miranda P Dierselhuis, Els Goulmy
{"title":"We are all born as microchimera.","authors":"Miranda P Dierselhuis, Els Goulmy","doi":"10.4161/chim.23348","DOIUrl":"https://doi.org/10.4161/chim.23348","url":null,"abstract":"<p><p>It is well accepted that pregnancy establishes microchimerism. Lately, transmaternal passage of cells from elder siblings has been suggested as possible source of non-fetal microchimerism in nulliparous women. Recently, we identified both non-maternal microchimerism and minor H antigen specific cellular immune responses against these microchimeric cells in umbilical cord blood. The identification of the latter microchimeric cells from birth onwards explains the high incidence of microchimerism in healthy people and in people with different diseases. The circulating microchimeric cells of different origin can induce a wealth of antigen specific responses. Thus, nobody is born naïve: we are all microchimera's.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 1","pages":"18-9"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.23348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31143260","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 : 2013-01-01Epub Date: 2012-12-13DOI: 10.4161/chim.23158
Morris Kletzel, Wei Huang, Marie Olszewski, Sana Khan
{"title":"Validation of chimerism in pediatric recipients of allogeneic hematopoietic stem cell transplantation (HSCT) a comparison between two methods: real-time PCR (qPCR) vs. variable number tandem repeats PCR (VNTR PCR).","authors":"Morris Kletzel, Wei Huang, Marie Olszewski, Sana Khan","doi":"10.4161/chim.23158","DOIUrl":"https://doi.org/10.4161/chim.23158","url":null,"abstract":"<p><p>Post-hematopoietic stem cell transplantation (HSCT) chimerism monitoring is important to assess relapse and therapeutic intervention. The purpose of our study is to compare two methods variable number tandem repeats (VNTR) vs. quantitative real- time polymerase chain reaction (qPCR) in terms of determining chimerism. 127 (peripheral blood n=112, bone marrow n=15) samples were simultaneously tested by VNTR using APO-B, D1S80, D1S111, D17S30, gene loci SRY and ZP3 and qPCR using 34 assays (CA001-CA034) that are designed to a bi-allelic insertion/deletion (indel) polymorphism in the human genome. Samples were separated in three subsets: total WBC, T-cell and Myeloid cells. Extraction of DNA was performed then quantified. We analyzed column statistics, paired t-test and regression analysis for both methods. There was complete correlation between the two methods. The simplicity and rapidity of the test results from the qPCR method is more efficient and accurate to assess chimerism.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.23158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31118234","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 : 2013-01-01DOI: 10.4161/chim.24071
Ulrike Baranyi, Rudolf Valenta, Thomas Wekerle
{"title":"Molecular chimerism in IgE-mediated allergy: B-and T-cell tolerance toward highly immunogenic exogenous antigens.","authors":"Ulrike Baranyi, Rudolf Valenta, Thomas Wekerle","doi":"10.4161/chim.24071","DOIUrl":"10.4161/chim.24071","url":null,"abstract":"<p><p>Specific immunotherapy is the only curative treatment currently available for IgE-mediated allergy and preventive strategies are lacking altogether. We have recently reported that molecular chimerism induces durable tolerance in experimental models of allergy, thus potentially providing a new approach for the treatment and prevention of allergic diseases. Molecular chimerism is a gene-therapy approach for tolerance induction toward defined disease-causing antigens. In proof-of-concept studies, we introduced a clinically relevant grass pollen allergen into hematopoietic stem cells and transplanted those modified cells into preconditioned syngeneic mice. Long-lasting and robust tolerance toward the allergen was achieved. In our most recent studies published in Clinical and Experimental Allergy we demonstrated that milder, non-myeloablative conditioning is sufficient to induce tolerance. Our results revealed that, in contrast to other rodent models of chimerism, persistent microchimerism suffices to induce lasting tolerance at the T cell, B cell and effector cell levels in IgE-mediated allergy. This article addendum provides a summary of the recent paper and its implications.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 1","pages":"29-31"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654736/pdf/chim-4-29.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31461354","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 : 2013-01-01DOI: 10.4161/chim.24070
Xiao-Jun Huang
{"title":"Haploidentical hematopoietic stem cell transplantation without in vitro T-cell-depletion for the treatment of hematologic diseases.","authors":"Xiao-Jun Huang","doi":"10.4161/chim.24070","DOIUrl":"https://doi.org/10.4161/chim.24070","url":null,"abstract":"<p><p>Haploidentical hematopoietic stem cell transplantation (HSCT) has been accepted worldwide as an alternative treatment for patients with hematologic diseases who do not have a human leukocyte antigen (HLA) identical sibling donor or who require urgent transplantation. The results from our nine-year experience showed that granulocyte colony-stimulating factor (G-CSF) primed bone marrow (G-BM) combined with peripheral blood grafts (G-PB) from haploidentical donors, without in vitro T cell depletion (TCD), is a reliable source of stem cells for transplantation to cure acute leukemia and chronic myeloid leukemia. Recent findings confirmed that unmanipulated haploidentical HSCT is a promising protocol that can be successfully extended to treat intermediate and high-risk myelodysplastic syndrome and severe aplastic anemia. Recent observations suggest the association of improved immune recovery with better transplant outcomes after haploidentical HSCT. Chronic graft-vs.-host-disease severity strongly correlates with negative impacts on patients' health-related quality of life, suggesting that it should be successfully controlled. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 1","pages":"26-8"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.24070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31254515","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 : 2013-01-01DOI: 10.4161/chim.23350
David P Al-Adra, Colin C Anderson
{"title":"Toward minimal conditioning protocols for allogeneic chimerism in tolerance resistant recipients.","authors":"David P Al-Adra, Colin C Anderson","doi":"10.4161/chim.23350","DOIUrl":"https://doi.org/10.4161/chim.23350","url":null,"abstract":"<p><p>Mixed chimerism is a promising approach toward generating donor-specific immunological tolerance. However, chimerism induction can be toxic; therefore, there is an effort to develop non-myeloablative, minimal intensity protocols that can generate chimerism without the toxic side effects. Recently, with the goal of creating a minimalistic chimerism induction protocol in the tolerance resistant non-obese diabetic (NOD) mouse model, we identified pre-existing T cells as cells that resist fully allogeneic chimerism. With monoclonals targeting NOD T cells, we showed that long-term chimerism and tolerance toward donor islets could be established. However, this promising new protocol relied on the administration of a single dose of anti-CD40 ligand, which is not clinically applicable. In refining protocols to move even closer to clinical utility, we report here initial success at generating fully allogeneic mixed chimerism in NOD mice by adding cyclophosphamide to the conditioning regimen in place of anti-CD40 ligand antibodies. </p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 1","pages":"23-5"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.23350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31169942","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":"Combined treatment with regulatory T cells and vascularized bone marrow transplantation creates mixed chimerism and induces donor-specific tolerance to vascularized composite allografts without cytoreductive conditioning.","authors":"Jeng-Yee Lin, Feng-Chou Tsai, Christopher Glenn Wallace, Wei-Chao Huang, Fu-Chan Wei, Shuen-Kuei Liao","doi":"10.4161/chim.23349","DOIUrl":"https://doi.org/10.4161/chim.23349","url":null,"abstract":"<p><p>We demonstrate herein that combination treatment with regulatory T cells (Tregs) and vascularized bone marrow transplantation (VBMT) can achieve stable mixed chimerism and long-term transplantation tolerance to vascularized composite allografts (VCA) without requiring cytoreductive recipient conditioning in rats. An appreciable number of Tregs of recipient origin was shown at the interface between recipient and transplanted VCA tissues, implicating a significant role for Tregs in protecting VCA from rejection. This cytoreduction-free protocol using co-treatment with Tregs and VBMT warrants further investigation toward potential clinical application for VCA transplantation.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"4 1","pages":"20-2"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.23349","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31553796","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 : 2012-07-01DOI: 10.4161/chim.22277
Payam Saadai, Tippi C MacKenzie
{"title":"Increased maternal microchimerism after open fetal surgery.","authors":"Payam Saadai, Tippi C MacKenzie","doi":"10.4161/chim.22277","DOIUrl":"https://doi.org/10.4161/chim.22277","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"3 3","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2012-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.22277","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30918164","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 : 2012-07-01DOI: 10.4161/chim.22769
Stephanie Pritchard, Inga Peter, Kirby L Johnson, Diana W Bianchi
{"title":"The natural history of fetal cells in postpartum murine maternal lung and bone marrow: a two-stage phenomenon.","authors":"Stephanie Pritchard, Inga Peter, Kirby L Johnson, Diana W Bianchi","doi":"10.4161/chim.22769","DOIUrl":"https://doi.org/10.4161/chim.22769","url":null,"abstract":"<p><p>During pregnancy, fetal cells cross into the maternal organs where they reside postpartum. Evidence from multiple laboratories suggests that these microchimeric fetal cells contribute to maternal tissue repair after injury. In mouse models, most injury experiments are performed during pregnancy; however, in a clinical setting most injuries or diseases occur postpartum. Therefore, experiments using animal models should be designed to address questions in the time period following delivery. In order to provide a baseline for such experiments, we analyzed the natural history of fetal cells in the postpartum maternal organs. Female C57BL/6J mice were mated to males homozygous for the enhanced green fluorescent protein gene. Fetal cells in the maternal lungs and bone marrow were identified by their green fluorescence using in a high-speed flow cytometer and their counts were compared between the lung and bone marrow. Spearman correlation analysis was used to identify relationships between the duration of time postpartum and the cell counts and ratio of live and dead cells. Our results show that fetal cells persist in these organs until at least three months postpartum in healthy female mice. We show a two-stage decline, with an initial two and a half-week rapid clearance followed by a trend of gradual decrease. Additionally, an increase in the ratio of live to dead cells within the lung over time suggests that these cells may replicate in vivo. The results presented here will inform the design of future experiments and may have implications for women's health.</p>","PeriodicalId":89114,"journal":{"name":"Chimerism","volume":"3 3","pages":"59-64"},"PeriodicalIF":0.0,"publicationDate":"2012-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/chim.22769","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31026268","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}