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[PMID]:28457419
[Au] Autor:Clemente I; Goncalo A; Faria C; Dias M; Barbosa I; Mendes C
[Ad] Endereço:Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
[Ti] Título:Relevance of Chimerism Analysis After Allogeneic Stem Cell Transplantation.
[So] Source:Transplant Proc;49(4):890-892, 2017 May.
[Is] ISSN:1873-2623
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hematopoietic stem cell transplantation is a potentially curative therapy for a range of malignant and non-malignant hematological diseases. Analysis of chimerism following allogeneic stem cell transplantation has been a routine method for the assessment of engraftment and early detection of graft failure. Lineage-specific chimerism monitoring is progressively used to specifically detect chimerism in one or more cell subsets, which may be undetected in assessment of the whole leukocyte population. The chimerism study in different leukocyte subpopulations increases sensitivity and specificity in the monitoring after transplantation, especially the analysis of T lymphocytes. All peripheral blood samples were separated into mononuclear cells and granulocytes by Ficoll density gradient centrifugation and T, B, and CD34+ was separated by immunomagnetic automatic cell separator. After DNA extraction, chimerism monitoring was performed using short tandem repeat by multiplex polymerase chain reaction followed by capillary electrophoresis. Quantification of chimerism was performed by determining the ratio of peak areas from donor and recipient informative short tandem repeat. Donor-recipient chimerism analysis in patients after allogeneic stem cell transplantation is a practical, feasible, and useful tool that predicts clinical outcomes and provides a guide for suitable therapeutic interventions.
[Mh] Termos MeSH primário: Quimerismo
Rejeição de Enxerto/genética
Transplante de Células-Tronco Hematopoéticas/métodos
Complicações Pós-Operatórias/genética
Quimeras de Transplante/genética
[Mh] Termos MeSH secundário: Adulto
Linhagem da Célula
Eletroforese Capilar
Estudos de Viabilidade
Feminino
Rejeição de Enxerto/diagnóstico
Seres Humanos
Contagem de Leucócitos
Masculino
Repetições de Microssatélites
Meia-Idade
Reação em Cadeia da Polimerase/métodos
Complicações Pós-Operatórias/diagnóstico
Período Pós-Operatório
Recidiva
Sensibilidade e Especificidade
Linfócitos T
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:29174320
[Au] Autor:Yakoub-Agha I; Ferrand C; Chalandon Y; Ballot C; Castilla Llorente C; Deschamps M; Gauthier J; Labalette M; Larghero J; Maheux C; Moreau AS; Varlet P; Pétillon MO; Pinturaud M; Rubio MT; Chabannon C
[Ad] Endereço:CHRU de Lille, unité d'allogreffe de CSH, maladies du sang, 59037 Lille, France; Université de Lille 2, Inserm U995, LIRIC, 59000 Lille, France.
[Ti] Título:[Prerequisite for hematopoietic cellular therapy programs to set up chimeric antigen receptor T-cell therapy (CAR T-cells): Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].
[Ti] Título:Prérequis nécessaires pour la mise en place de protocoles de recherche clinique évaluant des thérapies cellulaires et géniques par lymphocytes T dotés de récepteur chimérique à l'antigène (CAR T-cells) : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)..
[So] Source:Bull Cancer;104(12S):S43-S58, 2017 Dec.
[Is] ISSN:1769-6917
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:CAR T-cells are autologous or allogeneic human lymphocytes that are genetically engineered to express a chimeric antigen receptor targeting an antigen expressed on tumor cells such as CD19. CAR T-cells represent a new class of medicinal products, and belong to the broad category of Advanced Therapy Medicinal Products (ATMPs), as defined by EC Regulation 2007-1394. Specifically, they are categorized as gene therapy medicinal products. Although CAR T-cells are cellular therapies, the organization for manufacturing and delivery is far different from the one used to deliver hematopoietic cell grafts, for different reasons including their classification as medicinal products. Currently available clinical observations were mostly produced in the context of trials conducted either in the USA or in China. They demonstrate remarkable efficacy for patients presenting advanced or poor-prognosis hematological malignancies, however with severe side effects in a significant proportion of patients. Toxicities can and must be anticipated and dealt with in the context of a full coordination between the clinical cell therapy ward in charge of the patient, and the neighboring intensive care unit. The present workshop aimed at identifying prerequisites to be met in order for French hospitals to get efficiently organized and fulfill sponsors' expectations before initiation of clinical trials designed to investigate CAR T-cells.
[Mh] Termos MeSH primário: Neoplasias Hematológicas/imunologia
Neoplasias Hematológicas/terapia
Hospitais
Desenvolvimento de Programas
Receptores de Antígenos de Linfócitos T/imunologia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Quimerismo
França
Transplante de Células-Tronco Hematopoéticas/métodos
Seres Humanos
Sociedades Médicas
Linfócitos T/classificação
[Pt] Tipo de publicação:CONSENSUS DEVELOPMENT CONFERENCE; JOURNAL ARTICLE; PRACTICE GUIDELINE
[Nm] Nome de substância:
0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171228
[Lr] Data última revisão:
171228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


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[PMID]:29016691
[Au] Autor:Zhou W; Wan Y; Guo R; Deng M; Deng K; Wang Z; Zhang Y; Wang F
[Ad] Endereço:Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, Jiangsu, PR, China.
[Ti] Título:Generation of beta-lactoglobulin knock-out goats using CRISPR/Cas9.
[So] Source:PLoS One;12(10):e0186056, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Goat's milk, considered a substitute for cow's milk, has a high nutritional value. However, goat's milk contains various allergens, predominantly ß-lactoglobulin (BLG). In this study, we employed the CRISPR/Cas9 system to target the BLG locus in goat fibroblasts for sgRNA optimization and generate BLG knock-out goats through co-injection of Cas9 mRNA and small guide RNAs (sgRNAs) into goat embryos at the one-cell stage. We firstly tested sgRNA editing efficiencies in goat fibroblast cells, and approximately 8.00%-9.09% of the cells were modified in single sgRNA-guided targeting experiment. Among the kids, the genome-targeting efficiencies of single sgRNA were 12.5% (10 ng/µL sg1) and 0% (10 ng/µL sg2) and efficiencies of dual sgRNAs were 25.0% (25 ng/µL sg2+sg3 group) and 28.6% (50 ng/µL sg2+sg3 group). Relative expression of BLG in BLG knock-out goat mammary glands significantly (p < 0.01) decreased as well as other milk protein coding genes, such as CSN1S1, CSN1S2, CSN2, CSN3 and LALBA (p < 0.05). As expected, BLG protein had been abolished in the milk of the BLG knock-out goat. In addition, most of the targeted kids were chimeric (3/4), and their various body tissues were edited simultaneously. Our study thus provides a basis for optimizing the quality of goat milk, which can be applied to biomedical and agricultural research.
[Mh] Termos MeSH primário: Sistemas CRISPR-Cas
Deleção de Genes
Edição de Genes
Lactoglobulinas/genética
Leite/química
[Mh] Termos MeSH secundário: Alérgenos/genética
Animais
Animais Geneticamente Modificados
Complexo do Signalossomo COP9
Quimerismo
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas
Transferência Embrionária/métodos
Embrião de Mamíferos
Feminino
Fibroblastos/citologia
Fibroblastos/metabolismo
Expressão Gênica
Loci Gênicos
Cabras
Lactação/fisiologia
Lactoglobulinas/deficiência
Masculino
Microinjeções
Proteínas Nucleares/genética
Proteínas Nucleares/metabolismo
Cultura Primária de Células
Proteínas Quinases/genética
Proteínas Quinases/metabolismo
Subunidades Proteicas/genética
Subunidades Proteicas/metabolismo
RNA Guia/genética
RNA Guia/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens); 0 (Lactoglobulins); 0 (Nuclear Proteins); 0 (Protein Subunits); 0 (RNA, Guide); EC 2.7.- (Protein Kinases); EC 3.4.19.12 (COP9 Signalosome Complex)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171011
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186056


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[PMID]:28882984
[Au] Autor:Kollek M; Voigt G; Molnar C; Murad F; Bertele D; Krombholz CF; Bohler S; Labi V; Schiller S; Kunze M; Geley S; Niemeyer CM; Garcia-Saez A; Erlacher M
[Ad] Endereço:Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
[Ti] Título:Transient apoptosis inhibition in donor stem cells improves hematopoietic stem cell transplantation.
[So] Source:J Exp Med;214(10):2967-2983, 2017 Oct 02.
[Is] ISSN:1540-9538
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During hematopoietic stem cell transplantation, a substantial number of donor cells are lost because of apoptotic cell death. Transplantation-associated apoptosis is mediated mainly by the proapoptotic BCL-2 family proteins BIM and BMF, and their proapoptotic function is conserved between mouse and human stem and progenitor cells. Permanent inhibition of apoptosis in donor cells caused by the loss of these BH3-only proteins improves transplantation outcome, but recipients might be exposed to increased risk of lymphomagenesis or autoimmunity. Here, we address whether transient inhibition of apoptosis can serve as a safe but efficient alternative to improve the outcome of stem cell transplantation. We show that transient apoptosis inhibition by short-term overexpression of prosurvival BCL-XL, known to block BIM and BMF, is not only sufficient to increase the viability of hematopoietic stem and progenitor cells during engraftment but also improves transplantation outcome without signs of adverse pathologies. Hence, this strategy represents a promising and novel therapeutic approach, particularly under conditions of limited donor stem cell availability.
[Mh] Termos MeSH primário: Apoptose
Transplante de Células-Tronco Hematopoéticas/métodos
[Mh] Termos MeSH secundário: Animais
Apoptose/fisiologia
Caspases/efeitos dos fármacos
Caspases/metabolismo
Quimerismo
Seres Humanos
Leucemia/etiologia
Camundongos
Camundongos Endogâmicos C57BL
Transdução Genética
Proteína bcl-X/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bcl2l1 protein, mouse); 0 (bcl-X Protein); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE
[do] DOI:10.1084/jem.20161721


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[PMID]:28480895
[Au] Autor:Kinder JM; Stelzer IA; Arck PC; Way SS
[Ad] Endereço:Division of Infectious Disease, Cincinnati Children's Hospital.
[Ti] Título:Immunological implications of pregnancy-induced microchimerism.
[So] Source:Nat Rev Immunol;17(8):483-494, 2017 Aug.
[Is] ISSN:1474-1741
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Immunological identity is traditionally defined by genetically encoded antigens, with equal maternal and paternal contributions as a result of Mendelian inheritance. However, vertically transferred maternal cells also persist in individuals at very low levels throughout postnatal development. Reciprocally, mothers are seeded during pregnancy with genetically foreign fetal cells that persist long after parturition. Recent findings suggest that these microchimeric cells expressing non-inherited, familially relevant antigenic traits are not accidental 'souvenirs' of pregnancy, but are purposefully retained within mothers and their offspring to promote genetic fitness by improving the outcome of future pregnancies. In this Review, we discuss the immunological implications, benefits and potential consequences of individuals being constitutively chimeric with a biologically active 'microchiome' of genetically foreign cells.
[Mh] Termos MeSH primário: Tolerância Imunológica
Troca Materno-Fetal
Gravidez/imunologia
[Mh] Termos MeSH secundário: Animais
Autoimunidade
Quimerismo
Feminino
Feto/citologia
Feto/imunologia
Seres Humanos
Sistema Imunitário/citologia
Imunidade Materno-Adquirida
Memória Imunológica
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170509
[St] Status:MEDLINE
[do] DOI:10.1038/nri.2017.38


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[PMID]:28441386
[Au] Autor:Schütz E; Fischer A; Beck J; Harden M; Koch M; Wuensch T; Stockmann M; Nashan B; Kollmar O; Matthaei J; Kanzow P; Walson PD; Brockmöller J; Oellerich M
[Ad] Endereço:Chronix Biomedical, Göttingen, Germany.
[Ti] Título:Graft-derived cell-free DNA, a noninvasive early rejection and graft damage marker in liver transplantation: A prospective, observational, multicenter cohort study.
[So] Source:PLoS Med;14(4):e1002286, 2017 Apr.
[Is] ISSN:1549-1676
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Graft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, is a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional liver function tests (LTFs) nor immunosuppressive drug monitoring are very effective for rejection monitoring. We therefore hypothesized that the quantitative measurement of donor-derived cell-free DNA (cfDNA) would have independent value for the assessment of graft integrity, including damage from acute rejection. METHODS AND FINDINGS: Traditional LFTs were performed and plasma GcfDNA was monitored in 115 adults post-LTx at three German transplant centers as part of a prospective, observational, multicenter cohort trial. GcfDNA percentage (graft cfDNA/total cfDNA) was measured using droplet digital PCR (ddPCR), based on a limited number of predefined single nucleotide polymorphisms, enabling same-day turn-around. The same method was used to quantify blood microchimerism. GcfDNA was increased >50% on day 1 post-LTx, presumably from ischemia/reperfusion damage, but rapidly declined in patients without graft injury within 7 to 10 d to a median <10%, where it remained for the 1-y observation period. Of 115 patients, 107 provided samples that met preestablished criteria. In 31 samples taken from 17 patients during biopsy-proven acute rejection episodes, the percentage of GcfDNA was elevated substantially (median 29.6%, 95% CI 23.6%-41.0%) compared with that in 282 samples from 88 patients during stable periods (median 3.3%, 95% CI 2.9%-3.7%; p < 0.001). Only slightly higher values (median 5.9%, 95% CI 4.4%-10.3%) were found in 68 samples from 17 hepatitis C virus (HCV)-positive, rejection-free patients. LFTs had low overall correlations (r = 0.28-0.62) with GcfDNA and showed greater overlap between patient subgroups, especially between acute rejection and HCV+ patients. Multivariable logistic regression modeling demonstrated that GcfDNA provided additional LFT-independent information on graft integrity. Diagnostic sensitivity and specificity were 90.3% (95% CI 74.2%-98.0%) and 92.9% (95% CI 89.3%-95.6%), respectively, for GcfDNA at a threshold value of 10%. The area under the receiver operator characteristic curve was higher for GcfDNA (97.1%, 95% CI 93.4%-100%) than for same-day conventional LFTs (AST: 95.7%; ALT: 95.2%; γ-GT: 94.5%; bilirubin: 82.6%). An evaluation of microchimerism revealed that the maximum donor DNA in circulating white blood cells was only 0.068%. GcfDNA percentage can be influenced by major changes in host cfDNA (e.g., due to leukopenia or leukocytosis). One limitation of our study is that exact time-matched GcfDNA and LFT samples were not available for all patient visits. CONCLUSIONS: In this study, determination of GcfDNA in plasma by ddPCR allowed for earlier and more sensitive discrimination of acute rejection in LTx patients as compared with conventional LFTs. Potential blood microchimerism was quantitatively low and had no significant influence on GcfDNA value. Further research, which should ideally include protocol biopsies, will be needed to establish the practical value of GcfDNA measurements in the management of LTx patients.
[Mh] Termos MeSH primário: DNA/sangue
Rejeição de Enxerto/sangue
Transplante de Fígado
[Mh] Termos MeSH secundário: Adulto
Idoso
Área Sob a Curva
Biomarcadores/sangue
Quimerismo
Feminino
Alemanha
Rejeição de Enxerto/diagnóstico
Hepacivirus
Seres Humanos
Leucócitos/metabolismo
Testes de Função Hepática
Modelos Logísticos
Masculino
Meia-Idade
Estudos Prospectivos
Curva ROC
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Biomarkers); 9007-49-2 (DNA)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170609
[Lr] Data última revisão:
170609
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pmed.1002286


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[PMID]:28355720
[Au] Autor:Fu L; Wei N; Wang JS; Wu L; Wang YN; Huang DY; Liu JL; Wang Z
[Ad] Endereço:Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
[Ti] Título:[The clinical characteristics of adult hemophagocytic lymphohistiocytosis treated with haploidentical donor hematopoietic stem cell transplantation].
[So] Source:Zhonghua Nei Ke Za Zhi;56(4):273-278, 2017 Apr 01.
[Is] ISSN:0578-1426
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To analyze the clinical characteristics of adult patients with hemophagocytic lymphohistiocytosis (HLH) receiving haploidentical donor hematopoietic stem cell transplantation (HID HSCT). We retrospectively reviewed 20 adult patients with HLH from August 2009 to August 2014.The clinical features and outcome were analyzed. Conditioning regimens consisted of total body irradiation/etoposide/cyclophosphamide (TBI/VP-16/CTX) and busulfan (Bu)/VP-16/CTX in HLH with anti-thymocyte globulin (ATG) 8 mg/kg.The stem cells were mobilized from donors' peripheral blood.Median time to white blood cell engraftment was 13 (9-27) days.Median time to platelet engraftment was 14 (10-28) days.Mixed chimerism after transplantation developed in 4 patients and no patient presented graft failure.Eight patients developed grade â…¡ to â…¢ acute graft-versus-host disease (GVHD), while as chronic GVHD occurred in 9 patients.Among 12 patients with EB virus(EBV) reactivation, 2 patients developed post-transplant lymphoproliferative disorder (PTLD), 7 were suspected as PTLD and 3 were considered as relapse of primary disease.With a median follow-up of 20 months (range: 0.5-108 months) after transplantation, the estimated 2-year overall survival (OS) rate was (60.0±11.0)% in all patients.During the follow-up, 12 patients survived, 8 died including 5 within 100 days after HSCT.Among 5 non-remission patients before HSCT, 4 patients died within 100 days after HCT. HID HSCT is an effective treatment for adult patients with HLH to achieve remission and long-term survival. High proportion of mixed chimerism has been seen at early stage after transplantation.EBV reactivation and early transplant-related mortality are common.
[Mh] Termos MeSH primário: Soro Antilinfocitário/uso terapêutico
Antineoplásicos Alquilantes/uso terapêutico
Bussulfano/uso terapêutico
Ciclofosfamida/uso terapêutico
Transplante de Células-Tronco Hematopoéticas/métodos
Linfo-Histiocitose Hemofagocítica/terapia
Condicionamento Pré-Transplante/métodos
Transplante Homólogo/métodos
Irradiação Corporal Total/efeitos adversos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Soro Antilinfocitário/administração & dosagem
Antineoplásicos Alquilantes/administração & dosagem
Bussulfano/administração & dosagem
Quimerismo
Ciclofosfamida/administração & dosagem
Infecções por Vírus Epstein-Barr/etiologia
Feminino
Doença Enxerto-Hospedeiro
Herpesvirus Humano 4
Seres Humanos
Linfo-Histiocitose Hemofagocítica/mortalidade
Masculino
Período Pós-Operatório
Estudos Retrospectivos
Taxa de Sobrevida
Doadores de Tecidos
Resultado do Tratamento
Irradiação Corporal Total/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antilymphocyte Serum); 0 (Antineoplastic Agents, Alkylating); 8N3DW7272P (Cyclophosphamide); G1LN9045DK (Busulfan)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170330
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0578-1426.2017.04.007


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[PMID]:28336908
[Au] Autor:Utsumi M; Takaki A; Umeda Y; Koike K; Napier SC; Watanabe N; Shinoura S; Yoshida R; Nobuoka D; Yasunaka T; Oto T; Araki M; Yamamoto K; Fujiwara T; Yagi T
[Ad] Endereço:Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
[Ti] Título:Early Chimerism After Liver Transplantation Reflects the Clinical Course of Recurrent Hepatitis C.
[So] Source:Ann Transplant;22:156-165, 2017 Mar 24.
[Is] ISSN:2329-0358
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C. MATERIAL AND METHODS We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1-100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined. RESULTS Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism. CONCLUSIONS Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.
[Mh] Termos MeSH primário: Quimerismo
Antígenos HLA/imunologia
Hepatite C/imunologia
Falência Hepática/cirurgia
Transplante de Fígado/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Autoanticorpos
Linfócitos B/imunologia
Feminino
Citometria de Fluxo
Seres Humanos
Falência Hepática/imunologia
Masculino
Meia-Idade
Recidiva
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies); 0 (HLA Antigens)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE


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[PMID]:28332165
[Au] Autor:Jolis TW; Brucker BM; Schorl C; Butera JN; Quesenberry PJ
[Ad] Endereço:The Warren Alpert Medical School of Brown University, 35 W 74th St Apt 4R, New York, NY, 10023, USA. Timothy_jolis@alumni.brown.edu.
[Ti] Título:Low microchimeric cell density in tumors suggests alternative antineoplastic mechanism.
[So] Source:Med Oncol;34(4):65, 2017 Apr.
[Is] ISSN:1559-131X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Microchimerism has generally been shown to protect against cancer (Gilmore et al. in Exp Hematol 36(9):1073-1077, 2008). The mechanism of how this occurs is an area of intense study, as it may lead to new cancer treatments. The leading theory is that microchimeric cells perform immune surveillance by directly fighting cancerous cells and that they also act as stem cells, repairing damaged tissue (Khosrotehrani et al. in JAMA 292:75-80, 2004). However, there is conflicting evidence to support this theory. Several small studies have found few microchimeric cells in tumor tissue (Gadi in Breast Cancer Res Treat 121(1):241-244, 2010; Cirello et al. in Int J Cancer 126:2874-2878, 2010), while another study contradicted these findings by showing microchimeric cells clustered around tumor tissue (O'Donoghue et al. in Reprod Biomed Online 16:382-390, 2008). To date, we have designed the largest and broadest study to investigate this question of whether microchimeric cells really do cluster at tumor tissue. We analyzed 245 samples from a broad range of cancer types. Using PCR for the male chromosome marker TSPY1, we identified only 12 out of 245 samples with microchimerism for a rate of 4.9% (95% confidence interval 2.2-7.6%). Five of these samples were confirmed using Y fluorescence in situ hybridization. This rate of 4.9% microchimerism is the lowest reported in any study. The low percentage of microchimerism observed in our broad study suggests that microchimeric cells do not invade tumors to fight off neoplasm.
[Mh] Termos MeSH primário: Neoplasias/genética
Neoplasias/patologia
[Mh] Termos MeSH secundário: Contagem de Células
Proteínas de Ciclo Celular/genética
Quimerismo
Feminino
Seres Humanos
Hibridização in Situ Fluorescente
Neoplasias/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cell Cycle Proteins); 0 (TSPY1 protein, human)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.1007/s12032-017-0921-6


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[PMID]:28329160
[Au] Autor:Harrington WE; Kanaan SB; Muehlenbachs A; Morrison R; Stevenson P; Fried M; Duffy PE; Lee Nelson J
[Ad] Endereço:Department of Pediatrics, University of Washington School of Medicine/Seattle Children's Hospital, Washington.
[Ti] Título:Maternal Microchimerism Predicts Increased Infection but Decreased Disease due to Plasmodium falciparum During Early Childhood.
[So] Source:J Infect Dis;215(9):1445-1451, 2017 05 01.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: A mother's infection with placental malaria (PM) can affect her child's susceptibility to malaria, although the mechanism remains unclear. The fetus acquires a small amount of maternal cells and DNA known as maternal microchimerism (MMc), and we hypothesized that PM increases MMc and that MMc alters risk of Plasmodium falciparum malaria during infancy. Methods: In a nested cohort from Muheza, Tanzania, we evaluated the presence and level of cord blood MMc in offspring of women with and without PM. A maternal-specific polymorphism was identified for each maternal-infant pair, and MMc was assayed by quantitative polymerase chain reaction. The ability of MMc to predict malaria outcomes during early childhood was evaluated in longitudinal models. Results: Inflammatory PM increased the detection rate of MMc among offspring of primigravidae and secundigravidae, and both noninflammatory and inflammatory PM increased the level of MMc. Detectable MMc predicted increased risk of positive blood smear but, interestingly, decreased risk of symptomatic malaria and malaria hospitalization. Conclusions: The acquisition of MMc may result in increased malaria infection but protection from malaria disease. Future studies should be directed at the cellular component of MMc, with attention to its ability to directly or indirectly coordinate anti-malarial immune responses in the offspring.
[Mh] Termos MeSH primário: Quimerismo/estatística & dados numéricos
Suscetibilidade a Doenças
Malária Falciparum/genética
Doenças Placentárias/genética
Complicações Parasitárias na Gravidez/genética
[Mh] Termos MeSH secundário: Adulto
Pré-Escolar
Estudos de Coortes
Feminino
Hospitalização
Seres Humanos
Lactente
Recém-Nascido
Malária Falciparum/epidemiologia
Masculino
Doenças Placentárias/epidemiologia
Plasmodium falciparum
Gravidez
Complicações Parasitárias na Gravidez/epidemiologia
Prevalência
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix129



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