Database : MEDLINE
Search on : Severe and Combined and Immunodeficiency [Words]
References found : 8194 [refine]
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[PMID]: 29522649
[Au] Autor:Zhu F; Hu Y
[Ad] Address:Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, 21701, Maryland, USA.
[Ti] Title:Integrity of IKK/NF-κB Shields Thymic Stroma That Suppresses Susceptibility to Autoimmunity, Fungal Infection, and Carcinogenesis.
[So] Source:Bioessays;, 2018 Mar 09.
[Is] ISSN:1521-1878
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:A pathogenic connection between autoreactive T cells, fungal infection, and carcinogenesis has been demonstrated in studies of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) as well as in a mouse model in which kinase-dead Ikkα knock-in mice develop impaired central tolerance, autoreactive T cell-mediated autoimmunity, chronic fungal infection, and esophageal squamous cell carcinoma, which recapitulates APECED. IκB kinase α (IKKα) is one subunit of the IKK complex required for NF-κB activation. IKK/NF-κB is essential for central tolerance establishment by regulating the development of medullary thymic epithelial cells (mTECs) that facilitate the deletion of autoreactive T cells in the thymus. In this review, we extensively discuss the pathogenic roles of inborn errors in the IKK/NF-κB loci in the phenotypically related diseases APECED, immune deficiency syndrome, and severe combined immunodeficiency; differentiate how IKK/NF-κB components, through mTEC (stroma), T cells/leukocytes, or epithelial cells, contribute to the pathogenesis of infectious diseases, autoimmunity, and cancer; and highlight the medical significance of IKK/NF-κB in these diseases.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1002/bies.201700131

  2 / 8194 MEDLINE  
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[PMID]: 29519870
[Au] Autor:Trentin L; Queudeville M; Eckhoff SM; Hasan MN; Münch V; Boldrin E; Seyfried F; Enzenmüller S; Debatin KM; Meyer LH
[Ad] Address:Ulm University Medical Center, Dpt. Pediatrics and Adolescent Medicine, Ulm, Germany.
[Ti] Title:Leukemia reconstitution in vivo is driven by cells in early cell cycle and low metabolic state.
[So] Source:Haematologica;, 2018 Mar 08.
[Is] ISSN:1592-8721
[Cp] Country of publication:Italy
[La] Language:eng
[Ab] Abstract:In contrast to well-established hierarchical concepts of tumor stem cells, leukemia-initiating cells in B-cell precursor acute lymphoblastic leukemia have not yet been phenotypically identified. Different subpopulations as defined by surface markers have shown equal abilities to reconstitute leukemia upon transplantation onto immunodeficient mice. Using a non-obese diabetes/severe combined immunodeficiency human acute lymphoblastic leukemia mouse model and cell cycle analysis annotating cells to distinct cycle phases, we have functionally characterized leukemia-initiating cells and found that cells in all cell cycle stages are able to reconstitute leukemia in vivo, with early cycling cells (G1blow population) exhibiting the highest leukemia-initiating potential. Interestingly, cells of the G2/M compartment, i.e. dividing cells, were less effective in leukemia reconstitution. Moreover, G1blow cells were more resistant to spontaneous or drug-induced cell death in vitro, were enriched for stem cell signatures and were less metabolically active as determined by lower reactive oxygen species levels compared to G2/M stage cells. Our data provide new information on biological properties of leukemia-initiating cells in B cell precursor acute lymphoblastic leukemia and underline the concept of a stochastic model of leukemogenesis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher

  3 / 8194 MEDLINE  
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[PMID]: 29518828
[Au] Autor:Yu G; Wang WJ; Liu DR; Tao ZF; Hui XY; Hou J; Sun JQ; Wang XC
[Ad] Address:Department of Clinical Immunology, Children's Hospital of Fudan University, Shanghai 201102, China.
[Ti] Title:[Clinical characteristics of human recombination activating gene 1 mutations in 8 immunodeficiency patients with diverse phenotypes].
[So] Source:Zhonghua Er Ke Za Zhi;56(3):186-191, 2018 Mar 02.
[Is] ISSN:0578-1310
[Cp] Country of publication:China
[La] Language:chi
[Ab] Abstract:To investigate the clinical characteristics of 8 immunodeficiency cases caused by human recombination activating gene 1 (RAG1) mutations, and to explore the relationship among genotypes, clinical manifestations and immunophenotypes. Clinical data were collected and analyzed from patients with RAG1 mutations who visited the Department of Clinical Immunology, Children's Hospital of Fudan University between October 2013 and June 2017. The data included clinical manifestations, immunophenotypes and genotypes. A total of 8 patients were diagnosed with RAG1 deficiency (6 boys and 2 girls). The minimum age of onset was 2 months, and the maximum age was 4 months. The minimum age of diagnosis was 2 months, and the maximum age was 13 years. Four patients had a family history of infant death due to severe infections. Two cases were born to the same consanguineous parents. All cases had recurrent infections, including involvement of respiratory tract (8 cases), digestive tract (6 cases), urinary tract (1 case), and central nervous system (1 case). The pathogens of infection included bacteria, viruses and fungi. Rotavirus was found in 3 cases, cytomegalovirus (CMV) in 5 cases, bacillus Calmette-Guérin adverse reaction in 2 cases (1 of whom had a positive acid-fast smear from lymph node puncture fluid), fungal infection in 3 cases. One case had multiple nodular space-occupying lesions in lungs and abdominal cavity complicated with multiple bone destruction. The peripheral blood lymphocyte counts of all patients ranged between 0.1 ×10(9)/L and 3.3×10(9)/L (median, 0.65×10(9)/L). Eosinophilia was found in 3 cases (range, (0.48-1.69) ×10(9)/L). The patients were classified according to immunophenotype as severe combined immunodeficiency phenotype (4 cases), leaky severe combined immunodeficiency (2 cases), Omenn syndrome (1 case) and combined immunodeficiency (1 case) . Decreased serum IgG levels were found in 3 cases, increased serum IgM levels in 3 cases, increased serum IgE levels in 5 cases. RAG1 homozygous mutations were detected in 5 cases and RAG1 compound heterozygous mutations in 3 cases. Two novel mutations and six previously reported mutations were identified. Three cases were successfully treated with hematopoietic stem cell transplantation. Four cases died due to infections, and the 13 year-old patient was still under follow-up in the outpatient clinic. Different RAG1 gene mutations can lead to diverse clinical presentations and immune phenotypes. Clinicians should pay attention to the family history of infant death with severe infection. In that situation, immunological evaluation and gene detection should be performed as early as possible.
[Pt] Publication type:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process
[do] DOI:10.3760/cma.j.issn.0578-1310.2018.03.007

  4 / 8194 MEDLINE  
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[PMID]: 29433935
[Au] Autor:Cicalese MP; Ferrua F; Castagnaro L; Rolfe K; De Boever E; Reinhardt RR; Appleby J; Roncarolo MG; Aiuti A
[Ad] Address:San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy, 20132; Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy, 20132.
[Ti] Title:Gene Therapy for Adenosine Deaminase Deficiency: A Comprehensive Evaluation of Short- and Medium-Term Safety.
[So] Source:Mol Ther;26(3):917-931, 2018 Mar 07.
[Is] ISSN:1525-0024
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Loss of adenosine deaminase activity leads to severe combined immunodeficiency (ADA-SCID); production and function of T, B, and natural killer (NK) cells are impaired. Gene therapy (GT) with an autologous CD34 -enriched cell fraction that contains CD34 cells transduced with a retroviral vector encoding the human ADA cDNA sequence leads to immune reconstitution in most patients. Here, we report short- and medium-term safety analyses from 18 patients enrolled as part of single-arm, open-label studies or compassionate use programs. Survival was 100% with a median of 6.9 years follow-up (range, 2.3 to 13.4 years). Adverse events were mostly grade 1 or grade 2 and were reported by all 18 patients following GT. Thirty-nine serious adverse events (SAEs) were reported by 15 of 18 patients; no SAEs were considered related to GT. The most common adverse events reported post-GT include upper respiratory tract infection, gastroenteritis, rhinitis, bronchitis, oral candidiasis, cough, neutropenia, diarrhea, and pyrexia. Incidence rates for all of these events were highest during pre-treatment, treatment, and/or 3-month follow-up and then declined over medium-term follow-up. GT did not impact the incidence of neurologic/hearing impairments. No event indicative of leukemic transformation was reported.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review

  5 / 8194 MEDLINE  
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[PMID]: 29505141
[Au] Autor:Fullerton BS; Velazco CS; Hong CR; Carey AN; Jaksic T
[Ad] Address:Center for Advanced Intestinal Rehabilitation, Boston Children's Hospital, Boston, MA, USA.
[Ti] Title:High Rates of Positive Severe Combined Immunodeficiency Screening Among Newborns with Severe Intestinal Failure.
[So] Source:JPEN J Parenter Enteral Nutr;42(1):239-246, 2018 Jan.
[Is] ISSN:1941-2444
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: Severe combined immunodeficiency (SCID) screening by T-cell receptor excision circles (TREC) has been part of Massachusetts routine newborn screening since 2009. Tetratricopeptide repeat domain 7A gene (TTC7A) mutations responsible for hereditary multiple intestinal atresia with combined immunodeficiency (MIA-CID) were also recently identified. We reviewed newborn SCID screening among infants with intestinal failure and correlated results with patient characteristics and outcomes. METHODS: Records of infants with severe intestinal failure and available newborn screen results treated at a single center 2009-2016 were reviewed retrospectively. Patients with 1 or more positive SCID screens (<252 TREC copies/µL) were compared with those without positive screens. TREC copies/µL were compared with population norms. RESULTS: Of 70 included infants, 34% had newborn screens with TREC <252 copies/µL, compared with 0.3% of the general population; TREC levels for the cohort were lower than the general population (p<0.001). Of those with positive screens, 42% had prior or subsequent negative screening, 8% had no further workup, and 50% had flow cytometry showing: severe T-cell lymphopenia (absolute CD3+ <1500 cells/mcL) in 8, 3 of whom had TTC7A mutation-associated MIA-CID. Four had CD3+ >1500 cells/mcL. MIA-CID patients had the lowest serum citrulline in the cohort; 4 of the 8 patients with CD3+ <1500 cells/mcL on flow cytometry had newborn screening notable for severe hypocitrullinemia (<3 µM). CONCLUSION: Infants with intestinal failure have lower TREC copies/µL than the general population; one-third had levels concerning for SCID, and 11% were diagnosed with severe T-cell lymphopenia. The clinical implications and etiology of this phenomenon remain unknown, but may be related to hypocitrullinemia.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Data-Review
[do] DOI:10.1002/jpen.1013

  6 / 8194 MEDLINE  
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[PMID]: 29462620
[Au] Autor:Oshima K; Saiki N; Tanaka M; Imamura H; Niwa A; Tanimura A; Nagahashi A; Hirayama A; Okita K; Hotta A; Kitayama S; Osawa M; Kaneko S; Watanabe A; Asaka I; Fujibuchi W; Imai K; Yabe H; Kamachi Y; Hara J; Kojima S; Tomita M; Soga T; Noma T; Nonoyama S; Nakahata T; Saito MK
[Ad] Address:Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Kyoto, 6068507, Japan.
[Ti] Title:Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors.
[So] Source:Biochem Biophys Res Commun;497(2):719-725, 2018 Mar 04.
[Is] ISSN:1090-2104
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:AK2 is an adenylate phosphotransferase that localizes at the intermembrane spaces of the mitochondria, and its mutations cause a severe combined immunodeficiency with neutrophil maturation arrest named reticular dysgenesis (RD). Although the dysfunction of hematopoietic stem cells (HSCs) has been implicated, earlier developmental events that affect the fate of HSCs and/or hematopoietic progenitors have not been reported. Here, we used RD-patient-derived induced pluripotent stem cells (iPSCs) as a model of AK2-deficient human cells. Hematopoietic differentiation from RD-iPSCs was profoundly impaired. RD-iPSC-derived hemoangiogenic progenitor cells (HAPCs) showed decreased ATP distribution in the nucleus and altered global transcriptional profiles. Thus, AK2 has a stage-specific role in maintaining the ATP supply to the nucleus during hematopoietic differentiation, which affects the transcriptional profiles necessary for controlling the fate of multipotential HAPCs. Our data suggest that maintaining the appropriate energy level of each organelle by the intracellular redistribution of ATP is important for controlling the fate of progenitor cells.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Data-Review

  7 / 8194 MEDLINE  
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[PMID]: 29458172
[Au] Autor:Praud C; Vauchez K; Zongo P; Vilquin JT
[Ad] Address:BOA, INRA, Université de Tours, F-37380 Nouzilly, France. Electronic address: christophe.praud@inra.fr.
[Ti] Title:Modelling human myoblasts survival upon xenotransplantation into immunodeficient mouse muscle.
[So] Source:Exp Cell Res;364(2):217-223, 2018 Mar 15.
[Is] ISSN:1090-2422
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Cell transplantation has been challenged in several clinical indications of genetic or acquired muscular diseases, but therapeutic success were mitigated. To understand and improve the yields of tissue regeneration, we aimed at modelling the fate of CD56-positive human myoblasts after transplantation. Using immunodeficient severe combined immunodeficiency (SCID) mice as recipients, we assessed the survival, integration and satellite cell niche occupancy of human myoblasts by a triple immunohistochemical labelling of laminin, dystrophin and human lamin A/C. The counts were integrated into a classical mathematical decline equation. After injection, human cells were essentially located in the endomysium, then they disappeared progressively from D0 to D28. The final number of integrated human nuclei was grossly determined at D2 after injection, suggesting that no more efficient fusion between donor myoblasts and host fibers occurs after the resolution of the local damages created by needle insertion. Almost 1% of implanted human cells occupied a satellite-like cell niche. Our mathematical model validated by histological counting provided a reliable quantitative estimate of human myoblast survival and/or incorporation into SCID muscle fibers. Informations brought by histological labelling and this mathematical model are complementary.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180304
[Lr] Last revision date:180304
[St] Status:In-Data-Review

  8 / 8194 MEDLINE  
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[PMID]: 29432734
[Au] Autor:Hu X; Wang Z; Chen M; Chen X; Liang W
[Ad] Address:Department of Orthopaedics, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China.
[Ti] Title:The anti-osteosarcoma cell activity by a mTORC1/2 dual inhibitor RES-529.
[So] Source:Biochem Biophys Res Commun;497(2):499-505, 2018 Mar 04.
[Is] ISSN:1090-2104
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:mTOR over-activation is important for human osteosarcoma (OS) tumorigenesis and progression. RES-529 is a mTORC1/2 dual inhibitor. Here, our results show that RES-529 inhibited viability, cell cycle progression and proliferation of the established (U2OS line) and primary human OS cells. RES-529 induced apoptosis activation in OS cells. It was yet non-cytotoxic to OB-6 osteoblastic cells and the primary human osteoblasts. RES-529 disrupted assembling of mTORC1 (mTOR-Raptor association) and mTORC2 (mTOR-Rictor-mLST8 association) in human OS cells, blocking mTORC1/2 activation. Significantly, RES-529 induced reactive oxygen species (ROS) production and mitochondrial depolarization in U2OS cells as well. RES-529-induced anti-OS cell activity was more potent than other known Akt-mTOR inhibitors. In vivo, RES-529 intraperitoneal injection significantly inhibited U2OS xenograft tumor growth in severe combined immunodeficiency (SCID) mice. mTORC1/2 activation in RES-529-treated tumor tissues was largely inhibited. Collectively, the mTOR inhibitor RES-529 efficiently inhibits human OS cell growth in vitro and in vivo.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Data-Review

  9 / 8194 MEDLINE  
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[PMID]: 29500792
[Au] Autor:Brevini TAL; Pennarossa G; Manzoni EFM; Gandolfi F
[Ad] Address:Laboratory of Biomedical Embryology, Department of Health, Animal Science and Food Safety and Center for Stem Cell Research, Università degli Studi di Milano, Milan, Italy. tiziana.brevini@unimi.it.
[Ti] Title:Safety and Efficacy of Epigenetically Converted Human Fibroblasts Into Insulin-Secreting Cells: A Preclinical Study.
[So] Source:Adv Exp Med Biol;, 2018 Mar 03.
[Is] ISSN:0065-2598
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Type 1 Diabetes Mellitus (T1DM) is a chronic disease that leads to loss of insulin secreting ß-cells, causing high levels of blood glucose. Exogenous insulin administration is not sufficient to mimic the normal function of ß-cells and, consequently, diabetes mellitus often progresses and can lead to major chronic complications and morbidity. The physiological control of glucose levels can only be restored by replacing the ß-cell mass.We recently developed a new strategy that allows for epigenetic conversion of dermal fibroblasts into insulin-secreting cells (EpiCC), using a brief exposure to the demethylating agent 5-aza-cytidine (5-aza-CR), followed by a pancreatic induction protocol. This method has notable advantages compared to the alternative available procedures and may represent a promising tool for clinical translation as a therapy for T1DM. However, a thought evaluation of its therapeutic safety and efficacy is mandatory to support preclinical studies based on EpiCC treatment.We here report the data obtained using human fibroblasts isolated from diabetic and healthy individuals, belonging the two genders. EpiCC were injected into 650 diabetic severe combined immunodeficiency (SCID) mice and demonstrated to be able to restore and maintain glycemic levels within the physiological range. Cells had the ability to self-regulate and not to cause hypoglycemia, when transplanted in healthy animals. Efficacy tests showed that EpiCC successfully re-established normoglycemia in diabetic mice, using a dose range that appeared clinically relevant to the concentration 0.6 × 10 EpiCC. Necropsy and histopathological investigations demonstrated the absence of malignant transformation and cell migration to organs and lymph nodes.The present preclinical study demonstrates safety and efficacy of human EpiCC in diabetic mice and supports the use of epigenetic converted cells for regenerative medicine of diabetes mellitus.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180303
[Lr] Last revision date:180303
[St] Status:Publisher
[do] DOI:10.1007/5584_2018_172

  10 / 8194 MEDLINE  
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[PMID]: 29219174
[Au] Autor:Deng M; Luo K; Hou T; Luo F; Xie Z; Zhang Z; Yang A; Yu B; Yi S; Tan J; Dong S; Xu J
[Ad] Address:National and Regional United Engineering Lab of Tissue Engineering, Department of Orthopaedics, Southwest Hospital, The Third Military Medical University, Chongqing, China.
[Ti] Title:IGFBP3 deposited in the human umbilical cord mesenchymal stem cell-secreted extracellular matrix promotes bone formation.
[So] Source:J Cell Physiol;, 2017 Dec 08.
[Is] ISSN:1097-4652
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The extracellular matrix (ECM) contains rich biological cues for cell recruitment, proliferationm, and even differentiation. The osteoinductive potential of scaffolds could be enhanced through human bone marrow mesenchymal stem cell (hBMSC) directly depositing ECM on surface of scaffolds. However, the role and mechanism of human umbilical cord mesenchymal stem cells (hUCMSC)-secreted ECM in bone formation remain unknown. We tested the osteoinductive properties of a hUCMSC-secreted ECM construct (hUCMSC-ECM) in a large femur defect of a severe combined immunodeficiency (SCID) mouse model. The hUCMSC-ECM improved the colonization of endogenous MSCs and bone regeneration, similar to the hUCMSC-seeded scaffold and superior to the scaffold substrate. Besides, the hUCMSC-ECM enhanced the promigratory molecular expressions of the homing cells, including CCR2 and TßRI. Furthermore, the hUCMSC-ECM increased the number of migrated MSCs by nearly 3.3 ± 0.1-fold, relative to the scaffold substrate. As the most abundant cytokine deposited in the hUCMSC-ECM, insulin-like growth factor binding protein 3 (IGFBP3) promoted hBMSC migration in the TßRI/II- and CCR2-dependent mechanisms. The hUCMSC-ECM integrating shRNA-mediated silencing of Igfbp3 that down-regulated IGFBP3 expression by approximately 60%, reduced the number of migrated hBMSCs by 47%. In vivo, the hUCMSC-ECM recruited 10-fold more endogenous MSCs to initiate bone formation compared to the scaffold substrate. The knock-down of Igfbp3 in the hUCMSC-ECM inhibited nearly 60% of MSC homing and bone regeneration capacity. This research demonstrates that IGFBP3 is an important MSC homing molecule and the therapeutic potential of hUCMSC-ECM in bone regeneration is enhanced by improving MSC homing in an IGFBP3-dependent mechanism.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180301
[Lr] Last revision date:180301
[St] Status:Publisher
[do] DOI:10.1002/jcp.26342


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