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    7757 results match your criteria Severe Combined Immunodeficiency

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    A Practical Approach to Newborn Screening for Severe Combined Immunodeficiency Using the T Cell Receptor Excision Circle Assay.
    Front Immunol 2017 8;8:1470. Epub 2017 Nov 8.
    Department of Pediatrics, Division of Rheumatology, Medical College of Wisconsin, Milwaukee, WI, United States.
    Severe combined immunodeficiency (SCID) is a life-threatening condition of newborns and infants caused by defects in genes involved in T cell development. Newborn screening (NBS) for SCID using the T cell receptor excision circle (TREC) assay began in Wisconsin in 2008 and has been adopted or is being implemented by all states in 2017. It has been established that NBS using the TREC assay is extremely sensitive to detect SCID in the newborn period. Read More

    First Year of Israeli Newborn Screening for Severe Combined Immunodeficiency-Clinical Achievements and Insights.
    Front Immunol 2017 6;8:1448. Epub 2017 Nov 6.
    Pediatric Department A and the Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
    Severe combined immunodeficiency (SCID), the most severe form of T cell immunodeficiency, is detectable through quantification of T cell receptor excision circles (TRECs) in dried blood spots obtained at birth. Herein, we describe the results of the first year of the Israeli SCID newborn screening (NBS) program. This important, life-saving screening test is available at no cost for every newborn in Israel. Read More

    Production and rearing of germ-free X-SCID pigs.
    Exp Anim 2017 Nov 21. Epub 2017 Nov 21.
    Division of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University.
    Pigs with X-linked severe combined immunodeficiency (X-SCID) caused by a mutation of the interleukin-2 receptor gamma chain gene (IL2RG) are of value for a wide range of studies. However, they do not survive longer than 8 weeks because of their susceptibility to infections. To allow longer survival of X-SCID pigs, the animals must be born and reared under germ-free conditions. Read More

    Immunodeficiency in CHARGE syndrome.
    Am J Med Genet C Semin Med Genet 2017 Nov 21. Epub 2017 Nov 21.
    Department of Allergy and Immunology, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
    Immunodeficiency can occur in CHARGE syndrome, with immunophenotypes including reduction in T-cell counts, combined T-B cell defects rarely requiring antibiotic prophylaxis or immunoglobulin replacement, and severe combined immunodeficiency, which is fatal without immune reconstitution. However, the prevalence of immunodeficiency in CHARGE syndrome remains unclear with few prospective studies. In this review, we examine the existing literature covering immunodeficiency associated with CHARGE syndrome, compare these with immunodeficiencies reported in 22q11. Read More

    Treosulfan, Fludarabine Conditioning for HSCT in Children with Primary Immunodeficiency: UK Experience.
    Biol Blood Marrow Transplant 2017 Nov 16. Epub 2017 Nov 16.
    Department of Paediatric Immunology, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, UK.
    We previously published results of 70 children who received treosulfan with cyclophosphamide (30) or fludarabine (40) before haematopoietic stem cell transplantation (HSCT) for Primary Immunodeficiency (PID). Toxicity was lower and T cell chimerism better in those receiving fludarabine, but numbers were relatively small and follow-up short. We now report outcome of 160 children who received homogeneous conditioning with treosulfan, fludarabine mostly with alemtuzumab (n=124). Read More

    SCID pigs: An emerging large animal NK model.
    J Rare Dis Res Treat 2017 18;2(3):1-6. Epub 2017 Apr 18.
    Genetics and Genomics Graduate Program, Department of Animal Science, Iowa State University, Ames, IA 50011, USA.
    Severe Combined ImmunoDeficiency (SCID) is defined as the lack or impairment of an adaptive immune system. Although SCID phenotypes are characteristically absent of T and B cells, many such SCID cellular profiles include the presence of NK cells. In human SCID patients, functional NK cells may impact the engraftment success of life saving procedures such as bone marrow transplantation. Read More

    B-cell receptor repertoire sequencing in patients with primary immunodeficiency: a review.
    Immunology 2017 Nov 15. Epub 2017 Nov 15.
    Division of Immunology, University Children's Hospital Zurich, Switzerland.
    The advent of next-generation sequencing now allows a detailed assessment of the adaptive immune system in health and disease. In particular, high-throughput B-cell receptor (BCR) repertoire sequencing provides detailed information about the functionality and abnormalities of the B-cell system. However, it is mostly unknown how the BCR repertoire is altered in the context of primary immunodeficiencies (PID) and whether findings are consistent across phenotypes and genotypes. Read More

    Reduction of pluripotent gene expression in murine embryonic stem cells exposed to mechanical loading or Cyclo RGD peptide.
    BMC Cell Biol 2017 Nov 14;18(1):32. Epub 2017 Nov 14.
    McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada.
    Background: Self-renewal and differentiation of embryonic stem cells (ESCs) is directed by biological and/or physical cues that regulate multiple signaling cascades. We have previously shown that mESCs seeded in a type I collagen matrix demonstrate a loss of pluripotent marker expression and differentiate towards an osteogenic lineage. In this study, we examined if this effect was mediated in part through Arginylglycylaspartic acid (RGD) dependent integrin activity and/or mechano-transduction. Read More

    Expanding the phenotypic spectrum of TP63-related disorders including the first set of monozygotic twins.
    Am J Med Genet A 2017 Nov 12. Epub 2017 Nov 12.
    Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
    Individuals with Tumor Protein P63 (TP63)-related disorders are known to present with a range of phenotypic features, including ectrodactyly, ectodermal dysplasia, cleft lip/palate, Rapp-Hodgkin, Hay-Wells, and limb-mammary syndromes. We present six individuals from three families, including a set of monozygotic twins, with pathogenic TP63 variants who had novel clinical findings. The twins were discordant for cleft lip and palate, and the type of hand malformations, but concordant for choanal atresia, and bilateral volar nail. Read More

    The γ c family of cytokines: fine-tuning signals from IL-2 and IL-21 in the regulation of the immune response.
    F1000Res 2017 23;6:1872. Epub 2017 Oct 23.
    Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
    Interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21 form a family of cytokines based on the sharing of a receptor component, the common cytokine receptor γ chain, γ c, which is encoded by the gene mutated in humans with X-linked severe combined immunodeficiency (XSCID). Together, these cytokines play critical roles in lymphoid development, differentiation, growth, and survival as well as mediating effector function. Here, we provide an overview of the main actions of members of this cytokine family but then primarily focus on IL-2 and IL-21, discussing their dynamic interplay and contributions to a fine-tuned immune response. Read More

    Newborn Screening for Primary Immunodeficiency Diseases: History, Current and Future Practice.
    J Clin Immunol 2017 Nov 8. Epub 2017 Nov 8.
    Department of Clinical Immunology, Karolinska University Hospital Huddinge, SE-141 86, Stockholm, Sweden.
    The primary objective of population-based newborn screening is the early identification of asymptomatic infants with a range of severe diseases, for which effective treatment is available and where early diagnosis and intervention prevent serious sequelae. Primary immunodeficiency diseases (PID) are a heterogeneous group of inborn errors of immunity. Severe combined immunodeficiency (SCID) is one form of PID which is uniformly fatal without early, definitive therapy, and outcomes are significantly improved if infants are diagnosed and treated within the first few months of life. Read More

    Lentivirus-mediated RNA interference inhibits the tumorigenicity of cluster of differentiation 44(+) tumor cells in hypopharyngeal cancer.
    Oncol Lett 2017 Nov 28;14(5):5354-5360. Epub 2017 Aug 28.
    Department of Otolaryngology and Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
    The present study aimed to investigate whether the inhibition of cluster of differentiation (CD)44 expression reduces the tumorigenicity of CD44(+) cancer stem cells in hypopharyngeal cancer. To assess this, effective recombinant CD44 short hairpin RNA-expressing lentiviruses were produced. Lentivirus-mediated RNA interference (RNAi) was then used to knockdown CD44 gene expression in the hypopharyngeal cancer FaDu cell line. Read More

    Effects of Klf4 and c-Myc Knockdown on Pluripotency Maintenance in Porcine Induced Pluripotent Stem Cell.
    Cell J 2018 Jan 7;19(4):640-646. Epub 2017 Nov 7.
    Division of Physiology, Livestock Research Institute, Council of Agriculture, Executive Yuan, Tainan, Taiwan. Electronic address:
    Objectives: The importance of Oct4 and Sox2 in maintaining pluripotency and self-renewal is well-understood, but the functions of Klf4 and c-Myc has not been fully investigated. In the present study, we attempted to determine the roles of Klf4 and c-Myc on pluripotency maintenance of porcine induced pluripotent stem (piPS) cells.

    Materials And Methods: In this experimental study, we performed short hairpin RNA (shRNA) to knock down the Klf4 and c-Myc functions of piPS cells and examined pluripotency markers and teratoma formation to evaluate piPS cell pluripotency. Read More

    Prostaglandin E2 Increases Lentiviral Vector Transduction Efficiency of Adult Human Hematopoietic Stem and Progenitor Cells.
    Mol Ther 2017 Oct 5. Epub 2017 Oct 5.
    bluebird bio, Inc., 60 Binney Street, Cambridge, MA 02142, USA.
    Gene therapy currently in development for hemoglobinopathies utilizes ex vivo lentiviral transduction of CD34(+) hematopoietic stem and progenitor cells (HSPCs). A small-molecule screen identified prostaglandin E2 (PGE2) as a positive mediator of lentiviral transduction of CD34(+) cells. Supplementation with PGE2 increased lentiviral vector (LVV) transduction of CD34(+) cells approximately 2-fold compared to control transduction methods with no effect on cell viability. Read More

    Medical Devices; Immunology and Microbiology Devices; Classification of the Newborn Screening Test for Severe Combined Immunodeficiency Disorder. Final order.
    • Authors:
    Fed Regist 2017 Oct;82(208):50077-80
    The Food and Drug Administration (FDA or we) is classifying the newborn screening test for severe combined immunodeficiency disorder (SCID) into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the newborn screening test for SCID's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. Read More

    Case Report: Whole exome sequencing identifies variation c.2308G>A p.E770K in RAG1 associated with B- T- NK+ severe combined immunodeficiency.
    F1000Res 2016 18;5:2532. Epub 2016 Oct 18.
    Academy of Scientific and Innovative Research (AcSIR), CSIR-IGIB, Delhi, India.
    Severe combined immunodeficiency is a large clinically heterogeneous group of disorders caused by a defect in the development of humoral or cellular immune responses. At least 13 genes are known to be involved in the pathophysiology of the disease and the mutation spectrum in SCID has been well documented. Mutations of the recombination-activating genes RAG 1 and RAG 2 are associated with a range of clinical presentations including, severe combined immunodeficiency and autoimmunity. Read More

    A Novel Orally Available Small Molecule That Inhibits Hepatitis B Virus Expression.
    J Hepatol 2017 Oct 24. Epub 2017 Oct 24.
    Roche Pharma Research and Early Development, Roche Innovation Center Basel, 4070 Basel, Switzerland. Electronic address:
    Background & Aims: The hallmarks of chronic HBV infection are a high viral load (HBV DNA) and even higher levels (>100-fold in excess of virions) of non-infectious membranous particles containing the tolerogenic viral S antigen (HBsAg). Currently, standard treatment effectively reduces viremia but only rarely results in a functional cure (defined as sustained HBsAg loss). There is an urgent need to identify novel therapies that reduce HBsAg levels and restore virus-specific immune responsiveness in patients. Read More

    Arctigenin inhibits prostate tumor cell growth in vitro and in vivo.
    Clin Nutr Exp 2017 Jun 8;13:1-11. Epub 2017 Apr 8.
    Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA 90059.
    The low bioavailability of most phytochemicals limits their translation to humans. We investigated whether arctigenin, a novel anti-inflammatory lignan from the seeds of Arctium lappa, has favorable bioavailability/potency against prostate cancer. The anticarcinogenic activity of arctigenin was investigated both in vitro using the androgen-sensitive LNCaP and LAPC-4 human prostate cancer cells and pre-malignant WPE1-NA22 cells, and in vivo using xenograft mouse models. Read More

    Frequency of Mycobacterium bovis and mycobacteria in primary immunodeficiencies.
    Turk Pediatri Ars 2017 Sep 1;52(3):138-144. Epub 2017 Sep 1.
    Department of Pediatrics, Pediatric Allergy and Immunology, Ege University Faculty of Medicine, Izmir, Turkey.
    Aim: Susceptibility to mycobacterial diseases is observed in some primary immunodeficiency diseases. In this study, we aimed to evaluate mycobacterial infections in primary immunodeficiency diseases.

    Material And Methods: Patients under follow-up by Ege University Pediatric Immunology Department for severe combined and combined immunodeficiencies, interleukin 12/ interferon gamma receptor deficiency, nuclear factor kappa-beta essential modulator deficiency and chronic granulomatosis disease were evaluated retrospectively in terms of the frequency and characteristics of mycobacterial infections using a questionnaire form for demographic properties, clinical features and laboratory tests. Read More

    Inhibition of miR-142-5P ameliorates disease in mouse models of experimental colitis.
    PLoS One 2017 23;12(10):e0185097. Epub 2017 Oct 23.
    Tytgat Institute for Liver and Intestinal Research, Academic Medical Center (AMC), Amsterdam, the Netherlands.
    Background: MicroRNAs (miRNAs) are epigenetically involved in regulating gene expression. They may be of importance in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to determine the role of miRNAs by their specific blocking in the CD4+CB45RBhi T-cell transfer model of chronic experimental colitis. Read More

    DOCK8 Deficiency Presenting as an IPEX-Like Disorder.
    J Clin Immunol 2017 Nov 23;37(8):811-819. Epub 2017 Oct 23.
    Division of Immunology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Karp Family Building, Room 10-214. 1 Blackfan Street, Boston, MA, 02115, USA.
    Purpose: The dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive-combined immunodeficiency whose clinical spectra include recurrent infections, autoimmunity, malignancies, elevated serum IgE, eczema, and food allergies. Here, we report on patients with loss of function DOCK8 mutations with profound immune dysregulation suggestive of an immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)-like disorder.

    Methods: Immunophenotyping of lymphocyte subpopulations and analysis of DOCK8 protein expression were evaluated by flow cytometry. Read More

    Dynamics of lentiviral infection in vivo in the absence of adaptive immune responses.
    Virology 2017 Oct 19;513:108-113. Epub 2017 Oct 19.
    Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA.
    Understanding the dynamics of acute viral infection is crucial for developing strategies to prevent and control infection. In this study, lentiviral dynamics in a host without adaptive immunity were examined in order to determine kinetic parameters of infection and quantify the effect of neutralizing antibodies in preventing infection, using mathematical modeling of data from equine infectious anemia virus (EIAV) infection of horses with severe combined immunodeficiency (SCID). Estimated parameters were used to calculate the basic reproductive number and virus doubling time and found that the rate that antibodies neutralized virus was ~18 times greater than the virus clearance rate. Read More

    Combined Intravitreal and Systemic Antibiotic Therapy in a Patient with Syphilitic Uveitis.
    Ocul Immunol Inflamm 2017 Oct 20:1-3. Epub 2017 Oct 20.
    b Department of Ophthalmology , Emory University School of Medicine, Emory Eye Center , Atlanta , Georgia , USA.
    Purpose: To report the novel use of combined intravitreal and systemic antibiotic therapy in a patient with syphilitic panuveitis and discuss the management of ocular syphilis.

    Methods: Case report Results: A 45-year old heterosexual male with human immunodeficiency virus (HIV) presented with 1 month of blurry vision in both eyes. Clinical examination revealed a bilateral panuveitis. Read More

    Chronic active Epstein-Barr virus infection as the initial symptom in a Janus kinase 3 deficiency child: Case report and literature review.
    Medicine (Baltimore) 2017 Oct;96(42):e7989
    Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
    Rationale: With the progress of sequencing technology, an increasing number of atypical primary immunodeficiency (PID) patients have been discovered, including Janus kinase 3 (JAK3) gene deficiency.

    Patient Concerns: We report a patient who presented with chronic active Epstein-Barr virus (CAEBV) infection but responded poorly to treatment with ganciclovir.

    Diagnoses: Next-generation sequencing (NGS) was performed, including all known PID genes, after which Sanger sequencing was performed to verify the results. Read More

    The Common Cytokine Receptor γ Chain Family of Cytokines.
    Cold Spring Harb Perspect Biol 2017 Oct 16. Epub 2017 Oct 16.
    Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1674.
    Interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21 form a family of cytokines based on their sharing the common cytokine receptor γ chain (γc), which was originally discovered as the third receptor component of the IL-2 receptor, IL-2Rγ. The IL2RG gene is located on the X chromosome and is mutated in humans with X-linked severe combined immunodeficiency (XSCID). The breadth of the defects in XSCID could not be explained solely by defects in IL-2 signaling, and it is now clear that γc is a shared receptor component of the six cytokines noted above, making XSCID a disease of defective cytokine signaling. Read More

    Immune Reconstitution and Survival of 100 SCID Patients Post Hematopoietic Cell Transplant: A PIDTC Natural History Study.
    Blood 2017 Oct 11. Epub 2017 Oct 11.
    University of California, San Francisco, United States.
    The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010-2014, including 68 with typical SCID and 32 with leaky SCID, Omenn Syndrome or Reticular Dysgenesis. Most (59%) were diagnosed by newborn screening or family history. Read More

    Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1.
    Sci Transl Med 2017 Oct;9(411)
    San Raffaele Telethon Institute for Gene Therapy, 20132 Milan, Italy.
    Targeted genome editing in hematopoietic stem/progenitor cells (HSPCs) is an attractive strategy for treating immunohematological diseases. However, the limited efficiency of homology-directed editing in primitive HSPCs constrains the yield of corrected cells and might affect the feasibility and safety of clinical translation. These concerns need to be addressed in stringent preclinical models and overcome by developing more efficient editing methods. Read More

    A metabolomics and lipidomics study of mouse models of type 1 diabetes highlights divergent metabolism in purine and tryptophan metabolism prior to disease on-set.
    J Proteome Res 2017 Oct 10. Epub 2017 Oct 10.
    With the increase in incidence of type 1 diabetes (T1DM), particularly in Westernised societies, there is an urgent need to understand the early molecular and metabolic alterations that accompany the autoimmune disease. This is not least because in murine models early intervention can prevent the development of overt disease. In this study we have applied a liquid chromatography (LC-) and gas chromatography (GC-) mass spectrometry (MS) metabolomics and lipidomics analysis of blood plasma and pancreas tissue extracts to follow the progression of disease in three models related to autoimmune diabetes: the non-obese diabetic (NOD) mouse, which is susceptible to the development of autoimmune diabetes, and the NOD-E (transgenic NOD mice that express the I-E heterodimer of the major histocompatibility complex II) and NOD- severe combined immunodeficiency (SCID) mouse strains, two models protected from the development of diabetes. Read More

    Late presenting atypical severe combined immunodeficiency (SCID) associated with a novel missense mutation in DCLRE1C.
    Pediatr Allergy Immunol 2017 Oct 5. Epub 2017 Oct 5.
    Department of Clinical Immunology, Karolinska University Hospital, and Karolinska Institutet, Stockholm, Sweden.
    Immunodeficiency associated with mutations in the DNA cross-link repair 1C gene (DCLRE1C) can have variable clinical presentations including severe combined immunodeficiency (SCID), Omenn syndrome, atypical SCID or common variable immunodeficiency (CVID) (1-3). DCLRE1C encodes the protein Artemis, a nuclease with intrinsic 5'-3' exonuclease activity on single-stranded DNA that is involved in non-homologous end joining (NHEJ). Artemis is essential for V(D)J recombination of the immunoglobulin and T-cell receptor genes that occur during B- and T-cell development. Read More

    Inflammatory Bowel Disease in Chronic Granulomatous Disease: an emerging problem over a twenty years' experience.
    Pediatr Allergy Immunol 2017 Oct 5. Epub 2017 Oct 5.
    University Department of Pediatrics, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital IRCCS and University of Rome Tor Vergata, Rome, Italy.
    Background: Chronic Granulomatous Disease (CGD) is a primary immunodeficiency of phagocytes, characterized by life-threatening infections and hyperinflammation. Due to survival improvement, Inflammatory Bowel Disease (IBD) is becoming increasingly relevant. Here we report our 20-year experience. Read More

    Rev Paul Pediatr 2017 Jan-Mar;35(1):25-32
    Departamento de Imunologia, Universidade de São Paulo (USP), São Paulo, SP, Brasil.
    Objective: To validate the quantification of T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) by real-time polymerase chain reaction (qRT-PCR) for newborn screening of primary immunodeficiencies with defects in T and/or B cells in Brazil.

    Methods: Blood samples from newborns and controls were collected on filter paper. DNA was extracted and TRECs, and KRECs were quantified by a duplex real-time PCR. Read More

    Non-random length distribution of individual telomeres in immunodeficiency, centromeric instability and facial anomalies syndrome, type I.
    Hum Mol Genet 2017 Nov;26(21):4244-4256
    Molecular Medicine Laboratory, Rambam Health Care Campus and Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel.
    Mutations in the de novo DNA methyltransferase DNMT3B lead to Immunodeficiency, Centromeric Instability and Facial anomalies (ICF) syndrome, type I. This syndrome is characterized, among other hypomethylated genomic loci, by severe subtelomeric hypomethylation that is associated with abnormally short telomere length. While it was demonstrated that the mean telomere length is significantly shorter in ICF type I cells, it is unknown whether all telomeres are equally vulnerable to shortening. Read More

    Approaches to the removal of T-lymphocytes to minimize graft-versus-host disease in patients with primary immunodeficiencies who do not have a matched sibling donor.
    Curr Opin Allergy Clin Immunol 2017 Dec;17(6):414-420
    aInstitute of Cellular Medicine, Newcastle University, Medical School, Framlington Place bPaediatric Immunology and HSCT, Great North Children's Hospital, Queen Victoria Road, Newcastle Upon Tyne, UK.
    Purpose Of Review: Since the advent of T-lymphocyte depletion in hematopoietic stem cell transplantation (HSCT) for primary immunodeficiency, survival following this procedure has remained poor compared to results when using matched sibling or matched unrelated donors, over the last 40 years. However, three new techniques are radically altering the approach to HSCT for those with no matched donor, particularly those with primary immunodeficiencies which are not severe combined immunodeficiency.

    Recent Findings: Three main techniques of T-lymphocyte depletion are altering donor choice for patients with primary immunodeficiencies and have improved transplant survival for primary immunodeficiencies to over 90%, equivalent to that for matched sibling and matched unrelated donor transplants. Read More

    Targeted genome editing restores T cell differentiation in a humanized X-SCID pluripotent stem cell disease model.
    Sci Rep 2017 Sep 29;7(1):12475. Epub 2017 Sep 29.
    Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, Freiburg, Germany.
    The generation of T cells from pluripotent stem cells (PSCs) is attractive for investigating T cell development and validating genome editing strategies in vitro. X-linked severe combined immunodeficiency (X-SCID) is an immune disorder caused by mutations in the IL2RG gene and characterised by the absence of T and NK cells in patients. IL2RG encodes the common gamma chain, which is part of several interleukin receptors, including IL-2 and IL-7 receptors. Read More

    From clinical observations and molecular dissection to novel therapeutic strategies for primary immunodeficiency disorders.
    Am J Med Genet A 2017 Sep 21. Epub 2017 Sep 21.
    Department of Pediatrics and Seattle Children's Research Institute, University of Washington, Seattle, Washington.
    The field of primary immunodeficiency diseases (PID) is rapidly expanding with more than 300 genetically defined disorders that have been clinically described and molecularly analyzed. The molecular dissection of these entities has led to the discovery of new immunologic pathways and to novel and effective disease-specific therapies. This review provides a summary of these primary immune defects categorized by clinical phenotype and molecular similarity as defined by the International Union of Immunologic Societies (IUIS) Expert Committee for PID. Read More

    Hepatic Legionella pneumophila Infection in an Infant with Severe Combined Immunodeficiency.
    Pediatr Infect Dis J 2017 Sep 20. Epub 2017 Sep 20.
    1Pediatric Infectious Diseases, Boston Medical Center 2Precision Vaccines Program 3Division of Infectious Diseases, Boston Children's Hospital 4Harvard Medical School; Boston, USA 5Division of Pathology, Boston Children's Hospital.
    Rare cases of extrapulmonary involvement in Legionella spp. infections have been described, mostly in immunocompromised adults. We report a case of a 2 month old male with reticular dysgenesis variant of severe combined immune deficiency (SCID) with multiple liver lesions. Read More

    Analysis of Hepatitis C Virus Particle Heterogeneity in Immunodeficient Human Liver Chimeric fah-/- Mice.
    Cell Mol Gastroenterol Hepatol 2017 Nov 19;4(3):405-417. Epub 2017 Jul 19.
    Center for the Study of Hepatitis C, The Rockefeller University, New York, New York.
    Background & Aims: Hepatitis C virus (HCV) is a leading cause of chronic liver diseases and the most common indication for liver transplantation in the United States. HCV particles in the blood of infected patients are characterized by heterogeneous buoyant densities, likely owing to HCV association with lipoproteins. However, clinical isolates are not infectious in vitro and the relative infectivity of the particles with respect to their buoyant density therefore cannot be determined, pointing to the need for better in vivo model systems. Read More

    Novel blood test to predict neoplastic activity in healthy patients and metastatic recurrence after primary tumor resection.
    J Circ Biomark 2016 Jan-Dec;5:1849454416663661. Epub 2016 Nov 4.
    Cancer Research Program, McGill University Health Centre-Research Institute, Montreal, Quebec, Canada.
    We reported that single oncosuppressor-mutated (SOM) cells turn malignant when exposed to cancer patients' sera. We tested the possibility to incorporate this discovery into a biological platform able to detect cancer in healthy individuals and to predict metastases after tumor resection. Blood was drawn prior to tumor resection and within a year after surgery. Read More

    FOXN1 Deficiency: from the Discovery to Novel Therapeutic Approaches.
    J Clin Immunol 2017 Nov 21;37(8):751-758. Epub 2017 Sep 21.
    Department of Translational Medical Sciences, Section of Pediatrics, Federico II University, Via S. Pansini, 5, 80131, Naples, Italy.
    Since the discovery of FOXN1 deficiency, the human counterpart of the nude mouse, a growing body of evidence investigating the role of FOXN1 in thymus and skin, has been published. FOXN1 has emerged as fundamental for thymus development, function, and homeostasis, representing the master regulator of thymic epithelial and T cell development. In the skin, it also plays a pivotal role in keratinocytes and hair follicle cell differentiation, although the underlying molecular mechanisms still remain to be fully elucidated. Read More

    Poliovirus Excretion in Children with Primary Immunodeficiency Disorders, India.
    Emerg Infect Dis 2017 10;23(10):1664-1670
    Prolonged excretion of poliovirus can occur in immunodeficient patients who receive oral polio vaccine, which may lead to propagation of highly divergent vaccine-derived polioviruses (VDPVs), posing a concern for global polio eradication. This study aimed to estimate the proportion of primary immunodeficient children with enterovirus infection and to identify the long-term polio/nonpolio enterovirus excreters in a tertiary care unit in Mumbai, India. During September 2014-April 2017, 151 patients received diagnoses of primary immunodeficiency (PID). Read More

    Differential modulation of IL-12 family cytokines in autoimmune islet graft failure in mice.
    Diabetologia 2017 Dec 19;60(12):2409-2417. Epub 2017 Sep 19.
    Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, 161, Section 6, MinChuan East Road, Neihu, Taipei 114, Taiwan.
    Aims/hypothesis: The relative contribution of T helper (Th)1 and Th17 cells in graft rejection is inconclusive, on the basis of evidence provided by different T cell-related cytokine-deficient animal models and graft types.

    Methods: We used novel antigen-presenting-cell-specific Il-12p35 (also known as Il12a)-knockout (KO), IL-23p19-knockdown (KD) and IL-27p28-KD strategies to investigate T cell differentiation in islet graft rejection.

    Results: In vitro dendritic cell-T cell coculture experiments revealed that dendritic cells from Il-12p35-KO and IL-23p19-KD mice showed reduced ability to stimulate IFN-γ and IL-17 production in T cells, respectively. Read More

    Characteristics of primary side population cervical cancer cells.
    Oncol Lett 2017 Sep 18;14(3):3536-3544. Epub 2017 Jul 18.
    Department of Gynecological Oncology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
    The aim of the present study was to identify and characterize side population (SP) cells in primary cervical cancer. A primary culture was successfully established, and the SP cells were isolated via fluorescence-activated cell sorting. Subsequently, in vitro analysis of clonogenic capacity by soft agar assay and in vivo analysis of tumorigenicity were performed. Read More

    Isolation and characterization of adult mammary stem cells from breast cancer-adjacent tissues.
    Oncol Lett 2017 Sep 28;14(3):2894-2902. Epub 2017 Jun 28.
    Department of Breast Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
    Normal adult mammary stem cells (AMSCs) are promising sources for breast reconstruction, particularly following the resection of breast tumors. However, carcinogenic events can potentially convert normal AMSCs to cancer stem cells, posing a safety concern for the use of AMSCs for clinical tissue regeneration. In the present study, AMSCs and autologous primary breast cancer cells were isolated and compared for their ability to differentiate, their gene expression profile, and their potential to form tumors in vivo. Read More

    Reversing HIV latency via sphingosine-1-phosphate receptor 1 signaling.
    AIDS 2017 Nov;31(18):2443-2454
    aInstitut de Génétique Humaine, CNRS-Université de Montpellier UMR9002 bARPEGE Pharmacology Screening Interactome platform facility, Institut de Génomique Fonctionnelle, Montpellier cLaboratoire coopératif SPLICOS SAS, IGMM-CNRS-UMR5535, Montpellier dInstitut de Génomique Fonctionnelle, CNRS-UMR5203, INSERM-U661, Université de Montpellier eInstitut de Génétique Moléculaire de Montpellier, CNRS-UMR 5535, Université de Montpellier fUniversité de Montpellier, Montpellier gCentre Hospitalier Universitaire Carémeau, UF d'Immunologie, Nîmes, France.
    Objective: In this study, we looked for a new family of latency reversing agents.

    Design: We searched for G-protein-coupled receptors (GPCR) coexpressed with the C-C chemokine receptor type 5 (CCR5) in primary CD4 T cells that activate infected cells and boost HIV production.

    Methods: GPCR coexpression was unveiled by reverse transcriptase-PCR. Read More

    Epigenetic Silencing of miRNA-34a in Human Cholangiocarcinoma via EZH2 and DNA Methylation: Impact on Regulation of Notch Pathway.
    Am J Pathol 2017 Oct;187(10):2288-2299
    Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, Louisiana. Electronic address:
    Aberrant expression and regulation of miRNAs have been implicated in multiple stages of tumorigenic processes. The current study was designed to explore the biological function and epigenetic regulation of miR-34a in human cholangiocarcinoma (CCA). Our data show that the expression of miR-34a is decreased significantly in CCA cells compared with non-neoplastic biliary epithelial cells. Read More

    Long term outcomes of severe combined immunodeficiency: therapy implications.
    Expert Rev Clin Immunol 2017 Nov 23;13(11):1029-1040. Epub 2017 Sep 23.
    b Allergy Immunology and Blood and Marrow Transplant Division , University of California San Francisco, Benioff Children's Hospital , San Francisco , CA , USA.
    Introduction: Newborn screening has led to a better understanding of the prevalence of Severe Combined Immunodeficiency (SCID) overall and in terms of specific genotypes. Survival has improved following hematopoietic stem cell transplantation (HCT) with the best outcomes seen following use of a matched sibling donor. However, questions remain regarding the optimal alternative donor source, appropriate use of conditioning and the impact of these decisions on immune reconstitution and other late morbidities. Read More

    A novel mutation in the JH4 domain of JAK3 causing severe combined immunodeficiency complicated by vertebral osteomyelitis.
    Clin Immunol 2017 Oct 14;183:198-200. Epub 2017 Sep 14.
    Department of Allergy and immunology, Boston Children's Hospital, United States.
    JAK3 is a tyrosine kinase essential for signaling downstream of the common gamma chain subunit shared by multiple cytokine receptors. JAK3 deficiency results in T(-)B(+)NK(-) severe combined immune deficiency (SCID). We report a patient with SCID due to a novel mutation in the JAK3 JH4 domain. Read More

    Gene Therapy Approaches to Immunodeficiency.
    Hematol Oncol Clin North Am 2017 Oct 29;31(5):823-834. Epub 2017 Jun 29.
    Infection, Immunity, Inflammation, Molecular and Cellular Immunology Section, University College London, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK. Electronic address:
    Transfer of gene-corrected autologous hematopoietic stem cells in patients with primary immunodeficiencies has emerged as a new therapeutic approach. Patients with various conditions lacking a suitable donor have been treated with retroviral vectors and a gene-addition strategy. Initial promising results were shadowed by the occurrence of malignancies in some of these patients. Read More

    Opening Marrow Niches in Patients Undergoing Autologous Hematopoietic Stem Cell Gene Therapy.
    Hematol Oncol Clin North Am 2017 Oct 28;31(5):809-822. Epub 2017 Jul 28.
    Department of Clinical Pharmacy, University of California San Francisco, 600 16th Street, Room N474F, San Francisco, CA 94158-0622, USA.
    Successful gene therapy for genetic disorders requires marrow niches to be opened to varying degrees to engraft gene-corrected hematopoietic stem cells (HSC). For example, in severe combined immunodeficiency, relatively limited chimerism is necessary for both T- and B-cell immune reconstitution, whereas for inborn errors of metabolism maximal donor chimerism is the goal. Currently, alkylating chemotherapy is used for this purpose. Read More

    The development of T cells from stem cells in mice and humans.
    Future Sci OA 2017 Aug 16;3(3):FSO186. Epub 2017 Mar 16.
    Department of Immunohematology & Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
    T cells develop from hematopoietic stem cells in the specialized microenvironment of the thymus. The main transcriptional players of T-cell differentiation such as Notch, Tcf-1, Gata3 and Bcl11b have been identified, but their role and regulation are not yet completely understood. In humans, functional experiments on T-cell development have traditionally been rather difficult to perform, but novel in vitro culture systems and in vivo xenograft models have allowed detailed studies on human T-cell development. Read More

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