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    7630 results match your criteria Severe Combined Immunodeficiency

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    A novel PGM3 mutation is associated with a severe phenotype of bone marrow failure, severe combined immunodeficiency, skeletal dysplasia, and congenital malformations.
    J Bone Miner Res 2017 May 22. Epub 2017 May 22.
    Centre Hospitalier Universitaire Sainte-Justine, Pediatrics Montreal, QC, Canada.
    Congenital disorders of glycosylation (CDGs) affect multiple systems and present a broad spectrum of clinical features, often including skeletal dysplasia and exome sequencing has led to the identification of new CDG genes . Immune and skeletal phenotypes associated with mutations in PGM3, encoding a protein which converts N-acetyl-glucosamine-6-phosphate into N-acetyl-glucosamine-1-phosphate, were recently reported. Through exome sequencing, we identified a novel homozygous mutation (c. Read More

    Development of real-time RT-PCR assays for detection of three classes of HHV-6A gene transcripts.
    J Med Virol 2017 May 23. Epub 2017 May 23.
    Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
    Human herpesvirus 6 (HHV-6), a member of the betaherpesvirus family, has two distinct species: HHV-6A and HHV-6B. HHV-6B real-time reverse transcription polymerase chain reaction (RT-PCR) has been used to distinguish between active and latent viral infection. In this study, we developed a real-time RT-PCR assay to detect HHV-6A-specific transcripts and evaluated its reliability for analysis of clinical samples. Read More

    Identification of 22q11.2 Deletion Syndrome via Newborn Screening for Severe Combined Immunodeficiency.
    J Clin Immunol 2017 May 24. Epub 2017 May 24.
    The 22q and You Center, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
    Purpose: Chromosome 22q11.2 deletion syndrome (22q11.2DS), the most common cause of DiGeorge syndrome, is quite variable. Read More

    Haematopoietic stem cell transplantation for severe combined immunodeficiency: Long-term health outcomes and patient perspectives.
    J Paediatr Child Health 2017 May 17. Epub 2017 May 17.
    Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Sydney, New South Wales, Australia.
    Aim: To examine the long-term follow-up and health outcomes of patients who have undergone haematopoietic stem cell transplant (HSCT) for severe combined immunodeficiency (SCID).

    Methods: Through a structured questionnaire, we examined follow-up arrangements and long-term health outcomes in 22 children who have had a successful HSCT for SCID during the period of 1984-2012 at the Sydney Children's Hospital, Sydney, Australia.

    Results: Most children considered themselves healthy and 'cured' from SCID. Read More

    Jak3 deficiency blocks innate lymphoid cell development.
    Mucosal Immunol 2017 May 17. Epub 2017 May 17.
    Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
    Loss-of-function mutations in the tyrosine kinase JAK3 cause autosomal recessive severe combined immunodeficiency (SCID). Defects in this form of SCID are restricted to the immune system, which led to the development of immunosuppressive JAK inhibitors. We find that the B6. Read More

    Clinical, Immunological, Molecular Analyses and Outcomes of Iranian Patients with LRBA Deficiency: A Longitudinal Study.
    Pediatr Allergy Immunol 2017 May 17. Epub 2017 May 17.
    Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
    Background: LPS-responsive beige-like anchor protein (LRBA) deficiency is a combined immunodeficiency caused by mutation in LRBA gene. The patients have a variety of clinical symptoms including hypogammaglobulinemia, recurrent infections, autoimmunity and enteropathy.

    Methods: A total of 17 LRBA-deficient patients were enrolled in this longitudinal study. Read More

    Intrathymic injection of hematopoietic progenitor cells establishes functional T cell development in a mouse model of severe combined immunodeficiency.
    J Hematol Oncol 2017 May 16;10(1):109. Epub 2017 May 16.
    Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
    Background: Even though hematopoietic stem cell transplantation can be curative in patients with severe combined immunodeficiency, there is a need for additional strategies boosting T cell immunity in individuals suffering from genetic disorders of lymphoid development. Here we show that image-guided intrathymic injection of hematopoietic stem and progenitor cells in NOD-scid IL2rγ(null) mice is feasible and facilitates the generation of functional T cells conferring protective immunity.

    Methods: Hematopoietic stem and progenitor cells were isolated from the bone marrow of healthy C57BL/6 mice (wild-type, Luciferase(+), CD45. Read More

    Idiopathic collapsing focal segmental glomerulosclerosis in an 81-year-old Japanese woman: a case report and review of the literature.
    CEN Case Rep 2016 Nov 15;5(2):197-202. Epub 2016 Jun 15.
    Department of Nephrology, Yokohama City Minato Red Cross Hospital, 3-12-1 Shinyamashita, Naka-ku, Yokohama, Kanagawa, 231-8682, Japan.
    Focal segmental glomerulosclerosis (FSGS) is classified into five variants, with the collapsing variant being the most rare. Collapsing FSGS is characterized by a black racial predominance and is often associated with human immunodeficiency virus-associated nephropathy. However, the number of idiopathic cases is increasing and the presentation of non-black patients becoming more routine. Read More

    An evaluation of the TREC assay with regard to the integration of SCID screening into the Dutch newborn screening program.
    Clin Immunol 2017 May 6;180:106-110. Epub 2017 May 6.
    Centre for Infectious Diseases Research, Diagnostics and Screening, Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Electronic address:
    Newborn screening of severe combined immunodeficiency through the detection of T-cell receptor excision circles will provide the opportunity of treating before the occurrence of life-threatening infections. With the EnLite Neonatal TREC assay (PerkinElmer) and end-point PCR, 39 samples (3.0%) of 1295 heel prick cards of the Dutch newborn screening program required a retest after initial analysis. Read More

    Oncogenic activity of amplified miniature chromosome maintenance 8 in human malignancies.
    Oncogene 2017 May 8. Epub 2017 May 8.
    Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
    Miniature chromosome maintenance (MCM) proteins play critical roles in DNA replication licensing, initiation and elongation. MCM8, one of the MCM proteins playing a critical role in DNA repairing and recombination, was found to have overexpression and increased DNA copy number in a variety of human malignancies. The gain of MCM8 is associated with aggressive clinical features of several human cancers. Read More

    Genetic Engineering and Manufacturing of Hematopoietic Stem Cells.
    Mol Ther Methods Clin Dev 2017 Jun 18;5:96-105. Epub 2017 Mar 18.
    Cell Therapy and Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
    The marketing approval of genetically engineered hematopoietic stem cells (HSCs) as the first-line therapy for the treatment of severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) is a tribute to the substantial progress that has been made regarding HSC engineering in the past decade. Reproducible manufacturing of high-quality, clinical-grade, genetically engineered HSCs is the foundation for broadening the application of this technology. Herein, the current state-of-the-art manufacturing platforms to genetically engineer HSCs as well as the challenges pertaining to production standardization and product characterization are addressed in the context of primary immunodeficiency diseases (PIDs) and other monogenic disorders. Read More

    Recommendations for Screening and Management of Late Effects in SCID Patients after Allogenic Hematopoietic Cell Transplantation (HCT): A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT.
    Biol Blood Marrow Transplant 2017 May 4. Epub 2017 May 4.
    UCSF Department of Pediatrics, Allergy, Immunology, and Blood and Marrow Transplant Division, San Francisco California, USA.
    Severe Combined Immunodeficiency (SCID) is effectively treated with HCT with overall survival approaching 90% in contemporary reports. However, survivors are at risk for development of late complications due to the variable durability of high quality immune function, underlying genotype of SCID, comorbidities due to infections in the pre- and post- transplant period and use of conditioning pre-transplant. An international group of transplant experts was convened in 2016 to review the current knowledge of late effects seen in SCID patients following HCT, and develop recommendations for screening and monitoring for late effects. Read More

    Hypoxic preconditioning of myoblasts implanted in a tissue engineering chamber significantly increases local angiogenesis via upregulation of myoblast VEGF-A expression, and downregulation of miRNA-1, miRNA-206 and Angiopoietin 1.
    J Tissue Eng Regen Med 2017 May 6. Epub 2017 May 6.
    O'Brien Institute Department, at St Vincent's Institute, Melbourne, Australia.
    Vascularization is a major hurdle for growing 3 dimensional tissue engineered constructs. This study investigated the mechanisms involved in hypoxic preconditioning of primary rat myoblasts in vitro and their influence on local angiogenesis post-implantation. Primary rat myoblast cultures were exposed to 90 minutes hypoxia at < 1% oxygen followed by normoxia for 24 hours. Read More

    Durable Control of Autoimmune Diabetes in Mice Achieved by Intraperitoneal Transplantation of "Neo-Islets," Three-Dimensional Aggregates of Allogeneic Islet and "Mesenchymal Stem Cells".
    Stem Cells Transl Med 2017 May 3. Epub 2017 May 3.
    SymbioCellTech, LLC, Salt Lake City, Utah, USA.
    Novel interventions that reestablish endogenous insulin secretion and thereby halt progressive end-organ damage and prolong survival of patients with autoimmune Type 1 diabetes mellitus (T1DM) are urgently needed. While this is currently accomplished with allogeneic pancreas or islet transplants, their utility is significantly limited by both the scarcity of organ donors and life-long need for often-toxic antirejection drugs. Coadministering islets with bone marrow-derived mesenchymal stem cells (MSCs) that exert robust immune-modulating, anti-inflammatory, anti-apoptotic, and angiogenic actions, improves intrahepatic islet survival and function. Read More

    CD8 T cells contribute to lacrimal gland pathology in the nonobese diabetic mouse model of Sjögren syndrome.
    Immunol Cell Biol 2017 May 3. Epub 2017 May 3.
    Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
    Sjögren syndrome is an autoimmune disease characterized by targeted destruction of the lacrimal and salivary glands resulting in symptoms of severe ocular and oral dryness. Despite its prevalence, the mechanisms driving autoimmune manifestations are unclear. In patients and in the nonobese diabetic (NOD) mouse model of Sjögren syndrome, lymphocytic infiltrates consist of CD4 and CD8 T cells, although the role of CD8 T cells in disease pathogenesis has been largely unexplored. Read More

    Cooperation of neurotrophin receptor TrkB and Her2 in breast cancer cells facilitates brain metastases.
    Breast Cancer Res 2017 Apr 26;19(1):51. Epub 2017 Apr 26.
    Division of Neurosurgery, Beckman Research Institute, City of Hope, 1500 E. Duarte Rd, Duarte, CA, 91010, USA.
    Background: Patients with primary breast cancer that is positive for human epidermal growth factor receptor 2 (Her2+) have a high risk of developing metastases in the brain. Despite gains with systemic control of Her2+ disease using molecular therapies, brain metastases remain recalcitrant to therapeutic discovery. The clinical predilection of Her2+ breast cancer cells to colonize the brain likely relies on paracrine mechanisms. Read More

    Augmented expression of RUNX1 deregulates the global gene expression of U87 glioblastoma multiforme cells and inhibits tumor growth in mice.
    Tumour Biol 2017 Apr;39(4):1010428317698357
    1 The Laboratory of Molecular Genetics, Hepatic-Bili-Pancreatic Cancer Research, Department of Surgery B, Tel Aviv Sourasky Medical Center, The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
    Glioblastoma multiforme is the most common and aggressive primary brain tumor in adults. A mesenchymal phenotype was associated with tumor aggressiveness and poor prognosis in glioblastoma multiforme patients. Recently, the transcription factor RUNX1 was suggested as a driver of the glioblastoma multiforme mesenchymal gene expression signature; however, its independent role in this process is yet to be described. Read More

    Impact of altered endogenous IgG on unspecific mAb clearance.
    J Pharmacokinet Pharmacodyn 2017 Apr 24. Epub 2017 Apr 24.
    Institute of Mathematics, Universität Potsdam, Karl-Liebknecht-Str. 24-25, 14476, Potsdam, Golm, Germany.
    Immunodeficient mice are crucial models to evaluate the efficacy of monoclonal antibodies (mAbs). When studying mAb pharmacokinetics (PK), protection from elimination by binding to the neonatal Fc receptor (FcRn) is known to be a major process influencing the unspecific clearance of endogenous and therapeutic IgG. The concentration of endogenous IgG in immunodeficient mice, however is reduced, and this effect on the FcRn protection mechanism and subsequently on unspecific mAb clearance is unknown, yet of great importance for the interpretation of mAb PK data. Read More

    Linking newborn severe combined immunodeficiency screening with targeted exome sequencing: A case report.
    J Allergy Clin Immunol Pract 2017 Apr 21. Epub 2017 Apr 21.
    Immunology, Allergy and Rheumatology Section, Baylor College of Medicine, Houston, Texas; Department of Pediatrics, Texas Children's Hospital, Houston, Texas; Baylor College of Medicine, Houston, Texas.

    Cuprous oxide nanoparticle-inhibited melanoma progress by targeting melanoma stem cells.
    Int J Nanomedicine 2017 5;12:2553-2567. Epub 2017 Apr 5.
    Department of Cell Biology, Second Military Medical University.
    Recent studies have shown that metal and metal oxide have a potential function in antitumor therapy. Our previous studies demonstrated that cuprous oxide nanoparticles (CONPs) not only selectively induce apoptosis of tumor cells in vitro but also inhibit the growth and metastasis of melanoma by targeting mitochondria with little hepatic and renal toxicities in mice. As a further study, our current research revealed that CONPs induced apoptosis of human melanoma stem cells (CD271(+/high) cells) in A375 and WM266-4 melanoma cell lines and could significantly suppress the expression of MITF, SOX10 and CD271 involved in the stemness maintenance and tumorigenesis of melanoma stem cells. Read More

    Digoxin Attenuates Murine Experimental Colitis by Downregulating Th17-related Cytokines.
    Inflamm Bowel Dis 2017 May;23(5):728-738
    *First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; Departments of †Health Science, ‡Infectious Diseases, §Regenerative and infectious Pathology, and ‖Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan; and ¶Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.
    Background: Digoxin, a cardiac glycoside used for the treatment of heart failure, was reported to inhibit the retinoid-related orphan receptor gamma t (RORγt) and attenuate the severity of experimental autoimmune encephalomyelitis and arthritis in mice. However, the effects of digoxin in a mice model of inflammatory bowel disease have not been elucidated.

    Methods: Colitis was induced in severe combined immunodeficiency mice by adoptive transfer of CD45RB CD4 T cells. Read More

    Ecto-5'-nucleotidase (CD73) is a biomarker for clear cell renal carcinoma stem-like cells.
    Oncotarget 2017 May;8(19):31977-31992
    School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou 215123, China.
    Identification of a specific biomarker for cancer stem cells (CSCs) is of potential applications in the development of effective therapeutic strategies for renal cell carcinoma (RCC). In this study, both the RCC cell line 786-O and surgically removed clear cell RCC (ccRCC) tissues were implemented to grew as spheroids in serum-free medium supplemented with mitogens. This subpopulation possessed key characteristics defining CSCs. Read More

    Haematopoietic stem cell transplantation in primary immunodeficiency patients in the Black Sea Region of Turkey.
    Turk J Haematol 2017 Apr 13. Epub 2017 Apr 13.
    Objective: Haematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders.

    Materials And Methods: We retrospectively reviewed paediatric cases that were diagnosed with primary immunodeficiencies and scheduled for haematopoietic stem cell transplantation.

    Results: We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received haematopoietic stem cell transplantation. Read More

    Distribution of FcRn Across Species and Tissues.
    J Histochem Cytochem 2017 Apr 1:22155417705095. Epub 2017 Apr 1.
    Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland (SL, BJ, MBO, AH, SK).
    The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I type molecule that binds to, transports, and recycles immunoglobulin G (IgG) and albumin, thereby protecting them from lysosomal degradation. Therefore, besides the knowledge of FcRn affinity, FcRn protein expression is critical in understanding the pharmacokinetic behavior of Fc-containing biotherapeutics such as monoclonal antibodies. The goal of this investigation was to achieve for the first time a comparative assessment of FcRn distribution across a variety of tissues and species. Read More

    Evolving Gene Therapy in Primary Immunodeficiency.
    Mol Ther 2017 May 31;25(5):1132-1141. Epub 2017 Mar 31.
    Boston Children's Hospital and Dana-Farber Cancer Institute, Harvard Medical School and Harvard Stem Cell Institute, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address:
    Prior to the first successful bone marrow transplant in 1968, patients born with severe combined immunodeficiency (SCID) invariably died. Today, with a widening availability of newborn screening, major improvements in the application of allogeneic procedures, and the emergence of successful hematopoietic stem and progenitor cell (HSC/P) gene therapy, the majority of these children can be identified and cured. Here, we trace key steps in the development of clinical gene therapy for SCID and other primary immunodeficiencies (PIDs), and review the prospects for adoption of new targets and technologies. Read More

    Use of p53-Silenced Endothelial Progenitor Cells to Treat Ischemia in Diabetic Peripheral Vascular Disease.
    J Am Heart Assoc 2017 Apr 1;6(4). Epub 2017 Apr 1.
    Department of Medicine, The George Washington University, Washington, DC
    Background: Peripheral vascular disease is a major diabetes mellitus-related complication. In this study, we noted that expressions of proapoptotic p53 gene and its downstream cascade gene such as p21 are upregulated in hyperglycemia. Therefore, we investigated whether p53- and p21-silenced endothelial progenitor cells (EPCs) were able to survive in hyperglycemic milieu, and whether transplantation of either p53 knockout (KO) or p21KO or p53- and p21-silenced EPCs could improve collateral vessel formation and blood flow in diabetic vaso-occlusive peripheral vascular disease mouse models. Read More

    Pathology of Aging in NOD scid gamma Female Mice.
    Vet Pathol 2017 Jan 1:300985817698210. Epub 2017 Jan 1.
    1 Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, The Rockefeller University, Weill Cornell Medicine, New York, NY, USA.
    In the past decade, NOD.Cg- Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NSG, NOD scid gamma) mice have become a model of choice in several areas of biomedical research; however, comprehensive data on their spontaneous age-related pathology are not currently available in the literature. The prevalence of spontaneous morbidity affecting aged NSG female breeders enrolled in a parasitology study was documented with classification of neoplastic and non-neoplastic (inflammatory, metabolic, degenerative) lesions. Read More

    Cytoreductive conditioning intensity predicts clonal diversity in ADA-SCID retroviral gene therapy patients.
    Blood 2017 May 28;129(19):2624-2635. Epub 2017 Mar 28.
    Department of Microbiology, Immunology and Molecular Genetics and.
    Retroviral gene therapy has proved efficacious for multiple genetic diseases of the hematopoietic system, but roughly half of clinical gene therapy trial protocols using gammaretroviral vectors have reported leukemias in some of the patients treated. In dramatic contrast, 39 adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) patients have been treated with 4 distinct gammaretroviral vectors without oncogenic consequence. We investigated clonal dynamics and diversity in a cohort of 15 ADA-SCID children treated with gammaretroviral vectors and found clear evidence of genotoxicity, indicated by numerous common integration sites near proto-oncogenes and by increased abundance of clones with integrations near MECOM and LMO2 These clones showed stable behavior over multiple years and never expanded to the point of dominance or dysplasia. Read More

    Oncolytic Adenoviruses Armed with Tumor Necrosis Factor Alpha and Interleukin-2 Enable Successful Adoptive Cell Therapy.
    Mol Ther Oncolytics 2017 Mar 31;4:77-86. Epub 2016 Dec 31.
    Cancer Gene Therapy Group, Faculty of Medicine, University of Helsinki, 00290 Helsinki, Finland; TILT Biotherapeutics, Ltd., 00290 Helsinki, Finland; Comprehensive Cancer Center, Helsinki University Hospital, 00290 Helsinki, Finland.
    Adoptive cell therapy holds much promise in the treatment of cancer but results in solid tumors have been modest. The notable exception is tumor-infiltrating lymphocyte (TIL) therapy of melanoma, but this approach only works with high-dose preconditioning chemotherapy and systemic interleukin (IL)-2 postconditioning, both of which are associated with toxicities. To improve and broaden the applicability of adoptive cell transfer, we constructed oncolytic adenoviruses coding for human IL-2 (hIL2), tumor necrosis factor alpha (TNF-α), or both. Read More

    INSPIIRED: Quantification and Visualization Tools for Analyzing Integration Site Distributions.
    Mol Ther Methods Clin Dev 2017 Mar 18;4:17-26. Epub 2016 Dec 18.
    Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6076, USA.
    Analysis of sites of newly integrated DNA in cellular genomes is important to several fields, but methods for analyzing and visualizing these datasets are still under development. Here, we describe tools for data analysis and visualization that take as input integration site data from our INSPIIRED pipeline. Paired-end sequencing allows inference of the numbers of transduced cells as well as the distributions of integration sites in target genomes. Read More

    Tanshinone IIA increases protein expression levels of PERK, ATF6, IRE1α, CHOP, caspase‑3 and caspase‑12 in pancreatic cancer BxPC‑3 cell‑derived xenograft tumors.
    Mol Med Rep 2017 May 22;15(5):3259-3263. Epub 2017 Mar 22.
    Tumor Research Center of Integrative Medicine, Changhua Christian Hospital, Changhua 500‑06, Taiwan, R.O.C.
    Tanshinone (Tan)-IIA is a derivative of phenanthrenequinone and the main active ingredient isolated from Salviae miltiorrhizae radix (Danshen). Previous studies have demonstrated that Tan‑IIA increased the protein expressions levels of protein kinase RNA‑like endoplasmic reticulum kinase (PERK), activating transcription factor (ATF) 6, caspase‑12 and CCAAT‑enhancer‑binding protein homologous protein (CHOP), to induce endoplasmic reticulum (ER) stress and apoptosis in human pancreatic cancer BxPC‑3 cells. However, to the best of our knowledge, the effects of Tan‑IIA on pancreatic cancer cells have not been investigated in vivo. Read More

    Therapeutic Drug Monitoring of Continuous Infusion Doripenem in a Pediatric Patient on Continuous Renal Replacement Therapy.
    J Pediatr Pharmacol Ther 2017 Jan-Feb;22(1):69-73
    An 11-year-old African American male with severe combined immunodeficiency variant, non-cystic fibrosis bronchiectasis, pancreatic insufficiency, chronic mycobacterium avium-intracellulare infection, chronic sinusitis, and malnutrition presented with a 1-week history of fevers. He subsequently developed respiratory decompensation and cefepime was discontinued and doripenem was initiated. Doripenem was the carbapenem used due to a national shortage of meropenem. Read More

    Reticular dysgenesis: international survey on clinical presentation, transplantation and outcome.
    Blood 2017 Mar 22. Epub 2017 Mar 22.
    Biotherapy Clinical Investigation Center, Hopital Necker Enfants Malades, Paris, France.
    Reticular Dysgenesis (RD) is a rare congenital disorder defined clinically by the combination of severe combined immunodeficiency (SCID), agranulocytosis and sensorineural deafness. Mutations in the gene encoding Adenylate Kinase 2 (AK2) were identified to cause the disorder. Hematopoietic stem cell transplantation (HSCT) is the only option to cure this otherwise fatal disease. Read More

    Limiting Thymic Precursor Supply Increases the Risk of Lymphoid Malignancy in Murine X-Linked Severe Combined Immunodeficiency.
    Mol Ther Nucleic Acids 2017 Mar 10;6:1-14. Epub 2016 Dec 10.
    Gene Therapy Research Unit, Children's Medical Research Institute, The University of Sydney and The Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia; Discipline of Child and Adolescent Health, The University of Sydney, Westmead, NSW 2145, Australia. Electronic address:
    In early gene therapy trials for SCID-X1, using γ-retroviral vectors, T cell leukemias developed in a subset of patients secondary to insertional proto-oncogene activation. In contrast, we have reported development of T cell leukemias in SCID-X1 mice following lentivirus-mediated gene therapy independent of insertional mutagenesis. A distinguishing feature in our study was that only a proportion of transplanted γc-deficient progenitors were transduced and therefore competent for reconstitution. Read More

    Good Laboratory Practice Preclinical Safety Studies for GSK2696273 (MLV Vector-Based Ex Vivo Gene Therapy for Adenosine Deaminase Deficiency Severe Combined Immunodeficiency) in NSG Mice.
    Hum Gene Ther Clin Dev 2017 Mar;28(1):17-27
    1 Pathogenesis and Therapy of Primary Immunodeficiencies Unit, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) , IRCCS San Raffaele Scientific Institute, Milan, Italy.
    GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients. Read More

    Incidence of typically Severe Primary Immunodeficiency Diseases in Consanguineous and Non-consanguineous Populations.
    J Clin Immunol 2017 Apr 16;37(3):295-300. Epub 2017 Mar 16.
    Soroka University Medical Center, 84101, Beer-Sheva, Israel.
    Purpose: Primary immunodeficiency diseases are considered to be rare diseases; however, data on the exact birth incidences of these diseases are sparse. Southern Israel is inhabited by two major populations: a relatively non-consanguineous Jewish population and a highly consanguineous Muslim Bedouin population. We sought to calculate the incidences of typically severe primary immunodeficiency diseases and compare the incidences in these populations. Read More

    [Primary immunodeficiencies in seriously ill children: Report of 3 clinical cases].
    Rev Chil Pediatr 2017 02;88(1):136-141
    Unidad de Paciente Crítico Pediátrico, Clínica Santa María, Santiago, Chile.
    Primary immunodeficiency diseases (PID) are congenital disorders secondary to an impaired immune response. Infections, autoimmune disorders, atopy, and lymphoproliferative syndromes are commonly associated with this disorder.

    Objective: To present and discuss 3 infants diagnosed with PID. Read More

    Treatment of infants identified as having severe combined immunodeficiency by means of newborn screening.
    J Allergy Clin Immunol 2017 Mar;139(3):733-742
    Department of Pediatrics, Division of Allergy, Immunology, and Bone Marrow Transplantation, University of California, San Francisco, Calif.
    Severe combined immunodeficiency (SCID) is characterized by severely impaired T-cell development and is fatal without treatment. Newborn screening (NBS) for SCID permits identification of affected infants before development of opportunistic infections and other complications. Substantial variation exists between treatment centers with regard to pretransplantation care, and transplantation protocols for NBS identified infants with SCID, as well as infants with other T-lymphopenic disorders detected by using NBS. Read More

    New frontiers in the therapy of primary immunodeficiency: From gene addition to gene editing.
    J Allergy Clin Immunol 2017 Mar;139(3):726-732
    Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Calif.
    The most severe primary immune deficiency diseases (PIDs) have been successfully treated with allogeneic hematopoietic stem cell transplantation for more than 4 decades. However, such transplantations have the best outcomes when there is a well-matched donor available because immune complications, such as graft-versus-host disease, are greater without a matched sibling donor. Gene therapy has been developed as a method to perform autologous transplantations of a patient's own stem cells that are genetically corrected. Read More

    Low-frequency ultrasound radiosensitization and therapy response monitoring of tumors: an in vivo study.
    Conf Proc IEEE Eng Med Biol Soc 2016 Aug;2016:3227-3230
    A new framework has been introduced in this paper for tumor radiosensitization and therapy response monitoring using low-frequency ultrasound. Human fibrosarcoma xenografts grown in severe combined immunodeficiency (SCID) mice (n = 108) were treated using ultrasound-stimulated microbubbles at various concentration and exposed to different doses of radiation. Low-frequency ultrasound radiofrequency (RF) data were acquired from tumors prior to and at different times after treatment. Read More

    Clinical, Laboratory and Molecular Findings of 63 Patients with Severe Combined Immunodeficiency: A Decade´s Experience.
    J Investig Allergol Clin Immunol 2017 Mar 7. Epub 2017 Mar 7.
    Immunology Asthma and Allergy Research Institute (IAARI),Tehran University of Medical Sciences, Tehran, Iran.
    Background:: Severe combined immunodeficiency (SCID) is known as a pediatric emergency disease with life threatening conditions. This is an exclusive report of clinical evaluation, immunological assessment, molecular analysis and outcomes of SCID patients in a tertiary referral center in Iran.

    Methods: During January 2006 and December 2015, in a prospective cohort study, initial screening and advanced immunological tests were carried out on patients suspected of having SCID. Read More

    Gene therapy for primary immune deficiencies: a Canadian perspective.
    Allergy Asthma Clin Immunol 2017 27;13:14. Epub 2017 Feb 27.
    Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, ON Canada.
    The use of gene therapy (GT) for the treatment of primary immune deficiencies (PID) including severe combined immune deficiency (SCID) has progressed significantly in the recent years. In particular, long-term studies have shown that adenosine deaminase (ADA) gene delivery into ADA-deficient hematopoietic stem cells that are then transplanted into the patients corrects the abnormal function of the ADA enzyme, which leads to immune reconstitution. In contrast, the outcome was disappointing for patients with X-linked SCID, Wiskott-Aldrich syndrome and chronic granulomatous disease who received GT followed by autologous gene corrected transplantations, as many developed hematological malignancies. Read More

    Dickkopf-related protein 3 negatively regulates the osteogenic differentiation of rat dental follicle cells.
    Mol Med Rep 2017 Apr 3;15(4):1673-1681. Epub 2017 Feb 3.
    Department of Operative Dentistry and Endodontics, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China.
    The present study aimed to investigate the effect of Dickkopf-related protein 3 (DKK3) on osteogenic differentiation of rat dental follicle cells (DFCs). A PCR array analysis of Wnt pathway activation in DFCs identified genes dysregulated by mineral induction. Among them, DKK3expression levels were decreased, and further experiments were conducted to investigate its role in DFC osteogenesis. Read More

    Interferon alpha treatment stimulates interferon gamma expression in type I NKT cells and enhances their antiviral effect against hepatitis C virus.
    PLoS One 2017 2;12(3):e0172412. Epub 2017 Mar 2.
    Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
    Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-α using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs). Read More

    Potential of Cannabidiol for the Treatment of Viral Hepatitis.
    Pharmacognosy Res 2017 Jan-Mar;9(1):116-118
    Department of Basic Medical Sciences, University of the West Indies, Mona, Jamaica.
    Viral hepatitis B (HBV) and hepatitis C (HCV) pose a major health problem globally and if untreated, both viruses lead to severe liver damage resulting in liver cirrhosis and cancer. While HBV has a vaccine, HCV has none at the moment. The risk of drug resistance, combined with the high cost of current therapies, makes it a necessity for cost-effective therapeutics to be discovered and developed. Read More

    Primary immunodeficiency diseases in Northern Iran.
    Allergol Immunopathol (Madr) 2017 May - Jun;45(3):244-250. Epub 2017 Feb 22.
    Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Boston, MA, USA. Electronic address:
    Introduction: Primary immunodeficiency diseases (PID) are a heterogeneous group of inherited disorders, characterised by recurrent severe infections, autoimmunity and lymphoproliferation. Despite impressive progress in identification of novel PID, there is an unfortunate lack of awareness among physicians in identification of patients with PID, especially in non-capital cities of countries worldwide.

    Result: This study was performed in a single-centre paediatric hospital in Northern Iran during a 21-year period (1994-2015). Read More

    Molecular determinants for STIM1 activation during store-operated Ca2+ entry.
    Curr Mol Med 2017 Feb 19. Epub 2017 Feb 19.
    Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, 2121 W Holcombe Blvd, Houston, TX 77030, United States.
    Background: STIM/ORAI-mediated store-operated Ca2+ entry (SOCE) mediates a myriad of Ca2+-dependent cellular activities in mammals. Genetic defects in STIM1/ORAI1 lead to devastating severe combined immunodeficiency; whereas gain-of-function mutations in STIM1/ORAI1 are intimately associated with tubular aggregate myopathy. At molecular level, a decrease in the Ca2+ concentrations within the lumen of endoplasmic reticulum (ER) initiates multimerization of the STIM1 luminal domain to switch on the STIM1 cytoplasmic domain to engage and gate ORAI channels, thereby leading to the ultimate Ca2+ influx from the extracellular space into the cytosol. Read More

    The distribution of the apparent diffusion coefficient as an indicator of the response to chemotherapeutics in ovarian tumour xenografts.
    Sci Rep 2017 Feb 21;7:42905. Epub 2017 Feb 21.
    Queensland University of Technology (QUT), Brisbane, Queensland (QLD), Australia.
    Diffusion-weighted magnetic resonance imaging (DW-MRI) was used to evaluate the effects of single-agent and combination treatment regimens in a spheroid-based animal model of ovarian cancer. Ovarian tumour xenografts grown in non-obese diabetic/severe-combined-immunodeficiency (NOD/SCID) mice were treated with carboplatin or paclitaxel, or combination carboplatin/paclitaxel chemotherapy regimens. After 4 weeks of treatment, tumours were extracted and underwent DW-MRI, mechanical testing, immunohistochemical and gene expression analyses. Read More

    Long-term outcome of hematopoietic stem cell transplantation for IL2RG/JAK3 SCID: a cohort report.
    Blood 2017 Apr 16;129(15):2198-2201. Epub 2017 Feb 16.
    Pediatric Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Hematopoietic stem cell transplantation (HSCT) cures the T-lymphocyte, B-lymphocyte, and natural killer (NK)-cell differentiation defect in interleukin-2 γ-chain receptor (IL2RG)/JAK3 severe combined immunodeficiency (SCID). We evaluated long-term clinical features, longitudinal immunoreconstitution, donor chimerism, and quality of life (QoL) of IL2RG/JAK3 SCID patients >2 years post-HSCT at our center. Clinical data were collated and patients/families answered PedsQL Generic Core Scale v4. Read More

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