8,116 results match your criteria Severe Combined Immunodeficiency


The γ Family of Cytokines: Basic Biology to Therapeutic Ramifications.

Immunity 2019 Apr;50(4):832-850

Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Metabolic, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1674, USA. Electronic address:

The common cytokine receptor γ chain, γ, is a component of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. Mutation of the gene encoding γ results in X-linked severe combined immunodeficiency in humans, and γ family cytokines collectively regulate development, proliferation, survival, and differentiation of immune cells. Here, we review the basic biology of these cytokines, highlighting mechanisms of signaling and gene regulation that have provided insights for immunodeficiency, autoimmunity, allergic diseases, and cancer. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613193014
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http://dx.doi.org/10.1016/j.immuni.2019.03.028DOI Listing
April 2019
5 Reads

Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1.

N Engl J Med 2019 04;380(16):1525-1534

From the Departments of Bone Marrow Transplantation and Cellular Therapy (E.M., B.T., W.J., S.G.), Hematology (S.Z., Z.M., J.C., J.D., X.T., B.Y.R., M.J.W., B.P.S.), Therapeutics Production and Quality (T.L., M.M.M.), Immunology (H.A., B.Y.), Pharmaceutical Sciences (S.J.C.), Biostatistics (G.K., C.L.), and Infectious Diseases (G.M.), St. Jude Children's Research Hospital, Memphis, TN; the Allergy and Clinical Immunology Division, Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru (J.C.A.B.); the Department of Pediatrics, Allergy-Immunology Division, Children's Hospital Los Angeles, Los Angeles (J.A.C.), and the Department of Pediatrics, Division of Pediatric Allergy-Immunology-Bone Marrow Transplantation, University of California, San Francisco (UCSF) Benioff Children's Hospital, San Francisco (J.R.L.-B., J.M.P., M.J.C.) - both in California; the Department of Pediatrics, Pediatric Allergy and Immunology, University of New Mexico, Albuquerque (E.D.); University of Oklahoma Health Sciences Center, Tulsa (J.T.L.); Departamento de Pediatria da Universidade de Taubaté, Conselho Nacional de Medicina, São Paulo (A.C.M.A.); Copperfield Childcare, Claremont, South Africa (H.W.); and the Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (S.S.D.R., H.L.M.).

Background: Allogeneic hematopoietic stem-cell transplantation for X-linked severe combined immunodeficiency (SCID-X1) often fails to reconstitute immunity associated with T cells, B cells, and natural killer (NK) cells when matched sibling donors are unavailable unless high-dose chemotherapy is given. In previous studies, autologous gene therapy with γ-retroviral vectors failed to reconstitute B-cell and NK-cell immunity and was complicated by vector-related leukemia.

Methods: We performed a dual-center, phase 1-2 safety and efficacy study of a lentiviral vector to transfer complementary DNA to bone marrow stem cells after low-exposure, targeted busulfan conditioning in eight infants with newly diagnosed SCID-X1. Read More

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http://www.nejm.org/doi/10.1056/NEJMoa1815408
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http://dx.doi.org/10.1056/NEJMoa1815408DOI Listing
April 2019
6 Reads

Impulsivity differences between bipolar and unipolar depression.

Indian J Psychiatry 2019 Mar-Apr;61(2):156-160

Department of Psychiatry, Faculty of Medicine, Sakarya University, Sakarya, Turkey.

Background: Even though particularly bipolar depression and unipolar depression seem to be similar, they show differences in terms of the etiology, phenomenology, course, and treatment process. Bipolar depression is associated with mood lability, motor retardation, and hypersomnia to a larger extent. Early age of onset, a high frequency of depressive episodes, and history of bipolar disease in the family are suggestive of bipolar disorder (BD) rather than major depression. Read More

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http://dx.doi.org/10.4103/psychiatry.IndianJPsychiatry_166_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425788PMC
April 2019
1 Read

Progressive Immunodeficiency with Gradual Depletion of B and CD4⁺ T Cells in Immunodeficiency, Centromeric Instability and Facial Anomalies Syndrome 2 (ICF2).

Diseases 2019 Apr 4;7(2). Epub 2019 Apr 4.

Department of Clinical Immunology and Rheumatology, Hannover Medical School, 30625 Hannover, Germany.

Immunodeficiency, centromeric instability and facial anomalies syndrome 2 (ICF2) is a rare autosomal recessive primary immunodeficiency disorder. So far, 27 patients have been reported. Here, we present three siblings with ICF2 due to a homozygous ZBTB24 gene mutation (c. Read More

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http://dx.doi.org/10.3390/diseases7020034DOI Listing
April 2019
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Outcomes of Related and Unrelated Donor Searches Among Patients with Primary Immunodeficiency Diseases Referred for Allogeneic Hematopoietic Cell Transplantation.

Biol Blood Marrow Transplant 2019 Apr 12. Epub 2019 Apr 12.

National Institutes of Health, Bethesda, Maryland. Electronic address:

Introduction: Patients with primary immunodeficiencies (PIDs) are potentially cured by allogeneic hematopoietic cell transplantation (HCT). The spectrum of PIDs has expanded greatly beyond those that present in infancy or are diagnosed on newborn screening and require urgent, preemptive HCT. Many PID diagnoses are now made later in life and the role of HCT is only considered upon severe disease manifestations; in these cases, the kinetics and goals of a donor search may be different than for severe combined immunodeficiency. Read More

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http://dx.doi.org/10.1016/j.bbmt.2019.04.008DOI Listing
April 2019
1 Read

Pharmacological blockade of the CD39/CD73 pathway but not adenosine receptors augments disease in a humanised mouse model of graft-versus-host disease.

Immunol Cell Biol 2019 Apr 7. Epub 2019 Apr 7.

School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW, 2252, Australia.

Allogeneic haematopoietic stem cell transplantation (HSCT) is a curative therapy for a number of haematological malignancies, but is limited by the development of graft-versus-host disease (GVHD). CD39 and CD73 form an ecto-enzymatic pathway that hydrolyses extracellular adenosine 5'-triphosphate (ATP) to adenosine, which respectively exacerbate or alleviate disease in allogeneic mouse models of GVHD. The current study aimed to explore the role of the CD39/CD73 pathway and adenosine receptor (AR) blockade in a humanised mouse model of GVHD. Read More

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http://dx.doi.org/10.1111/imcb.12251DOI Listing
April 2019
2 Reads

Clinical and economic aspects of newborn screening for severe combined immunodeficiency: DEPISTREC study results.

Clin Immunol 2019 Apr 1;202:33-39. Epub 2019 Apr 1.

Laboratoire d'Immunologie, CHU Nantes, Nantes, France.

Purpose: Severe combined immunodeficiency (SCID) refers to a group of genetic disorders characterized by greatly compromised cellular and humoral immunity. Children with SCID are asymptomatic at birth, but they die from infections within the first months of life if not treated. Quantification of T-cell receptor excision circles is an extremely sensitive screening method for detecting newborns who may have SCID. Read More

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http://dx.doi.org/10.1016/j.clim.2019.03.012DOI Listing
April 2019
1 Read

Are peptides a solution for the treatment of hyperactivated JAK3 pathways?

Inflammopharmacology 2019 Mar 30. Epub 2019 Mar 30.

Cell Culture Laboratory, Post-Graduation Program in Biotechnology, University of Vale do Taquari-UNIVATES, Av. Avelino Tallini, 171, Lajeado, RS, 95914-014, Brazil.

While the inactivation mutations that eliminate JAK3 function lead to the immunological disorders such as severe combined immunodeficiency, activation mutations, causing constitutive JAK3 signaling, are known to trigger various types of cancer or are responsible for autoimmune diseases, such as rheumatoid arthritis, psoriasis, or inflammatory bowel diseases. Treatment of hyperactivated JAK3 is still an obstacle, due to different sensibility of mutation types to conventional drugs and unwanted side effects, because these drugs are not absolutely specific for JAK3, thus inhibiting other members of the JAK family, too. Lack of information, in which way sole inhibition of JAK3 is necessary for elimination of the disease, calls for the development of isoform-specific JAK3 inhibitors. Read More

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http://dx.doi.org/10.1007/s10787-019-00589-2DOI Listing
March 2019
2 Reads

Celastrol induce apoptosis of human multiple myeloma cells involving inhibition of proteasome activity.

Eur J Pharmacol 2019 Mar 27;853:184-192. Epub 2019 Mar 27.

School of Pharmacy, Chengdu Medical College, Chengdu, China; Center for Scientific Research, Chengdu Medical College, Chengdu, China. Electronic address:

Celastrol exhibits anticancer activity and has a number of potential molecular targets. Among them, the proteasome has attracted particular attention. Although celastrol inhibits multiple myeloma (MM) cell proliferation, the induction of proteasome-inhibitory activity by celastrol in MM cells at the cellular level and in tumors of mice bearing xenografts has not been confirmed. Read More

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http://dx.doi.org/10.1016/j.ejphar.2019.03.036DOI Listing
March 2019
2 Reads

Characterization of pulmonary intimal sarcoma cells isolated from a surgical specimen: In vitro and in vivo study.

PLoS One 2019 29;14(3):e0214654. Epub 2019 Mar 29.

Department of Respirology (B2), Graduate School of Medicine, Chiba University, Chiba City, Japan.

Pulmonary intimal sarcoma (PIS) constitutes a rare sarcoma originating from the intimal cells of pulmonary arteries. The pathogenesis of PIS remains to be elucidated and specific treatments have not been established; therefore, prognosis is generally poor. The purpose of our study was to isolate and characterize PIS cells from a specimen resected from a patient with PIS. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214654PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440640PMC
March 2019
4 Reads

Clinical Features and HSCT Outcome for SCID in Turkey.

J Clin Immunol 2019 Mar 28. Epub 2019 Mar 28.

Department of Pediatric Immunology, Hacettepe University Medical School, Ankara, Turkey.

Severe combined immunodeficiency (SCID) is the most serious PID, characterized by T cell lymphopenia and lack of antigen-specific T cell and B cell immune responses, inevitably leading to death within the first year of life if hematopoietic stem cell transplantation (HSCT) is not performed.

Purpose And Methods: Since SCID is a common type of PID with an estimated incidence of 1/10.000 in Turkey, a retrospective analysis of HSCT characteristics, survival, immune recovery, and the major clinical features of SCID prior to HSCT is the aim of this multi-transplant center-based analysis. Read More

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http://dx.doi.org/10.1007/s10875-019-00610-xDOI Listing
March 2019
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Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in HIV infection: a metabolic approach of an infectious disease.

Expert Rev Gastroenterol Hepatol 2019 Mar 23:1-10. Epub 2019 Mar 23.

a Liver Research Unit , Medica Sur Clinic & Foundation , Mexico City , Mexico.

Introduction: With the successes of antiretroviral therapy, patients infected with human immunodeficiency virus (HIV) living longer. Regarding this, the common diseases of HIV population (i.e. Read More

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http://dx.doi.org/10.1080/17474124.2019.1599284DOI Listing
March 2019
1 Read
2.546 Impact Factor

Alternative Splicing Rescues Loss of Common Gamma Chain Function and Results in IL-21R-like Deficiency.

J Clin Immunol 2019 Feb 21;39(2):207-215. Epub 2019 Mar 21.

Dr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital, LMU Munich, Lindwurmstrasse 4, 80337, Munich, Germany.

Inborn errors in interleukin 2 receptor, gamma (IL2RG) perturb signaling of the common gamma chain family cytokines and cause severe combined immunodeficiency (SCID). Here, we report two brothers suffering from chronic cryptosporidiosis, severe diarrhea, and cholangitis. Pan T, B, and NK cell numbers were normal, but immunophenotyping revealed defective B cell differentiation. Read More

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http://dx.doi.org/10.1007/s10875-019-00606-7DOI Listing
February 2019
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A Novel FOXN1 Variant Is Identified in Two Siblings with Nude Severe Combined Immunodeficiency.

J Clin Immunol 2019 Feb 22;39(2):144-147. Epub 2019 Mar 22.

Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.

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http://dx.doi.org/10.1007/s10875-019-00615-6DOI Listing
February 2019
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Reconstruction of the ovary microenvironment utilizing macroporous scaffold with affinity-bound growth factors.

Biomaterials 2019 Jun 14;205:11-22. Epub 2019 Mar 14.

Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel; Regenerative Medicine and Stem Cell (RMSC) Research Center, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel; The Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel. Electronic address:

Implementing ovarian tissue engineering for the maturation of primordial follicles, the most abundant follicle population in the ovary, holds great potential for women fertility preservation. Here, we evaluated whether macroporous alginate scaffolds with affinity-bound bone morphogenetic protein-4 (BMP-4) could mimic the ovary microenvironment and support the culture and growth of primordial follicles seeded with supporting ovarian cells. Porcine primordial follicles developed in the alginate scaffolds up to the pre-antral stage within 21 days. Read More

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http://dx.doi.org/10.1016/j.biomaterials.2019.03.013DOI Listing
June 2019
10 Reads

An immunocompetent patient with a nonsense mutation in NHEJ1 gene.

BMC Med Genet 2019 Mar 21;20(1):45. Epub 2019 Mar 21.

Persian BayanGene Research and Training Center, Shiraz, Iran.

Background: DNA double-strand breaks (DSBs) are among the most deleterious types of DNA damage. DSBs are repaired by homologous recombination or non-homologous end-joining (NHEJ). NHEJ, which is central to the process of V(D)J recombination is the principle pathway for DSB repair in higher eukaryotes. Read More

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http://dx.doi.org/10.1186/s12881-019-0784-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429708PMC
March 2019
1 Read

MYB promotes the growth and metastasis of salivary adenoid cystic carcinoma.

Int J Oncol 2019 May 18;54(5):1579-1590. Epub 2019 Mar 18.

Central Laboratory, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 10081, P.R. China.

The incidence of recurrent t(6;9) translocation of the MYB proto‑oncogene to NFIB (the gene that encodes nuclear factor 1 B‑type) in adenoid cystic carcinoma (ACC) tumour tissues is high. However, MYB [the gene that encodes transcriptional activator Myb (MYB)] overexpression is more common, indicating that MYB serves a key role in ACC. The current study aimed to investigate the role of MYB in salivary (S)ACC growth and metastasis. Read More

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http://www.spandidos-publications.com/10.3892/ijo.2019.4754
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http://dx.doi.org/10.3892/ijo.2019.4754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438425PMC
May 2019
7 Reads

Chromosome Transplantation: Correction of the Chronic Granulomatous Disease Defect in Mouse Induced Pluripotent Stem Cells.

Stem Cells 2019 Mar 20. Epub 2019 Mar 20.

National Research Council (CNR)-IRGB/UOS of Milan, Milan, Italy.

In spite of the progresses in gene editing achieved in recent years, a subset of genetic diseases involving structural chromosome abnormalities, including aneuploidies, large deletions and complex rearrangements, cannot be treated with conventional gene therapy approaches. We have previously devised a strategy, dubbed chromosome transplantation (CT), to replace an endogenous mutated chromosome with an exogenous normal one. To establish a proof of principle for our approach, we chose as disease model the chronic granulomatous disease (CGD), an X-linked severe immunodeficiency due to abnormalities in CYBB (GP91) gene, including large genomic deletions. Read More

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http://dx.doi.org/10.1002/stem.3006DOI Listing
March 2019
3 Reads

The First Purine Nucleoside Phosphorylase Deficiency Patient Resembling IgA Deficiency and a Review of the Literature.

Immunol Invest 2019 Mar 19:1-21. Epub 2019 Mar 19.

a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran, and the University of Medical Science , Tehran , Iran.

Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive primary immunodeficiency disorder characterized by decreased numbers of T-cells, variable B-cell abnormalities, decreased amount of serum uric acid and PNP enzyme activity. The affected patients usually present with recurrent infections, neurological dysfunction and autoimmune phenomena. In this study, whole-exome sequencing was used to detect mutation in the case suspected of having primary immunodeficiency. Read More

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https://www.tandfonline.com/doi/full/10.1080/08820139.2019.1
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http://dx.doi.org/10.1080/08820139.2019.1570249DOI Listing
March 2019
3 Reads
1.903 Impact Factor

Establishment of cell line and in vivo mouse model of canine Langerhans cell histiocytosis.

Vet Comp Oncol 2019 Mar 18. Epub 2019 Mar 18.

Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.

A cell line named FB-LCH01, derived from a dog diagnosed with Langerhans cell histiocytosis, was established and characterized. FB-LCH01 had C-shaped nucleoli, characterized by modal chromosome aberrations. The original tumor cells as well as established FB-LCH01 cells were immunopositive for HLA-DR, Iba-1 and E-cadherin, and immunonegative for CD163 and CD204, suggesting Langerhans cell origin. Read More

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http://dx.doi.org/10.1111/vco.12476DOI Listing
March 2019
1 Read

Lymphopenia and Severe Combined Immunodeficiency (SCID) - Think Before You Ink.

Indian J Pediatr 2019 Mar 16. Epub 2019 Mar 16.

Department of Pediatric Immunology and Leukocyte Biology, National Institute of Immunohematology (ICMR), Mumbai, Maharashtra, India.

Objectives: Severe combined immunodeficiency (SCID) represents one of the most severe forms of Primary immunodeficiency (PID) disorders, characterized by T cell lymphopenia (TCL) and lack of cellular and humoral immune responses. However, not all patients with low T cell lymphocyte counts may have an abnormal T cell immunity and the observed TCL may be a temporary suppression resulting from transient lymphopenia secondary to severe infections. In such cases, it is necessary to estimate the severity of the observed TCL by assessing thymic capabilities. Read More

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http://dx.doi.org/10.1007/s12098-019-02904-9DOI Listing
March 2019
2 Reads

Low Exposure Busulfan Conditioning to Achieve Sufficient Multilineage Chimerism in Patients with Severe Combined Immunodeficiency.

Biol Blood Marrow Transplant 2019 Mar 12. Epub 2019 Mar 12.

Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco Benioff Children's Hospital, San Francisco, California.

After allogeneic hematopoietic cell transplantation (HCT), the minimal myeloid chimerism required for full T and B cell reconstitution in patients with severe combined immunodeficiency (SCID) is unknown. We retrospectively reviewed our experience with low-exposure busulfan (cumulative area under the curve, 30 mg·hr/L) in 10 SCID patients undergoing either first or repeat HCT from unrelated or haploidentical donors. The median busulfan dose required to achieve this exposure was 5. Read More

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http://dx.doi.org/10.1016/j.bbmt.2019.03.008DOI Listing
March 2019
2 Reads

Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease.

Genes (Basel) 2019 Mar 14;10(3). Epub 2019 Mar 14.

Stead Family Department of Pediatrics, The University of Iowa, Iowa City, IA 52242, USA.

Despite the continued development of cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs for the treatment of cystic fibrosis (CF), the need for mutation agnostic treatments remains. In a sub-group of CF individuals with mutations that may not respond to modulators, such as those with nonsense mutations, CFTR gene transfer to airway epithelia offers the potential for an effective treatment. Lentiviral vectors are well-suited for this purpose because they transduce nondividing cells, and provide long-term transgene expression. Read More

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http://dx.doi.org/10.3390/genes10030218DOI Listing
March 2019
1 Read

The R229Q mutation of Rag2 does not characterize severe immunodeficiency in mice.

Sci Rep 2019 Mar 14;9(1):4415. Epub 2019 Mar 14.

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.

RAG1 or RAG2 mutations are associated with defects in V(D)J recombination activity, causing severe immunodeficiency with a wide spectrum of clinical phenotypes. A R229Q mutation of RAG2 was identified in patients with severe combined immunodeficiency (SCID) or Omenn syndrome (OS). Although some factors determining the clinical features between SCID and OS were not clear, the molecular mechanism of OS was studied in a mouse model in which an EGFP tag is fused to Rag2 with the R229Q mutation. Read More

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http://dx.doi.org/10.1038/s41598-019-39496-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418226PMC
March 2019
2 Reads

MTBVAC-Based TB-HIV Vaccine Is Safe, Elicits HIV-T Cell Responses, and Protects against in Mice.

Mol Ther Methods Clin Dev 2019 Jun 7;13:253-264. Epub 2019 Feb 7.

AIDS Research Group, Hospital Clínic de Barcelona/IDIBAPS-HIVACAT, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain.

The tuberculosis (TB) vaccine MTBVAC is the only live-attenuated ()-based vaccine in clinical development, and it confers superior protection in different animal models compared to the current vaccine, BCG ( bacillus Calmette-Guérin). With the aim of using MTBVAC as a vector for a dual TB-HIV vaccine, we constructed the recombinant MTBVAC.HIVA strain. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S23290501193001
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http://dx.doi.org/10.1016/j.omtm.2019.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395831PMC
June 2019
5 Reads

A synonymous splice site mutation in IL2RG gene causes late-onset combined immunodeficiency.

Int J Hematol 2019 Mar 8. Epub 2019 Mar 8.

Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

X-Linked severe combined immunodeficiency (X-SCID) is a severe form of primary immunodeficiency characterized by absence of T cells and NK cells. X-SCID is caused by a loss-of-function mutation in the IL2RG gene that encodes common gamma chain (γc), which plays an essential role in lymphocyte development. We report the first case of hypomorphic X-SCID caused by a synonymous mutation in the IL2RG gene leading to a splice anomaly, in a family including two patients with diffuse cutaneous warts, recurrent molluscum contagiosum, and mild respiratory infections. Read More

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http://dx.doi.org/10.1007/s12185-019-02619-9DOI Listing
March 2019
1 Read

Cytoplasmic Interactions between the Glucocorticoid Receptor and HDAC2 Regulate Osteocalcin Expression in VPA-Treated MSCs.

Cells 2019 Mar 5;8(3). Epub 2019 Mar 5.

Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20133 Milan, Italy.

Epigenetic regulation has been considered an important mechanism for influencing stem cell differentiation. In particular, histone deacetylases (HDACs) have been shown to play a role in the osteoblast differentiation of mesenchymal stem cells (MSCs). In this study, the effect of the HDAC inhibitor, valproic acid (VPA), on bone formation in vivo by MSCs was determined. Read More

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http://dx.doi.org/10.3390/cells8030217DOI Listing
March 2019
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Human DOCK2 Deficiency: Report of a Novel Mutation and Evidence for Neutrophil Dysfunction.

J Clin Immunol 2019 Mar 5. Epub 2019 Mar 5.

Laboratory for Inborn Errors of Immunity, Department of Immunology and Microbiology, KU Leuven, Leuven, EU, Belgium.

DOCK2 is a guanine-nucleotide-exchange factor for Rac proteins. Activated Rac serves various cellular functions including the reorganization of the actin cytoskeleton in lymphocytes and neutrophils and production of reactive oxygen species in neutrophils. Since 2015, six unrelated patients with combined immunodeficiency and early-onset severe viral infections caused by bi-allelic loss-of-function mutations in DOCK2 have been described. Read More

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http://dx.doi.org/10.1007/s10875-019-00603-wDOI Listing
March 2019
9 Reads

Hematopoietic Stem Cell Transplantation Beyond Severe Combined Immunodeficiency: Seeking a Cure for Primary Immunodeficiency.

Authors:
Richard Mitchell

J Allergy Clin Immunol Pract 2019 Mar;7(3):776-785

Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia; School of Women and Children's Health, University of New South Wales, Sydney, New South Wales, Australia. Electronic address:

Hematopoietic stem cell transplantation (HSCT) can provide definitive therapy for patients with primary immunodeficiency disease (PIDD). Modern HSCT techniques and supportive care have significantly improved outcomes for patients with PIDD. This review examines current HSCT practice for PIDD other than severe combined immunodeficiency, and explores indications, risks, and long-term outcomes for this group of challenging diseases. Read More

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http://dx.doi.org/10.1016/j.jaip.2018.12.011DOI Listing
March 2019
1 Read

Purine Nucleoside Phosphorylate Deficiency Severe Combined Immunodeficiency in an Infant: Subtle Diagnostic Clues.

Indian Pediatr 2019 Feb;56(2):146

Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, PGIMER, Chandigarh, India.

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February 2019

Long noncoding RNA regulates tumor cell proliferation and invasion by epithelial-mesenchymal transition in gastric cancer.

Therap Adv Gastroenterol 2019 19;12:1756284819827697. Epub 2019 Feb 19.

Department of General Surgery & Institute of General Surgery, Chinese People's Liberation Army General Hospital, Fuxing Road 28, Beijing 100853, PR China.

Background: The clinical relevance and biological role of tissular in gastric cancer (GC) remains to be clarified.

Methods: The association between expression and clinicopathological characteristics was investigated. , 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to explore the biological effects of on GC cell proliferation, migration, invasion, and apoptosis in MGC-803 and BGC-823 cell lines. Read More

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http://dx.doi.org/10.1177/1756284819827697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383096PMC
February 2019
2 Reads

Cost-effectiveness of newborn screening for severe combined immunodeficiency.

Eur J Pediatr 2019 May 25;178(5):721-729. Epub 2019 Feb 25.

Department of Medical Decision Making, Leiden University Medical Center, PO box 9600, 2300 RC, Leiden, The Netherlands.

Severe combined immunodeficiency (SCID) is a condition that often results in severe infections and death at young age. Early detection shortly after birth, followed by treatment before infections occur, largely increases the chances of survival. As the incidence of SCID is low, assessing cost-effectiveness of adding screening for SCID to the newborn screening program is relevant for decision making. Read More

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http://dx.doi.org/10.1007/s00431-019-03346-3DOI Listing
May 2019
1 Read

Recent advances in understanding RAG deficiencies.

Authors:
Andrew Gennery

F1000Res 2019 4;8. Epub 2019 Feb 4.

Paediatric Immunology and Haematopoietic Stem Cell Transplantation, Great North Childrens' Hospital, Newcastle upon Tyne, UK.

Recombination-activating genes ( ) and initiate the molecular processes that lead to lymphocyte receptor formation through VDJ recombination. Nonsense mutations in / cause the most profound immunodeficiency syndrome, severe combined immunodeficiency (SCID). Other severe and less-severe clinical phenotypes due to mutations in genes are now recognized. Read More

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http://dx.doi.org/10.12688/f1000research.17056.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364374PMC
February 2019

Skewed B cell receptor repertoire and reduced antibody avidity in patients with DOCK8 deficiency.

Scand J Immunol 2019 Feb 21:e12759. Epub 2019 Feb 21.

Division of Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China.

DOCK8 immunodeficiency syndrome (DIDS) is a combined immunodeficiency characterized by recurrent viral infections, severe atopy and early onset malignancy. Immunological abnormalities include lymphopenia, CD8 T-cell cytoskeleton dysfunction, defective B cell memory and variable serum immunoglobulin levels. Here, we analyse the B cell receptor repertoire (BCR) characteristics and antibody avidity of four DIDS patients, attempt to understand the dysregulated humoral immunity in DIDS patients with a normal antibody titre and suggest a scientific basis for intravenous immunoglobulin (IVIG) replacement therapy for these patients. Read More

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http://dx.doi.org/10.1111/sji.12759DOI Listing
February 2019

Diminished Ovarian Reserve Chemotherapy-Induced Mouse Model: A Tool for the Preclinical Assessment of New Therapies for Ovarian Damage.

Reprod Sci 2019 Feb 21:1933719119831784. Epub 2019 Feb 21.

1 IVI Foundation, Valencia Spain.

Diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI) are primary factors leading to infertility. However, there is a lack of appropriate animal models of DOR usable for assessing new therapeutic strategies. In this study, we aimed to evaluate whether chemotherapy treatment in mice could reproduce features similar of that observed in women with DOR. Read More

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http://dx.doi.org/10.1177/1933719119831784DOI Listing
February 2019
2 Reads

Impact of Day 14 Peripheral Blood Chimerism after Allogeneic Hematopoietic Stem Cell Bone Transplantation on the Treatment Outcome of Non-Malignant Disease.

J Korean Med Sci 2019 Feb 29;34(6):e46. Epub 2019 Jan 29.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: The impact of early peripheral blood chimerism on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. We aimed to determine whether day 14 peripheral blood chimerism after allo-HSCT predicts outcomes in patients with non-malignant diseases.

Methods: Data from 56 patients who received allo-HSCT between April 2007 and March 2016 were retrospectively analyzed. Read More

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http://dx.doi.org/10.3346/jkms.2019.34.e46DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374552PMC
February 2019
2 Reads

Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India.

Front Immunol 2019 4;10:23. Epub 2019 Feb 4.

Department of Pediatric Immunology and Leukocyte Biology, National Institute of Immunohaematology (ICMR), Mumbai, India.

Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Majority of our patients (89%) presented within 6 months of age. Read More

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http://dx.doi.org/10.3389/fimmu.2019.00023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369708PMC
February 2019
12 Reads

Increased proportions of γδ T lymphocytes in atypical SCID associate with disease manifestations.

Clin Immunol 2019 Apr 15;201:30-34. Epub 2019 Feb 15.

Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Center for Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address:

Severe combined immunodeficiencies (SCID) comprise a group of genetic diseases characterized by abrogated development of T lymphocytes. In some case reports of atypical SCID patients elevated proportions of γδ T lymphocytes have been reported. However, it is unknown whether these γδ T cells modulate or reflect the patient's clinical phenotype. Read More

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http://dx.doi.org/10.1016/j.clim.2018.11.006DOI Listing
April 2019
3 Reads
3.672 Impact Factor

A combined immunodeficiency with severe infections, inflammation, and allergy caused by ARPC1B deficiency.

J Allergy Clin Immunol 2019 Feb 13. Epub 2019 Feb 13.

Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory AMC, University of Amsterdam, Amsterdam, the Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2019.02.003DOI Listing
February 2019
7 Reads
11.476 Impact Factor

Acquired and Innate Immunity Impairment and Severe Disseminated Infection in a Patient With a NF-κB1 Deficiency.

Front Immunol 2018 29;9:3148. Epub 2019 Jan 29.

Research Institute Hospital 12 Octubre (I+12), Madrid, Spain.

NF-κB1 is a master regulator of both acquired and innate responses. loss-of-function mutations elicit a wide clinical phenotype with asymptomatic individuals at one end of the spectrum and patients with common variable immunodeficiency, combined immunodeficiency or autoinflammation at the other. Impairment of acquired and innate immunity and disseminated infection expands the clinical and immunological phenotype of NF-κB1 deficiency. Read More

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http://dx.doi.org/10.3389/fimmu.2018.03148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362422PMC
January 2019
1 Read

Atypical SIFD with novel TRNT1 mutations: a case study on the pathogenesis of B-cell deficiency.

Int J Hematol 2019 Apr 13;109(4):382-389. Epub 2019 Feb 13.

Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

Mutation in the gene encoding tRNA nucleotidyl transferase, CCA-adding 1 (TRNT1), an enzyme essential for the synthesis of the 3'-terminal CCA sequence in tRNA molecules, results in a disorder that features sideroblastic anemia, B-cell immunodeficiency, periodic fever, and developmental delay. Mutations in TRNT1 are also linked to phenotypes including retinitis pigmentosa, cataracts, and cardiomyopathy. To date, it has remained unclear how defective TRNT1 is linked to B-cell deficiency. Read More

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http://link.springer.com/10.1007/s12185-019-02614-0
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http://dx.doi.org/10.1007/s12185-019-02614-0DOI Listing
April 2019
11 Reads

Baboon envelope LVs efficiently transduced human adult, fetal, and progenitor T cells and corrected SCID-X1 T-cell deficiency.

Blood Adv 2019 Feb;3(3):461-475

Centre International de Recherche en Infectiologie, Université Lyon, Université Claude Bernard Lyon 1, INSERM, U1111, Centre National de la Recherche Scientifique, Unité Mixte de Recherche (UMR) 5308, Ecole Normale Supérieure de Lyon, Lyon, France.

T cells represent a valuable tool for treating cancers and infectious and inherited diseases; however, they are mainly short-lived in vivo. T-cell therapies would strongly benefit from gene transfer into long-lived persisting naive T cells or T-cell progenitors. Here we demonstrate that baboon envelope glycoprotein pseudotyped lentiviral vectors (BaEV-LVs) far outperformed other LV pseudotypes for transduction of naive adult and fetal interleukin-7-stimulated T cells. Read More

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http://dx.doi.org/10.1182/bloodadvances.2018027508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373736PMC
February 2019
5 Reads

Increased splenic human CD4:CD8 T cell ratios, serum human interferon-γ and intestinal human interleukin-17 are associated with clinical graft-versus-host disease in humanized mice.

Transpl Immunol 2019 Feb 8. Epub 2019 Feb 8.

School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2252, Australia; Molecular Horizons, University of Wollongong, Wollongong, NSW 2252, Australia; Illawarra Health and Medical Research Institute, Wollongong, NSW 2252, Australia. Electronic address:

Graft-versus-host disease (GVHD) is a frequent complication following allogeneic hematopoietic stem cell transplantation (HSCT) with current therapies limited to general immunosuppression. Humanized mouse models of GVHD are emerging as valuable intermediaries to allow translation of findings from allogeneic mouse models to humans to prevent and treat this disease, but such models require further characterization. In this study, humanized mice were generated by injecting immunodeficient non-obese diabetic severe combined immunodeficiency interleukin (IL)-2 receptor γ common chain null (NSG) mice with human peripheral blood mononuclear cells (hPBMCs). Read More

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http://dx.doi.org/10.1016/j.trim.2019.02.003DOI Listing
February 2019
2 Reads

Fifteen-minute consultation: Recognising primary immune deficiencies in children.

Arch Dis Child Educ Pract Ed 2019 Feb 7. Epub 2019 Feb 7.

Department of Paediatrics, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden.

Children with primary immunodeficiency syndromes present with broad variation of clinical features and the consequences are often severe if not promptly recognised. Here, support is provided for the general paediatrician to recognise primary immunodeficiencies among the many children they meet in their clinical practice. Read More

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http://dx.doi.org/10.1136/archdischild-2018-315484DOI Listing
February 2019
1 Read

Jejuno-jejunal intussusception in a post-lung transplant patient from a gastrojejunostomy tube: A case report.

Int J Surg Case Rep 2019 31;55:129-131. Epub 2019 Jan 31.

Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States. Electronic address:

Introduction: Gastro-jejunostomy tube is used for post-pyloric feeding for critical-ill patient who cannot tolerate oral alimentation. Jejuno-jejunal intussusception is a rare complication of gastrojejunostomy tube.

Presentation Of Case: A 39-year-old male with history of severe combined immunodeficiency, Achalasia and end-stage lung disease underwent double lung transplantation. Read More

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http://dx.doi.org/10.1016/j.ijscr.2019.01.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365386PMC
January 2019
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Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature.

Front Pediatr 2018 21;6:426. Epub 2019 Jan 21.

Immunodeficiencies Research Unit at the National Institute of Pediatrics (INP), Mexico City, Mexico.

DNA repair defects are inborn errors of immunity that result in increased apoptosis and oncogenesis. DNA Ligase 4-deficient patients suffer from a wide range of clinical manifestations since early in life, including: microcephaly, dysmorphic facial features, growth failure, developmental delay, mental retardation; hip dysplasia, and other skeletal malformations; as well as a severe combined immunodeficiency, radiosensitivity, and progressive bone marrow failure; or, they may present later in life with hematological neoplasias that respond catastrophically to chemo- and radiotherapy; or, they could be asymptomatic. We describe the clinical, laboratory, and genetic features of five Mexican patients with LIG4 deficiency, together with a review of 36 other patients available in PubMed Medline. Read More

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http://dx.doi.org/10.3389/fped.2018.00426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348249PMC
January 2019
19 Reads