9,115 results match your criteria Severe Combined Immunodeficiency

BCL10 loss-of-function novel mutation leading to atypical severe combined immunodeficiency.

Clin Immunol 2022 Jun 21:109067. Epub 2022 Jun 21.

Department of Clinical Genetics, Sultan Qaboos University Hospital, Muscat, Oman; Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.

Background: Severe combined immunodeficiency (SCID) is characterized by severe, early-onset infection in infants. B-cell lymphoma/leukemia (BCL) 10 defects causing SCID have been reported previously in two patients.

Material & Methods: A seven-month-old female infant was admitted with bilateral pneumonia requiring ventilatory support. Read More

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Severe Combined Immunodeficiency (SCID) Screening in Arizona: Lessons Learned from the First 2 Years.

J Clin Immunol 2022 Jun 22. Epub 2022 Jun 22.

Center for Cancer and Blood Disorders, Phoenix Children's Hospital, 1919 E. Thomas Road, Phoenix, AZ, 85016, USA.

Purpose: The incidence of severe combined immunodeficiency (SCID) in the USA was reported as 1 in 58,000 live births. In Arizona, it was anticipated that newborn screening would identify two to four cases of SCID per year. This estimate did not consider ethnic nuances in Arizona, with higher percentages of Native American and Hispanic populations compared to national percentages. Read More

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Utility of targeted next generation sequencing for inborn errors of immunity at a tertiary care centre in North India.

Sci Rep 2022 Jun 21;12(1):10416. Epub 2022 Jun 21.

Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Inborn errors of immunity (IEI) are a heterogeneous group of monogenic disorders that include primary immunodeficiency's and other disorders affecting different aspects of the immune system. Next-Generation Sequencing (NGS) is an essential tool to diagnose IEI. We report our 3-year experience in setting up facilities for NGS for diagnosis of IEI in Chandigarh, North India. Read More

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Concomitant Langerhans and Interdigitating Reticulum Cell Hyperplasia in a Reactive Lymph Node of an Infant with Omenn Syndrome: A Diagnostic Pitfall for Langerhans Cell Histiocytosis.

Int J Surg Pathol 2022 Jun 9:10668969221098088. Epub 2022 Jun 9.

Department of Histopathology, 28928Sir Gangaram Hospital, New Delhi, India.

Omenn syndrome, a rare form of combined immunodeficiency in infants, presenting with recurrent infections, erythroderma, lymphadenopathy, hepatosplenomegaly, eosinophilia, and increased serum IgE levels. It is a fatal condition unless treated by hematopoietic stem cell transplant. Hence, an early diagnosis and a prompt treatment can lead to better outcome in these unfortunate babies afflicted with Omenn syndrome. Read More

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Clinical features of very early-onset inflammatory bowel disease in Japan: a retrospective single-center study.

Intest Res 2022 Jun 13. Epub 2022 Jun 13.

Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan.

Background/aims: Very early-onset inflammatory bowel disease (VEO-IBD), defined as IBD diagnosed in patients younger than 6 years, is a challenge for pediatric gastroenterologists. Although there have been reports regarding VEO-IBD in Western countries, those in Asia are still lacking. This study aimed to investigate the clinical features of Japanese VEO-IBD patients. Read More

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Conditioning regimens for inborn errors of immunity: current perspectives and future strategies.

Int J Hematol 2022 Jul 8;116(1):7-15. Epub 2022 Jun 8.

Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Inborn errors of immunity (IEI) are caused by germline genetic mutations, resulting in defects of innate or acquired immunity. Hematopoietic cell transplantation (HCT) is indicated for curative therapy especially in patients with IEI who develop fatal opportunistic infections or severe manifestations of immune dysregulation. The first successful HCT for severe combined immunodeficiency (SCID) was reported in 1968. Read More

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Outcomes Following Treatment for Adenosine Deaminase Deficient Severe Combined Immunodeficiency: A Report from the PIDTC.

Blood 2022 Jun 7. Epub 2022 Jun 7.

Michigan State University College of Human Medicine, United States.

Adenosine deaminase (ADA) deficiency causes ~13% of cases of severe combined immune deficiency (SCID). Treatments include enzyme replacement therapy (ERT), hematopoietic cell transplant (HCT), and gene therapy (GT). We evaluated 131 ADA-SCID patients diagnosed between 1982-2017 who were enrolled in the Primary Immune Deficiency Treatment Consortium (PIDTC) SCID studies. Read More

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BCG Moreau Polish Substrain Infections in Patients With Inborn Errors of Immunity: 40 Years of Experience in the Department of Immunology, Children's Memorial Health Institute, Warsaw.

Front Pediatr 2022 19;10:839111. Epub 2022 May 19.

Department of Paediatrics, Rheumatology, Immunology and Metabolic Bone Diseases, Medical University of Bialystok, Bialystok, Poland.

Objective: We aimed to assess BCG (Bacillus Calmette-Guérin) complications in patients with Inborn Errors of Immunity (IEI), according to the inherited disorders and associated immunological defects, as well as the different BCG substrains.

Material: We studied adverse reactions to the locally-produced BCG Moreau vaccine, analyzed in patients with IEI diagnosed between 1980 and 2020 in the Department of Immunology, Children's Memorial Health Institute (CMHI), Warsaw. These results were compared with previously published studies. Read More

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Sirolimus Restores Erythropoiesis and Controls Immune Dysregulation in a Child With Cartilage-Hair Hypoplasia: A Case Report.

Front Immunol 2022 19;13:893000. Epub 2022 May 19.

Hematology Unit, Istituto di Ricerca e Cura a Carattere Scintifico (IRCCS) Istituto Giannina Gaslini, Genoa, Italy.

Cartilage-hair hypoplasia (CHH) is a syndromic immunodeficiency characterized by metaphyseal dysplasia, cancer predisposition, and varying degrees of anemia. It may present as severe combined immunodeficiency in infancy, or slowly progress until fully manifesting in late adolescence/adulthood. No targeted treatment is currently available, and patients are usually managed with supportive measures, or are offered a bone marrow transplant if the clinical phenotype is severe and a suitable donor is available. Read More

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In-utero exposure to immunosuppressive medications resulting in abnormal newborn screening for severe combined immunodeficiency: a case series on natural history and management.

Immunol Res 2022 Jun 3. Epub 2022 Jun 3.

Pediatric Allergy/Immunology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.

Exposure to immunosuppressive medication in utero is an important cause of secondary T cell lymphopenia in infancy, which can be detected via T cell receptor excision circle (TREC) quantification on severe combined immunodeficiency (SCID) newborn screening (NBS). At present, there is a paucity of literature surrounding management of these infants. A protocol including recommendations for vaccinations and follow-up is needed to augment care. Read More

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Development and evaluation of a novel xeno-free culture medium for human-induced pluripotent stem cells.

Stem Cell Res Ther 2022 Jun 3;13(1):223. Epub 2022 Jun 3.

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan.

Background: Human-induced pluripotent stem cells (hiPSCs) are considered an ideal resource for regenerative medicine because of their ease of access and infinite expansion ability. To satisfy the sizable requirement for clinical applications of hiPSCs, large-scale, expansion-oriented, xeno-free, and cost-effective media are critical. Although several xeno-free media for hiPSCs have been generated over the past decades, few of them are suitable for scalable expansion of cultured hiPSCs because of their modest potential for proliferation and high cost. Read More

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Cernunnos defect in an Iranian patient with T B NK severe combined immunodeficiency: A case report and review of the literature.

Mol Genet Genomic Med 2022 Jun 2:e1990. Epub 2022 Jun 2.

Immunology and Allergy Department, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Defective Cernunnos gene in nonhomologous end-joining (NHEJ) pathway of the DNA repair is responsible for radiosensitive severe combined immunodeficiency (SCID). Herein, presented a new patient with Cernunnos deficiency and summarized the clinical, immunological, and molecular features of reported patients in the literature.

Case: The patient was a 6-month-old female born to consanguineous parents. Read More

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Flow cytometry optimizing the diagnostic approach in inborn errors of immunity: experience from Egypt.

Allergy Asthma Clin Immunol 2022 Jun 2;18(1):45. Epub 2022 Jun 2.

Pediatric Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background: Human inborn errors of immunity (IEI) are a group of inherited genetic disorders of the immune system. IEI Patients suffer from severe repeated infections, autoimmunity, lymphadenopathy and/or increased susceptibility to malignancies. IEI are due to absence, disproportion, or loss of function of immune cells; mostly inherited in autosomal recessive manner, hence are more common in countries with high rate of consanguinity. Read More

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Introducing Newborn Screening for Severe Combined Immunodeficiency-The New Zealand Experience.

Int J Neonatal Screen 2022 May 10;8(2). Epub 2022 May 10.

Newborn Metabolic Screening Programme, LabPlus, Auckland District Health Board, Auckland 1148, New Zealand.

Screening for severe combined immunodeficiency (SCID) was added to the New Zealand national newborn screening programme in December 2017. Documentation pertaining to the application to add SCID to the panel and screening results over the first three years were reviewed. Screening evaluation metrics were shown to differ according to site of collection (babies in a neonatal intensive care unit vs. Read More

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Predictive value of CD8+ T cell and CD4/CD8 ratio at two years of successful ART in the risk of AIDS and non-AIDS events.

EBioMedicine 2022 Jun 26;80:104072. Epub 2022 May 26.

Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: While increased CD8 counts and low CD4/CD8 ratio during treated HIV correlate with immunosenescence, their additional predictive values to identify individuals with HIV at higher risk of clinical events remain controversial.

Methods: We selected treatment-naive individuals initiating ART from ACTG studies 384, 388, A5095, A5142, A5202, and A5257 who had achieved viral suppression at year 2. We examined the effect of CD8+ T cell counts and CD4/CD8 at year 2 on the probability of AIDS and serious non-AIDS events in years 3-7. Read More

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Respiratory syncytial virus infections requiring hospitalization in patients with primary immunodeficiency.

An Pediatr (Engl Ed) 2022 Jun 28;96(6):492-500. Epub 2022 May 28.

Grupo de Investigación de Infección en el Paciente Pediátrico Inmunodeprimido, Vall d'Hebron Institut de Recerca (VHIR); Unidad de Patología Infecciosa e Inmunodeficiencias de Pediatría, Hospital Universitari Vall d'Hebron; Centro Jeffrey Modell para Diagnóstico e Investigación en Inmunodeficiencias Primarias, Barcelona, Catalonia, Spain. Electronic address:

Introduction: The aim of the study was to assess the incidence of hospital admission due to severe acute respiratory infection by respiratory syncytial virus (RSV-ARI) in children with primary immunodeficiencies (PIDs) and the severity of RSV-ARI in these patients.

Methods: We conducted a nationwide cross-sectional retrospective and prospective multicentre study in the 2011-2017 period. The study was performed in 15 Spanish hospitals and included children with PID who required hospital admission due to RSV-ARI. Read More

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Prominent Follicular Keratosis in Multiple Intestinal Atresia with Combined Immune Deficiency Caused by a TTC7A Homozygous Mutation.

Genes (Basel) 2022 May 4;13(5). Epub 2022 May 4.

Dermatology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy.

Multiple intestinal atresia with combined immune deficiency (MIA-CID) is an autosomal recessive syndrome due to mutations in the TTC7A gene implicated in the polarization of intestinal and thymic epithelial cells. MIA-CID is lethal in the first year of life in the majority of patients. Dermatological manifestations have been reported in a few cases. Read More

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Oxidant-mediated modification and cross-linking of beta-2-microglobulin.

Free Radic Biol Med 2022 Jul 21;187:59-71. Epub 2022 May 21.

Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, 2200, Denmark. Electronic address:

Beta-2-microglobulin (B2M) is synthesized by all nucleated cells and forms part of the major histocompatibility complex (MHC) class-1 present on cell surfaces, which presents peptide fragments to cytotoxic CD8 T-lymphocytes, or by association with CD1, antigenic lipids to natural killer T-cells. Knockout of B2M results in loss of these functions and severe combined immunodeficiency. Plasma levels of this protein are low in healthy serum, but are elevated up to 50-fold in some pathologies including chronic kidney disease and multiple myeloma, where it has both diagnostic and prognostic value. Read More

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Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia.

Front Immunol 2022 6;13:864550. Epub 2022 May 6.

Department of Medicine, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, United States.

Nodular regenerative hyperplasia (NRH) is associated with high morbidity and mortality in patients with common variable immunodeficiency (CVID). While liver biopsy is the gold standard for NRH diagnosis, a non-invasive technique could facilitate early disease recognition, monitoring, and/or immune intervention. We performed a cross-sectional analysis of ultrasound-based transient elastography (TE) in patients with CVID to evaluate liver stiffness and compared this between patients with (N = 12) and without (N = 6) biopsy-proven NRH. Read More

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Combined Immunodeficiency Caused by a Novel De Novo Gain-of-Function RAC2 Mutation.

J Clin Immunol 2022 May 21. Epub 2022 May 21.

Department of Pediatric Research InstituteMinistry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and Disorders (Chongqing); China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.

Ras-related C3 botulinum toxin substrate 2 (RAC2) is a GTPase exclusively expressed in hematopoietic cells that acts as a pivotal regulator of several aspects of cell behavior via various cellular processes. RAC2 undergoes a tightly regulated GTP-binding/GTP-hydrolysis cycle, enabling it to function as a molecular switch. Mutations in RAC2 have been identified in 18 patients with different forms of primary immunodeficiency, ranging from phagocyte defects caused by dominant negative mutations to common variable immunodeficiency resulting from autosomal recessive loss-of-function mutations, or severe combined immunodeficiency due to dominant activating gain-of-function mutations. Read More

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Dysmorphism and immunodeficiency - One of the differential diagnoses is PAX1 related otofaciocervical syndrome type 2.

Eur J Med Genet 2022 Jul 17;65(7):104523. Epub 2022 May 17.

Department of Clinical Genetics, Birmingham Women's and Children's Hospital, UK.

Otofaciocervical syndrome (OTFCS) is a rare condition associated with short stature, abnormal facial features and conductive hearing loss. OTFCS type 2 (OTFCS) is an autosomal recessive form of this condition with associated T cell deficiency due to biallelic variants in PAX1. We report a female child born to a consanguineous couple with homozygous PAX1 variant. Read More

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Deficiency of Human Adenosine Deaminase Type 2 - A Diagnostic Conundrum for the Hematologist.

Front Immunol 2022 3;13:869570. Epub 2022 May 3.

Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Deficiency of adenosine deaminase type 2 (DADA2) was first described in 2014 as a monogenic cause of polyartertitis nodosa (PAN), early onset lacunar stroke and livedo reticularis. The clinical phenotype of DADA2 is, however, very broad and may involve several organ systems. Apart from vasculitis, children may present with i) Hematological manifestations (ii) Lymphoproliferation and iii) Immunodeficiencies. Read More

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Coxiella burnetii Plasmid Effector B Promotes LC3-II Accumulation and Contributes To Bacterial Virulence in a SCID Mouse Model.

Infect Immun 2022 Jun 19;90(6):e0001622. Epub 2022 May 19.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Fengtai, Beijing, People's Republic of China.

Coxiella burnetii, the causative agent of zoonotic Q fever, is characterized by replicating inside the lysosome-derived -containing vacuole (CCV) in host cells. Some effector proteins secreted by C. burnetii have been reported to be involved in the manipulation of autophagy to facilitate the development of CCVs and bacterial replication. Read More

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Direct bone marrow injection of human bone marrow-derived stromal cells into mouse femurs results in greater prostate cancer PC-3 cell proliferation, but not specifically proliferation within the injected femurs.

BMC Cancer 2022 May 17;22(1):554. Epub 2022 May 17.

School of Biomedical Science, Faculty of Health, Queensland University of Technology at the Translational Research Institute, Brisbane, Australia.

Background: While prostate cancer (PCa) cells most often metastasize to bone in men, species-specific differences between human and mouse bone marrow mean that this pattern is not faithfully replicated in mice. Herein we evaluated the impact of partially humanizing mouse bone marrow with human bone marrow-derived stromal cells (BMSC, also known as "mesenchymal stem cells") on human PCa cell behaviour.

Methods: BMSC are key cellular constituents of marrow. Read More

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Clinical Dose Preparation of [Lu]Lu-DOTA-Pertuzumab Using Medium Specific Activity [Lu]LuCl for Radioimmunotherapy of Breast and Epithelial Ovarian Cancers, with HER2 Receptor Overexpression.

Cancer Biother Radiopharm 2022 Jun 16;37(5):384-402. Epub 2022 May 16.

Homi Bhabha National Institute, Mumbai, India.

The overexpression of human epidermal growth factor receptor 2 (HER2) is commonly associated with metastatic breast cancer and epithelial ovarian cancer. The U.S. Read More

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signaling in the regulation of rheumatoid synovial aggression.

Ann Transl Med 2022 Apr;10(8):431

Department of Rheumatology and Immunology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Fibroblast-like synoviocytes (FLSs) play a critical role in promoting synovial aggression and joint destruction in rheumatoid arthritis (RA). Cyclic GMP-AMP synthase ()/stimulator of interferon gene () signaling plays an important role in controlling a series of cellular biological processes. However, it is still unclear whether signaling regulates rheumatoid synovial aggression. Read More

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Synergistic efficacy of homoharringtonine and venetoclax on acute myeloid leukemia cells and the underlying mechanisms.

Ann Transl Med 2022 Apr;10(8):490

Department of Hematopathy, Henan Institute of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.

Background: To evaluate whether homoharringtonine (HHT) combined with venetoclax could produce a synergistic anti-acute myeloid leukemia (AML) effect and determine the underlying mechanisms.

Methods: The effect of HHT and venetoclax combination on cell viability, apoptosis, and mitochondrial membrane potential was investigated using AML cell lines and primary cells. High-throughput mRNA sequencing was used to analyze mRNA level changes after the application of HHT and venetoclax on OCI-AML3 cells. Read More

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Lentiviral Mediated Gene Transfer Corrects the Defects Associated With Deficiency of Adenosine Deaminase Type 2.

Front Immunol 2022 22;13:852830. Epub 2022 Apr 22.

Infection, Immunity, Inflammation Department, University College London (UCL) Great Ormond Street Institute of Child Health, London, United Kingdom.

Deficiency of adenosine deaminase type 2 (DADA2) is an autosomal recessive disease caused by bi-allelic loss-of-function mutations in . Treatment with anti-TNF is effective for the autoinflammatory and vasculitic components of the disease but does not correct marrow failure or immunodeficiency; and anti-drug antibodies cause loss of efficacy over time. Allogeneic haematopoietic stem cell transplantation may be curative, but graft versus host disease remains a significant concern. Read More

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Inborn Errors of Immunity in Algerian Children and Adults: A Single-Center Experience Over a Period of 13 Years (2008-2021).

Front Immunol 2022 21;13:900091. Epub 2022 Apr 21.

Department of Children's Infectious Diseases, Canastel Children's Hospital, University of Oran, Oran, Algeria.

Background: Inborn errors of immunity (IEI) predispose patients to various infectious and non-infectious complications. Thanks to the development and expanding use of flow cytometry and increased awareness, the diagnostic rate of IEI has markedly increased in Algeria the last decade.

Aim: This study aimed to describe a large cohort of Algerian patients with probable IEI and to determine their clinical characteristics and outcomes. Read More

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Scales of Magt1 Gene: Novel Mutations, Different Presentations.

Iran J Allergy Asthma Immunol 2022 Feb 6;21(1):92-97. Epub 2022 Feb 6.

Department of Pediatric, Immunology and Allergy and Hematopoietic Stem Cell Transplantation Unit, School of Medicine, Ankara University, Ankara, Turkey.

Loss-of-function mutations in magnesium transporter 1 (MAGT1) gene cause X-linked magnesium deficiency with Epstein-Barr virus (EBV) infection and neoplasm (X-MEN), a disease with quite diverse clinical and immunological consequences. The phenotypic characteristics of the initially described patients included CD4+ T cell lymphopenia, immune deficiency, EBV viremia, and EBV-related lymphoproliferative disease. To date, a total of 25 patients have been reported. Read More

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February 2022