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Eur J Neurol 2020 Jul 9. Epub 2020 Jul 9.

Department of Neurology, Ruprecht-Karls-Universität Heidelberg Medizinische Fakultät Mannheim, Mannheim, Germany.

Progressive multifocal leukoencephalopathy (PML) is a rare but severe opportunistic CNS infection caused by JC polyomavirus in immunosuppressed patients. Immune checkpoint blockade stimulates immune function and has been suggested to reinvigorate viral clearance in PML patients by expanding JCV-specific T cells . Among the first 13 published PML patients treated with programmed cell death 1 inhibitors (PD1I) 8 showed a mild to marked treatment response . Read More

Expert Rev Clin Immunol 2020 Jul 7. Epub 2020 Jul 7.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences , Tehran, Iran.

Objectives: Human Ficolin-3 () is an oligomeric-structured lectin encoded by the gene with a pivotal role in the lectin complement pathway. It has anti-microbial activities against bacterial and viral infections and restrains opportunistic pathogens. Mutation in the gene is associated with variable clinical manifestations particularly immunologic (infections and autoimmunity) and neurologic complications. Read More

Clin Immunol 2020 Jul 3:108520. Epub 2020 Jul 3.

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Severe Combined Immunodeficiency (SCID) is a genetically heterogeneous group of disorders characterized by severe T cell lymphopenia and defective T and B cell function. Without prompt diagnosis and early intervention, patients with SCID typically die from infection within the first year of life. Advances in molecular genetics have led to rapid and efficient diagnosis of SCID cases, particularly when paired with newborn screening. Read More

Prostate 2020 Jul 6. Epub 2020 Jul 6.

Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.

Background: Although androgen deprivation therapy (ADT) is the initial treatment strategy for prostate cancer (PCa), recurrent castration-resistant prostate cancer (CRPC) eventually ensues. In this study, cancer-derived immunoglobulin G (CIgG) is found to be induced after ADT, identifying CIgG as a potential CRPC driver gene.

Methods: The expression of CIgG and its clinical significance in PCa tissue was analyzed by The Cancer Genome Atlas database and immunohistochemistry. Read More

Viruses 2020 Jun 23;12(6). Epub 2020 Jun 23.

Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC 27607, USA.

Cutaneous papillomaviruses can cause severe, persistent infections and skin cancer in immunodeficient patients, including people with X-linked severe combined immunodeficiency (XSCID). A similar phenotype is observed in a canine model of XSCID; these dogs acquire severe cutaneous papillomavirus infections that can progress to cancer in association with canine papillomavirus type 2 (CPV2). This canine model system provides a natural spontaneous animal model for investigation of papillomavirus infections in immunodeficient patients. Read More

Front Immunol 2020 2;11:925. Epub 2020 Jun 2.

Department of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff, Bad Nauheim, Germany.

The long-distance migration of rheumatoid arthritis synovial fibroblasts (RASFs) in the severe combined immunodeficiency (SCID) mouse model of rheumatoid arthritis (RA) suggests that an interaction between RASFs and endothelial cells (EC) is critical in this process. Our objective was to assess whether immunomodulatory factors such as adipokines and antirheumatic drugs affect the adhesion of RASFs to ECs or the expression of surface molecules. Primary ECs or human umbilical vein endothelial cell (HUVEC) and primary RASFs were stimulated with adiponectin (10 μg/mL), visfatin (100 ng/mL), and resistin (20 ng/mL) or treated with methotrexate (1. Read More

Swiss Med Wkly 2020 Jun 24;150:w20254. Epub 2020 Jun 24.

University Children's Hospital Zurich, Switzerland.

The recent introduction of newborn screening for severe primary T and B cell deficiencies in Switzerland allows rapid identification of patients with severe combined immunodeficiency (SCID). Outcomes for SCID are greatly improved by early diagnosis and treatment with allogeneic haematopoietic stem cell transplantation or, in selected cases, gene therapy. National centralised newborn screening is performed in Switzerland since January 2019 using a combined T cell receptor excision circles (TREC) / κ-deleting recombination excision circles (KREC) assay, also revealing infants with non-SCID severe T and B cell disorders, who are often diagnosed with a substantial delay. Read More

Proc Natl Acad Sci U S A 2020 Jul 22;117(27):15673-15683. Epub 2020 Jun 22.

Department of Microbiology, Tumor and Cell Biology, Biomedicum, Karolinska Institutet, SE-171 65, Stockholm, Sweden;

Stemness encompasses the capability of a cell for self-renewal and differentiation. The stem cell maintains a balance between proliferation, quiescence, and regeneration via interactions with the microenvironment. Previously, we showed that ectopic expression of the mitochondrial ribosomal protein S18-2 (MRPS18-2) led to immortalization of primary fibroblasts, accompanied by induction of an embryonic stem cell (ESC) phenotype. Read More

Indian Pediatr 2020 Jun;57(6):571-572

Department of Paediatric Surgery, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.

Sci Rep 2020 Jun 19;10(1):9957. Epub 2020 Jun 19.

Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.

Severe immunodeficient mice are widely used to examine human and animal cells behaviour in vivo. However, mice are short-lived and small in size; while large animals require specific large-scale equipment. Rabbits are also commonly employed as experimental models and are larger than mice or rats, easy to handle, and suitable for long-term observational and pre-clinical studies. Read More

J Allergy Clin Immunol 2020 Jun 16. Epub 2020 Jun 16.

University College London Great Ormond Street Institute of Child Health, and Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. Electronic address:

J Autoimmun 2020 Apr 10:102462. Epub 2020 Apr 10.

Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Hospital, Jerusalem, 91120, Israel. Electronic address:

Nodding Syndrome (NS) is a fatal pediatric epilepsy of unknown etiology, accompanied by multiple neurological impairments, and associated with Onchocerca volvulus (Ov), malnutrition, war-induced trauma, and other insults. NS patients have neuroinflammation, and ~50% have cross-reactive Ov/Leiomodin-1 neurotoxic autoimmune antibodies. RESULTS: Studying 30 South Sudanese NS patients and a similar number of healthy subjects from the same geographical region, revealed autoimmune antibodies to 3 extracellular peptides of ionotropic glutamate receptors in NS patients: AMPA-GluR3B peptide antibodies (86%), NMDA-NR1 peptide antibodies (77%) and NMDA-NR2 peptide antibodies (87%) (in either 1:10, 1:100 or 1:1000 serum dilution). Read More

Turk J Pediatr 2020 ;62(3):379-386

Division of Pediatric Allergy and Immunology, Department of Pediatrics, Marmara University Faculty of Medicine, İstanbul, Turkey.

Background And Objective: Adverse reactions related to intravenous immunoglobulin (IVIG) infusions vary from 1 to 81%, with an average of 20%. They may be classified as immediate; occurring during the infusion itself or delayed; occurring after the infusion has been ceased. In the present study, we aimed to evaluate the frequency of immediate adverse reactions due to IVIG infusions in primary immune deficiency (PID) patients. Read More

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Jun;28(3):1025-1031

Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorder; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics,Department of Hematology and Oncology, Children's Hospital of Chongqing Medical University; Chongqing, 400014, China,Email:

Objective: To investigate the prevalence of respiratory viral infections in patients with primary immunodeficiency disease (PID) during hematopoietic stem cell transplantation.

Methods: 108 specimens of nasopharyngeal aspirate were collected from 22 PID patients before and after hematopoietic stem cell transplantation from July 2016 to July 2018 in the Department of Hematology. The TR-PCR was used to detect for respiratory viruses including respiratory syncytial virus(RSV)，human metapneumoviros(hMPV)，coronavirus(CoV) and parainfluenza 1-3 (PIV1-3). Read More

Contemp Clin Trials Commun 2020 Sep 29;19:100575. Epub 2020 May 29.

Department of Pneumology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.

Introduction: Sarcoidosis is a granulomatous systemic disease that becomes chronic in approximately one third of affected patients resulting in quality of life and functional impairment. Immunosuppressive drugs other than steroids represent alternative therapeutic options, but side effects like liver and bone marrow toxicity or increased susceptibility to infections limit their use. Pathophysiological studies in sarcoidosis patients demonstrate altered regulatory T-cell functions with a reduced expression of CTLA-4 (CD152) and prolonged inflammation. Read More

Hum Biol 2020 Jul;91(3):189-208

Division of Biomedical Informatics and Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA,

To date, some genetic studies offer medical benefits but lack a clear pathway to benefit for people from underrepresented backgrounds. Historically, Indigenous people, including the Diné (Navajo people), have raised concerns about the lack of benefits, misuse of DNA samples, lack of consultation, and ignoring of cultural and traditional ways of knowing. Shortly after the Navajo Nation Human Research Review Board was established in 1996, the Navajo Nation recognized growing concerns about genetic research, and in 2002 they established a moratorium on human genetic research studies. Read More

Pharmaceutics 2020 Jun 13;12(6). Epub 2020 Jun 13.

Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.

Recent clinical trials using patient's own corrected hematopoietic stem cells (HSCs), such as for primary immunodeficiencies (Adenosine deaminase (ADA) deficiency, X-linked Severe Combined Immunodeficiency (SCID), X-linked chronic granulomatous disease (CGD), Wiskott-Aldrich Syndrome (WAS)), have yielded promising results in the clinic; endorsing gene therapy to become standard therapy for a number of diseases. However, the journey to achieve such a successful therapy is not easy, and several challenges have to be overcome. In this review, we will address several different challenges in the development of gene therapy for immune deficiencies using our own experience with Recombinase-activating gene 1 (RAG1) SCID as an example. Read More

J Leukoc Biol 2020 Jun 15. Epub 2020 Jun 15.

Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The dedicator of cytokinesis (DOCK) family proteins consist of 11 members, each of which contains 2 domains, DOCK homology region (DHR)-1 and DHR-2, and as guanine nucleotide exchange factors, they mediate activation of small GTPases. Both DOCK2 and DOCK8 deficiencies in humans can cause severe combined immunodeficiency, but they have different characteristics. DOCK8 defect mainly causes high IgE, allergic disease, refractory skin virus infection, and increased incidence of malignant tumor, whereas DOCK2 defect mainly causes early-onset, invasive infection with less atopy and increased IgE. Read More

Cureus 2020 May 13;12(5):e8089. Epub 2020 May 13.

Neurological Surgery, Miami Cancer Institute, Baptist Health South Florida, Miami, USA.

Intracranial hypotension (IH) is a relatively common condition associated with low cerebrospinal (CSF) pressure. The most typical symptom is orthostatic headache, although neurological deficits and changes in the level of consciousness, such as encephalopathy, stupor, and coma, may also occur. Uncomplicated CSF hypotension headaches generally resolve with rest, hydration, and analgesia. Read More

Medicine (Baltimore) 2020 Jun;99(24):e20505

Department of Hematology Oncology.

Introduction: X-linked hyper-IgM syndrome is a type of primary combined immunodeficiency disorder caused by mutations in CD40 ligand. Opportunistic infections caused by P jirovecii, cytomegalovirus (CMV), or fungi are frequently the first presenting symptom of the patients with X-linked hyper-IgM syndrome.

Patient Concerns: Here, we report a 10-month-old infant who presented with cyanosis and shortness of breath. Read More

Eur J Med Genet 2020 Jun 12;63(9):103974. Epub 2020 Jun 12.

Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK. Electronic address:

Ligase IV (LIG4) syndrome is a rare disorder of DNA damage repair caused by biallelic, pathogenic variants in LIG4. This is a phenotypically heterogeneous condition with clinical presentation varying from lymphoreticular malignancies in developmentally normal individuals to significant microcephaly, primordial dwarfism, radiation hypersensitivity, severe combined immunodeficiency and early mortality. Renal defects have only rarely been described as part of the ligase IV disease spectrum. Read More

Cold Spring Harb Mol Case Stud 2020 Jun 12;6(3). Epub 2020 Jun 12.

MSK Kids, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.

Reticular dysgenesis is a form of severe combined immunodeficiency (SCID) caused by biallelic pathogenic variants in Here we present the case of a boy diagnosed with SCID following a positive newborn screen (NBS). Genetic testing revealed a homozygous variant: c.330 + 5G > A. Read More

Immunobiology 2020 May 20;225(3):151961. Epub 2020 May 20.

Department of Medical Genetics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background And Objective: Severe combined immunodeficiency disease (SCID) is a rare inherited severe immunodeficiency, in which functions of T cells and B cells are impaired. SCID is inherited either in X-linked recessive, or autosomal recessive forms, and is either radiosensitive or radioresistant. Artemis (DCLRE1C gene), DNA ligase IV, DNA-PKC, and Cernunnos/XLF proteins are regarded as NHEJ (Non-Homologous End-Joining) proteins that are involved in the repair process of double-strand DNA breaks and their mutations would lead to cellular radiosensitivity. Read More

J Clin Immunol 2020 Jun 8. Epub 2020 Jun 8.

College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

Background: Purine nucleoside phosphorylase (PNP) deficiency accounts for about 4% of severe combined immunodeficiency diseases. PNP deficiency is a variable disease with recurrent infections and neurodevelopmental delay. Autoimmunity and malignancy can still occur in one-third of patients. Read More

Scand J Immunol 2020 Jun 7:e12913. Epub 2020 Jun 7.

Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Cartilage-hair hypoplasia (CHH) is an autosomal recessive syndromic immunodeficiency with skeletal dysplasia, short stature, hypotrichosis, variable degree of immune dysfunction and increased incidence of anaemia, Hirschsprung disease and malignancy. CHH is caused by variants in the RMRP gene, encoding the untranslated RNA molecule of the mitochondrial RNA-processing endoribonuclease, which participates in for example cell cycle regulation and telomere maintenance. Recent studies have expanded our understanding of the complex pathogenesis of CHH. Read More

Neurol Neuroimmunol Neuroinflamm 2020 Jul 4;7(4). Epub 2020 Jun 4.

From the Department of Neurology (X.A., C.C.-D., P.L.), Montpellier University Hospital, INSERM, Univ Montpellier, Montpellier; Internal Medicine Department (R.G.), Caremeau University Hospital, Nimes; Department of Paediatrics (E.J.), Montpellier University Hospital, INSERM, Univ Montpellier; Médecine interne multi-organes (P.R., P.G.), Montpellier University Hospital, INSERM, Univ Montpellier; Department of Immunology (C.L., P.P., T.V.), Montpellier University Hospital, INSERM, Univ Montpellier; Internal Medicine Department (J.F.V.), Bordeaux University Hospital, Univ Bordeaux; Department of Neuroradiology (N.M.C.), Montpellier University Hospital, INSERM, Univ Montpellier; Université de Paris (F.R.-L., C.B.), Imagine institute, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Paris; and Laboratory of Molecular Genetics (M.K., C.G.), Montpellier University Hospital, INSERM, Univ Montpellier, France.

Objective: To describe the clinical and radiologic neurologic characteristics of patients with cytotoxic T-lymphocyte antigen-4 () haploinsufficiency.

Methods: Three patients from 2 families had neurologic manifestations in the context of haploinsufficiency. Their clinical and MRI findings are presented. Read More

Int J Infect Dis 2020 Jun 2;97:117-125. Epub 2020 Jun 2.

Infectious Disease Service, Department of Pediatric Medicine, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore 117597, Singapore; Duke-National University of Singapore Medical School, 8 College Road, Singapore 169857, Singapore; Lee Kong Chian School of Medicine, National Technological University, 59 Nanyang Drive, Experimental Medicine Building, Singapore 636921, Singapore.

Background: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs).

Methods: A 15-year retrospective review was conducted in KK Women's and Children's Hospital in Singapore, from January 2003 to October 2017.

Results: Ten patients were identified, the majority male (60. Read More

J Investig Allergol Clin Immunol 2020 Jun 3. Epub 2020 Jun 3.

Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.

Br J Clin Pharmacol 2020 May 29. Epub 2020 May 29.

Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland.

Aims: The impact of ageing on antiretroviral pharmacokinetics remains uncertain, leading to missing dosing recommendations for elderly people living with human immunodeficiency virus (HIV: PLWH). The objective of this study was to investigate whether ageing leads to clinically relevant pharmacokinetic changes of antiretrovirals that would support a dose adjustment based on the age of the treated PLWH.

Methods: Plasma concentrations for 10 first-line antiretrovirals were obtained in PLWH ≥55 years, participating in the Swiss HIV Cohort Study, and used to proof the predictive performance of our physiologically based pharmacokinetic (PBPK) model. Read More

J Clin Immunol 2020 May 26. Epub 2020 May 26.

Department of Paediatrics, Helios Klinikum Krefeld, Krefeld, Germany.

Purpose: Severe combined immunodeficiencies (SCID) are a heterogeneous group of fatal genetic disorders, in which the immune response is severely impaired. SCID can be cured if diagnosed early. We aim to determine the incidence of clinically defined SCID cases, acquire data of reported cases and evaluate their possible prediction by newborn screening, before introduction of a general screening program in Germany. Read More

J Clin Immunol 2020 May 26. Epub 2020 May 26.

Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, DIR, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.

"X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia" (XMEN) disease is an inborn error of glycosylation and immunity caused by loss of function mutations in the magnesium transporter 1 (MAGT1) gene. It is a multisystem disease that strongly affects certain immune cells. MAGT1 is now confirmed as a non-catalytic subunit of the oligosaccharyltransferase complex and facilitates Asparagine (N)-linked glycosylation of specific substrates, making XMEN a congenital disorder of glycosylation manifesting as a combined immune deficiency. Read More

Int J Immunogenet 2020 May 22. Epub 2020 May 22.

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

Severe combined immunodeficiency (SCID) has a diverse genetic aetiology, where a clinical phenotype, caused by single and/or multiple gene variants, can give rise to multiple presentations. The advent of next-generation sequencing (NGS) has recently enabled rapid identification of the molecular aetiology of SCID, which is crucial for prognosis and treatment strategies. We sought to identify the genetic aetiology of various phenotypes of SCIDs and assessed both clinical and immunologic characteristics associated with gene variants. Read More

Clin Genet 2020 May 22. Epub 2020 May 22.

Department of Medical Genetics, St. Petersburg State Pediatric Medical University, St. Petersburg, Russia.

Primary immune deficiencies are usually attributed to genetic defects and, therefore, frequently referred to as inborn errors of immunity (IEI). We subjected the genomic DNA of 333 patients with clinical signs of IEI to next generation sequencing (NGS) analysis of 344 immunity-related genes and, in some instances, additional genetic techniques. Genetic causes of the disease were identified in 69/333 (21%) of subjects, including 11/18 (61%) of children with syndrome-associated IEIs, 45/202 (22%) of nonsyndromic patients with Jeffrey Modell Foundation (JMF) warning signs, 9/56 (16%) of subjects with periodic fever, 3/30 (10%) of cases of autoimmune cytopenia, 1/21 (5%) of patients with unusually severe infections and 0/6 (0%) of individuals with isolated elevation of IgE level. Read More

Joint Bone Spine 2020 May 11. Epub 2020 May 11.

University Claude-Bernard Lyon 1, 69007 Lyon, France; Department of rheumatology, Lyon Sud hospital, hospices civils de Lyon, Pierre-Bénite, France; Inserm UMR1033, Lyon, France. Electronic address:

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare monogenic primary immunodeficiency due to mutations of FOXP3, a master transcription factor of regulatory T cells (Treg). IPEX syndrome leads to fatal course in most cases during early childhood or severe multi-organ immune-mediated disorders in patients who survive. Currently hematopoietic stem cell transplantation represents the only known effective cure for IPEX syndrome. Read More

Front Immunol 2020 6;11:885. Epub 2020 May 6.

Immune Deficiency Foundation Towson, Towson, MD, United States.

Now that severe combined immune deficiency (SCID) has been added to newborn screening panels in all 50 states in the U.S., there is a need to develop and disseminate well-designed educational materials to parents who need information to make informed decisions about treatment and care for identified infants. Read More

J Craniofac Surg 2020 Jun;31(4):e426-e428

Department of Plastic and Reconstructive Surgery and Burn Unit, Centro Hospitalar de São João, Porto Medical School, Alameda Professor Hernâni Monteiro, Porto, Portugal.

There are patients with craniofacial deformity that can lead to extensive bone loss and severe disfigurement. Autologous reconstruction may be challenging in these patients, and it is usually associated with flap donor area morbidity and unfavorable aesthetic and functional results. A 51-year-old patient with human immunodeficiency virus infection, developed in the context of immunosuppression a fulminant fungal rhino-sinusitis with the need for surgical debridement, and in consequence extensive destruction of the nasal cavity and upper jaw, resulting in severe disfigurement due to nasal deformity and maxillary collapse. Read More

Reprod Sci 2020 Aug;27(8):1609-1619

IVI Foundation, Av. Fernando Abril Martorell, 106-TorreA-Plantal, 46026, 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

Mol Genet Metab 2020 Jul 5;130(3):179-182. Epub 2020 May 5.

Department of Human Genetics, McGill University, Montreal, Quebec, Canada.; Division of Medical Genetics, Department of Specialized Medicine, McGill University Health Centre, Montreal, Quebec, Canada.; Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.; Division of Medical Biochemistry, Department of Specialized Medicine, McGill University Health Centre, Montreal, Quebec, Canada.

MTHFD1 is a trifunctional protein containing 10-formyltetrahydrofolate synthetase, 5,10-methenyltetrahydrofolate cyclohydrolase and 5,10-methylenetetrahydrofolate dehydrogenase activities. It is encoded by MTHFD1 and functions in the cytoplasmic folate cycle where it is involved in de novo purine synthesis, synthesis of thymidylate and remethylation of homocysteine to methionine. Since the first reported case of severe combined immunodeficiency resulting from MTHFD1 mutations, seven additional patients ascertained through molecular analysis have been reported with variable phenotypes, including megaloblastic anemia, atypical hemolytic uremic syndrome, hyperhomocysteinemia, microangiopathy, infections and autoimmune diseases. Read More

PLoS One 2020 15;15(5):e0233016. Epub 2020 May 15.

Department of Pediatric Surgery, University Hospital of Freiburg, Freiburg, Germany.

Tunneled central venous catheters (TCVCs) provide prolonged intravenous access for pediatric patients with severe primary immunodeficiency disease (PID) undergoing hematopoietic stem cell transplantation (HSCT). However, little is known about the epidemiology and clinical significance of TCVC-related morbidity in this particular patient group. We conducted the retrospective analysis of patients with severe PID who received percutaneous landmark-guided TCVC implantation prior to HSCT. Read More

Curr Opin Clin Nutr Metab Care 2020 Jul;23(4):241-246

Department of Human Genetics, McGill University.

Purpose Of Review: Immune dysfunction, including severe combined immunodeficiency, has been described in genetic disorders affecting the metabolism of the vitamins cobalamin (vitamin B12) and folate. We have reviewed reports of clinical findings in patients with a number of inborn errors of cobalamin or folate metabolism, specifically looking for immune problems.

Recent Findings: There is little evidence that immune function is affected in most of the disorders. Read More

Allergol Immunopathol (Madr) 2020 May 11. Epub 2020 May 11.

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Educationan and Research Netwrork (USERN), Tehran, Iran. Electronic address:

Introduction: The prevalence of undiagnosed primary immunodeficiency diseases is remarkably high and contributes to increasing the rate of morbidity and mortality among this group of patients.

Objective: To examine the 10 warning sign scoring system in patients suspected of primary immune deficiency and also estimate the diagnostic delay in patients with proven disease.

Methods: This descriptive cross-sectional study was carried out during the years 2015-2016 in Ali Asghar (AS) Clinic and Hospital. Read More

J Leukoc Biol 2020 May 11. Epub 2020 May 11.

Unit of Immune and Infectious Diseases, Academic Department of Pediatrics, Bambino Gesù Childrens' Hospital-Scientific Institute for Research and Healthcare (IRCCS), Rome, Italy.

X-linked severe combined immunodeficiency (X-SCID) caused by full mutation of the IL2RG gene leads to T B NK phenotype and is usually associated with severe opportunistic infections, diarrhea, and failure to thrive. When IL2RG hypomorphic mutation occurs, diagnosis could be delayed and challenging since only moderate reduction of T and NK cells may be present. Here, we explored phenotypic insights and the impact of the p. Read More

J Allergy Clin Immunol 2020 May 6. Epub 2020 May 6.

Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address:

Background: Mutations in the recombinase-activating genes cause severe immunodeficiency, with a spectrum of phenotypes ranging from severe combined immunodeficiency to immune dysregulation. Hematopoietic stem cell transplantation is the only curative option, but a high risk of graft failure and poor immune reconstitution have been observed in the absence of myeloablation.

Objectives: Our aim was to improve multilineage engraftment; we tested nongenotoxic conditioning with anti-CD45 mAbs conjugated with saporin CD45 (CD45-SAP). Read More

Blood 2020 Jun;135(25):2302-2315

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.

Erythropoiesis is a complex multistage process that involves differentiation of early erythroid progenitors to enucleated mature red blood cells, in which lineage-specific transcription factors play essential roles. Erythroid Krüppel-like factor (EKLF/KLF1) is a pleiotropic erythroid transcription factor that is required for the proper maturation of the erythroid cells, whose expression and activation are tightly controlled in a temporal and differentiation stage-specific manner. Here, we uncover a novel role of G-protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor/silencing mediator of retinoic acid and thyroid hormone receptor corepressor complex, in erythrocyte differentiation. Read More

J Clin Immunol 2020 May 6;40(4):625-636. Epub 2020 May 6.

Department of Immunology, Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, 1, Samory Mashela str., Moscow, Russia, 117997.

Introduction: The live-attenuated BCG vaccine is known to cause disseminated Mycobacterium bovis infection in patients with severe combined immunodeficiency (SCID). However, BCG-related post-hematopoietic stem cell transplantation (HSCT) immune reconstitution inflammatory syndromes, similar to those described in patients with HIV infections, are less-known complications of SCID.

Patients And Methods: We reported on 22 BCG-vaccinated SCID patients who had received conditioned allogeneic HSCT with TCRαβ+/CD19+ graft depletion. Read More

Eur Ann Allergy Clin Immunol 2020 May 6. Epub 2020 May 6.

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

Summary: Primary Immunodeficiency diseases(PID) are common in patients with non-cystic fibrosis bronchiectasis(NCFB). Our objective was to determine ratio/types of PID in NCFB. Seventy NCFB patients followed up in a two-year period were enrolled. Read More

Clin Immunol 2020 Jun 30;215:108453. Epub 2020 Apr 30.

Medical Genetics Unit, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon; Department of Medical Genetics, Hotel Dieu de France, Beirut, Lebanon.

Immunodeficiency, Centromeric instability and Facial anomalies (ICF) syndrome is a group of rare autosomal recessive disorders. The immune disease in the ICF syndrome consists mainly of humoral immunodeficiency. T-cell dysfunction has previously been suspected to be part of the syndrome's spectrum. Read More

Gene Ther 2020 Apr 27. Epub 2020 Apr 27.

Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.

Autologous gene therapy using lentiviral vectors (LVs) holds promise for treating monogenetic blood diseases. However, clinical applications can be limited by suboptimal hematopoietic stem cell (HSC) transduction and insufficient quantities of available vector. We recently reported gene therapy for X-linked severe combined immunodeficiency using a protocol in which patient CD34 cells were incubated with two successive transductions. Read More

BMC Infect Dis 2020 Apr 25;20(1):309. Epub 2020 Apr 25.

Baylor College of Medicine, 1 Baylor Plaza BCM 620, Houston, TX, 77030-3411, USA.

Background: Clinical manifestations of extraneural infection with the pork tapeworm Taenia solium typically affect the muscles, eyes, alimentary canal, and/or subcutaneous tissues. Children living with HIV are at increased risk for more widespread and severe manifestations of food-borne opportunistic infections, including T. solium, due to fluctuating levels of immunosuppression. Read More

Cancers (Basel) 2020 Apr 22;12(4). Epub 2020 Apr 22.

Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.

Immune checkpoint blockade (ICB) monotherapy shows early promise for the treatment of nasopharyngeal carcinoma (NPC) in patients. Nevertheless, limited representative NPC models hamper preclinical studies to evaluate the efficacy of novel ICB and combination regimens. In the present study, we engrafted NPC biopsies in non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain-null (NSG) mice and established humanized mouse NPC-patient-derived xenograft (NPC-PDX) model successfully. Read More