1,433 results match your criteria autoimmunity genetically

Definitive evidence for Club cells as progenitors for mutant Kras/Trp53-deficient lung cancer.

Int J Cancer 2021 Jul 31. Epub 2021 Jul 31.

Institute of Translational Immunology (TIM), University Medical Center, Johannes Gutenberg-University, Mainz, Germany.

Accumulating evidence suggests that both the nature of oncogenic lesions and the cell-of-origin can strongly influence cancer histopathology, tumor aggressiveness and response to therapy. However and although oncogenic Kras expression and loss of Trp53 tumor suppressor gene function have been demonstrated to initiate murine lung adenocarcinomas (LUADs) in alveolar type II (AT2) cells, clear evidence that Club cells, representing the second major subset of lung epithelial cells, can also act as cells-of-origin for LUAD is lacking. Equally, the exact anatomic location of Club cells that are susceptible to Kras transformation and the resulting tumor histotype remain to be established. Read More

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Characteristics of children diagnosed with type 1 diabetes before vs after 6 years of age in the TEDDY cohort study.

Diabetologia 2021 Jul 22. Epub 2021 Jul 22.

National Institute of Diabetes & Digestive & Kidney Diseases, Bethesda, MD, USA.

Aims/hypothesis: Prognostic factors and characteristics of children diagnosed with type 1 diabetes before 6 years of age were compared with those diagnosed at 6-13 years of age in the TEDDY study.

Methods: Genetically high-risk children (n = 8502) were followed from birth for a median of 9.9 years; 328 (3. Read More

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Molecular regulation and dysregulation of T follicular helper cells - learning from inborn errors of immunity.

Curr Opin Immunol 2021 Jul 17;72:249-261. Epub 2021 Jul 17.

Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine & Health, UNSW Sydney, Darlinghurst, NSW 2010 Australia; CIRCA (Clinical Immunogenomics Consortium of Australasia), Australia.

The production of high-affinity antibodies is a key feature of the vertebrate immune system. Antibodies neutralize and clear pathogens, thereby protecting against infectious diseases. However, dysregulated production of antibodies can cause immune pathologies, such as autoimmunity and immune deficiency. Read More

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Increased burden of rare variants in genes of the endosomal Toll-like receptor pathway in patients with systemic lupus erythematosus.

Lupus 2021 Jul 16:9612033211033979. Epub 2021 Jul 16.

Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.

Objective: To compare the frequency of rare variants in genes of the pathophysiologically relevant endosomal Toll-like receptor (eTLR) pathway and any quantifiable differences in variant rarity, predicted deleteriousness, or molecular proximity in patients with systemic lupus erythematosus (SLE) and healthy controls.

Patients And Methods: 65 genes associated with the eTLR pathway were identified by literature search and pathway analysis. Using next generation sequencing techniques, these were compared in two randomised cohorts of patients with SLE (n = 114 and n = 113) with 197 healthy controls. Read More

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Case Report: Systemic Sclerosis After Covid-19 Infection.

Serena Fineschi

Front Immunol 2021;12:686699. Epub 2021 Jun 28.

Department of Public Health and Caring Sciences, Unit of General Practice, Uppsala University, Uppsala, Sweden.

The coronavirus disease (COVID-19) is a respiratory tract infection caused by the new virus SARS-CoV-2. The acute phase of the infection may in certain individuals be followed by another longer phase of disease (long COVID) of unknown etiology probably associated in certain cases with autoimmune activation. It has been shown that COVID-19 can trigger autoantibody production and in genetically predisposed patients may cause the onset or exacerbation of autoimmune diseases. Read More

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Inhibition of Rag GTPase signaling in mice suppresses B cell responses and lymphomagenesis with minimal detrimental trade-offs.

Cell Rep 2021 Jul;36(2):109372

Metabolism and Cell Signaling Laboratory, Spanish National Cancer Research Centre (CNIO), Melchor Fernandez Almagro 3, Madrid 28029, Spain. Electronic address:

B lymphocytes are exquisitely sensitive to fluctuations in nutrient signaling by the Rag GTPases, and 15% of follicular lymphomas (FLs) harbor activating mutations in RRAGC. Hence, a potential therapeutic approach against malignant B cells is to inhibit Rag GTPase signaling, but because such inhibitors are still to be developed, efficacy and safety remain unknown. We generated knockin mice expressing a hypomorphic variant of RagC (Q119L); RagC mice are viable and show attenuated nutrient signaling. Read More

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Lymphocytes subsets in correlation with clinical profile in CVID patients without monogenic defects.

Expert Rev Clin Immunol 2021 Jul 27:1-11. Epub 2021 Jul 27.

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

Common variable immunodeficiency (CVID) patients experience clinical manifestations rather than recurrent respiratory infections including autoimmunity, enteropathy, and lymphoproliferation. We evaluated the correlation of lymphocyte subpopulations with such manifestations. Twenty-six genetically unsolved CVID patients were subdivided into four phenotypes: infection only (IO), autoimmunity (AI), chronic enteropathy (CE), and lymphoproliferative disorders (LP) and examined for lymphocyte subsets by flow cytometry and TCD4 proliferation by Carboxyfluorescein succinimidyl ester (CFSE) test. Read More

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Effects of Probiotic Bacteria on the Gut Microbiota in Children With Celiac Disease Autoimmunity: A Placebo-Controlled and Randomized Clinical Trial.

Front Nutr 2021 25;8:680771. Epub 2021 Jun 25.

The Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.

Disturbances of the gut microbiota may influence the development of various autoimmune diseases. This study investigated the effects of supplementations with the probiotic bacteria, HEAL9 and 8700:2, on the microbial community in children with celiac disease autoimmunity (CDA). The study included 78 genetically predisposed children for celiac disease with elevated levels of tissue transglutaminase autoantibodies (tTGA) signaling for ongoing CDA. Read More

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Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation.

Front Cell Dev Biol 2021 21;9:664305. Epub 2021 Jun 21.

Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, United States.

Recent epidemiological studies have found an alarming trend of increased cancer incidence in adults younger than 50 years of age and projected a substantial rise in cancer incidence over the next 10 years in this age group. This trend was exemplified in the incidence of non-cardia gastric cancer and its disproportionate impact on non-Hispanic white females under the age of 50. The trend is concurrent with the increasing incidence of autoimmune diseases in industrialized countries, suggesting a causal link between the two. Read More

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Newly developed pseudogout arthritis after therapy with MAGE-A4 directed TCR T cells responded to treatment with tocilizumab.

J Immunother Cancer 2021 Jul;9(7)

Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

With durable cancer responses, genetically modified cell therapies are being implemented in various cancers. However, these immune effector cell therapies can cause toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Pseudogout arthritis is an inflammatory arthritis induced by deposition of calcium pyrophosphate dihydrate crystals. Read More

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Syndromic immunodeficiencies: a pediatrician's perspective on selected diseases.

Allergol Immunopathol (Madr) 2021 1;49(4):117-136. Epub 2021 Jul 1.

Department of Pediatric Pneumonology, Allergology and Clinical Immunology, Poznan University of Medical Sciences, 27/33 Szpitalna Street, 60-572 Poznan, Poland, Tel/fax +48 61 8480111.

Background: Syndromic immunodeficiencies are a genetically and pathophysiologically heterogeneous group of inborn errors of immunity. These are characterized by multiple extra immune clinical symptoms and a wide range of immunological phenotypes with increased susceptibility to infections, autoimmune phenomena, immune dysregulation, organ-specific pathology, and malignancy.

Objective: To increase the pediatricians' awareness of this multifaceted group of primary immunodeficiencies in children. Read More

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CAR T cells: building on the CD19 paradigm.

Eur J Immunol 2021 Jul 1. Epub 2021 Jul 1.

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Spearheaded by the therapeutic use of chimeric antigen receptors (CARs) targeting CD19, synthetic immunology has entered the clinical arena. CARs are recombinant receptors for antigen that engage cell surface molecules through the variable region of an antibody and signal through arrayed T cell activating and costimulatory domains. CARs allow redirection of T cell cytotoxicity against any antigen of choice, independent of MHC expression. Read More

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Sialic acid O-acetylation: From biosynthesis to roles in health and disease.

J Biol Chem 2021 Jun 19;297(2):100906. Epub 2021 Jun 19.

Copenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Hubrecht Institute, Utrecht, the Netherlands. Electronic address:

Sialic acids are nine-carbon sugars that frequently cap glycans at the cell surface in cells of vertebrates as well as cells of certain types of invertebrates and bacteria. The nine-carbon backbone of sialic acids can undergo extensive enzymatic modification in nature and O-acetylation at the C-4/7/8/9 position in particular is widely observed. In recent years, the detection and analysis of O-acetylated sialic acids have advanced, and sialic acid-specific O-acetyltransferases (SOATs) and O-acetylesterases (SIAEs) that add and remove O-acetyl groups, respectively, have been identified and characterized in mammalian cells, invertebrates, bacteria, and viruses. Read More

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Mechanistic underpinning of an inside-out concept for autoimmunity in multiple sclerosis.

Ann Clin Transl Neurol 2021 Jun 22. Epub 2021 Jun 22.

Department Anatomy and Neuroscience, University Medical Center Amsterdam, Amsterdam, The Netherlands.

The neuroinflammatory disease multiple sclerosis is driven by autoimmune pathology in the central nervous system. However, the trigger of the autoimmune pathogenic process is unknown. MS models in immunologically naïve, specific-pathogen-free bred rodents support an exogenous trigger, such as an infection. Read More

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Investigating Target Gene Function in a CD40 Agonistic Antibody-induced Colitis Model using CRISPR/Cas9-based Technologies.

J Vis Exp 2021 Jun 2(172). Epub 2021 Jun 2.

AbbVie, Cambridge Research Center;

The immune system functions to defend humans against foreign invaders such as bacteria and viruses. However, disorders of the immune system may lead to autoimmunity, inflammatory disease, and cancer. The inflammatory bowel diseases (IBD)-Crohn's disease (CD) and ulcerative colitis (UC)-are chronic diseases marked by relapsing intestinal inflammation. Read More

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Precision Medicine in Graves' Disease: CD40 Gene Variants Predict Clinical Response to an Anti-CD40 Monoclonal Antibody.

Front Endocrinol (Lausanne) 2021 4;12:691781. Epub 2021 Jun 4.

Department of Medicine, Albert Einstein College of Medicine, New York, NY, United States.

Background: CD40, a key co-stimulatory molecule expressed on antigen-presenting cells, is genetically associated with a number of autoimmune diseases including Graves' disease (GD). Therefore, recent therapies targeting CD40 have been developed, including the anti-CD40 monoclonal antibody Iscalimab. In a recent pilot study, Iscalimab was shown to induce clinical remission in ~ 50% of GD patients, but the reason why only 50% of GD patients responded is not known. Read More

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Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity.

J Exp Med 2021 Aug 4;218(8). Epub 2021 Jun 4.

Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN.

T reg cells bearing a diverse antigen receptor repertoire suppress pathogenic T cells and maintain immune homeostasis during their long lifespan. How their robust function is determined genetically remains elusive. Here, we investigate the regulatory space of the cis-regulatory elements of T reg lineage-specifying factor Foxp3. Read More

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Pemphigus Vulgaris After COVID-19: a Case of Induced Autoimmunity.

SN Compr Clin Med 2021 May 27:1-5. Epub 2021 May 27.

Department of Pathology, Federal University of Pernambuco, Recife, PE Brazil.

Bullae autoimmune diseases can be induced by environmental factors in a genetically susceptible individual, and viruses may be important triggers for this process. Coronavirus disease 2019 (COVID-19) is a multisystemic disease known for developing many types of skin lesions. However, little is known about post-COVID-19 manifestations. Read More

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Tenascin-C in Heart Diseases-The Role of Inflammation.

Int J Mol Sci 2021 May 29;22(11). Epub 2021 May 29.

Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.

Tenascin-C (TNC) is a large extracellular matrix (ECM) glycoprotein and an original member of the matricellular protein family. TNC is transiently expressed in the heart during embryonic development, but is rarely detected in normal adults; however, its expression is strongly up-regulated with inflammation. Although neither TNC-knockout nor -overexpressing mice show a distinct phenotype, disease models using genetically engineered mice combined with in vitro experiments have revealed multiple significant roles for TNC in responses to injury and myocardial repair, particularly in the regulation of inflammation. Read More

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TagSNP approach for HLA risk allele genotyping of Saudi celiac disease patients: effectiveness and pitfalls.

Biosci Rep 2021 Jun;41(6)

Pediatric Gastroenterology Unit, Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

Background: Celiac disease (CD) is a genetically complex autoimmune disease which is triggered by dietary gluten. Human leukocyte antigen (HLA) class II genes are known to act as high-risk markers for CD, where >95% of CD patients carry (HLA), DQ2 and/or DQ8 alleles. Therefore, the present study was conducted to investigate the distribution of HLA haplotypes among Saudi CD patients and healthy controls by using the tag single nucleotide polymorphisms (SNP). Read More

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Basophils, a neglected minority in the immune system, have come into the limelight at last.

Int Immunol 2021 May 2. Epub 2021 May 2.

Inflammation, Infection and Immunity Laboratory, TMDU Advanced Research Institute, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.

Basophils, the rarest granulocytes, were identified by Paul Ehrlich more than 140 years ago, much earlier than the discovery of T and B cells. Unfortunately, basophils were often mixed up with tissue-resident mast cells because of some phenotypic similarities between them and considered erroneously as minor relatives or blood-circulating precursors of mast cells. Moreover, basophil research was hindered by the rarity of basophils and the paucity of useful analytical tools, and therefore basophils had often been neglected in immunological studies. Read More

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Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic defects in cytotoxicity.

J Allergy Clin Immunol 2021 May 24. Epub 2021 May 24.

Division of Pediatric Hematology and Oncology, Department of Pediatrics, University Hospital Erlangen, Erlangen, Germany.

Background: Rubella virus-induced granulomas have been described in patients with various inborn errors of immunity. Most defects impair T-cell immunity, suggesting a critical role of T cells in rubella elimination. However, the molecular mechanism of virus control remains elusive. Read More

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Simultaneous Onset of Mycobacterium kansasii Pulmonary Infection and Systemic Lupus Erythematosus: A Case Report.

Am J Case Rep 2021 May 19;22:e929866. Epub 2021 May 19.

Division of Rheumatology, Università Cattolica del Sacro Cuore, Rome, Italy.

BACKGROUND Systemic lupus erythematosus (SLE) is a systemic autoimmune disease resulting from dysregulation of the immune response. In genetically predisposed subjects, infections reputedly trigger an immune activation leading to autoimmunity and overt autoimmune diseases such as SLE. CASE REPORT We report the case of a 19-year-old woman who presented to our hospital reporting high-grade fever, dry cough, and polyarthralgia despite a course of empiric antibiotic and steroid therapy administered by her general practitioner (GP). Read More

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Parechovirus Infection in Early Childhood and Association With Subsequent Celiac Disease.

Am J Gastroenterol 2021 04;116(4):788-795

1Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway; 2Department of Paediatric, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic; 3Department of Pediatrics, Østfold Hospital Trust, Grålum, Norway; 4Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg and Queen Silvia Children's Hospital, Gothenburg, Sweden; 5Division of Institute Resources, Department of IT and e-health, Norwegian Institute of Public Health, Oslo, Norway; 6Department of Pediatric Research, Oslo University Hospital, Oslo, Norway.

Introduction: To test whether parechovirus and anellovirus, frequent enteric viruses, were associated with subsequent celiac disease (CD). We hypothesized that children who later developed CD would have increased frequency of parechovirus infections before transglutaminase 2 (TG2) antibody development. Anellovirus testing was exploratory, as a potential marker of immune status. Read More

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Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency.

N Engl J Med 2021 05 11;384(21):2002-2013. Epub 2021 May 11.

From the Departments of Microbiology, Immunology, and Molecular Genetics (D.B.K., K.L.S., D.A.C.-S., D.T., A.D., A. Icreverzi, P.B., B.C.F., R.P.H., M.C., A.Y., K.M.C., C.E.C., R.Z.), Pediatrics (D.B.K., T.B.M., S.D.O., S.S.), and Pathology and Laboratory Medicine (G.M.C.) and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research (D.B.K., G.M.C.), University of California, Los Angeles (UCLA), and the Department of Pharmaceutical Services, Ronald Reagan UCLA Medical Center (J.T.), Los Angeles, and Stanford School of Medicine, Palo Alto (A.J.S.) - all in California; University College London Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children NHS Foundation Trust (C.B., J.X.-B., V.T., K. Soni, K. Snell, D.L.-R., K.F.B., K.C.G., C.R., N.I., S.A., H.R., C.U., A.J.T., H.B.G.), and Orchard Therapeutics (Europe) (D.A.C.-S., S.A., F.L., M.K., A.S., H.B.G.) - all in London; the National Institute of Allergy and Infectious Diseases (H.L.M.) and the National Human Genome Research Institute (E.G., R.S., F.C.), National Institutes of Health, Bethesda, MD; Cure 4 The Kids Foundation, Las Vegas (A. Ikeda); Cincinnati Children's Hospital Medical Center, Cincinnati (L.R.); Indiana University School of Medicine, Indianapolis (K.C.); Duke University, Durham, NC (R.P., R.H.B., M.H.); Division of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland (F.C.); and GeneWerk (M.Z., R.H., I.L., M.S.) and the German Cancer Research Center and the National Center for Tumor Diseases (M.Z., M.S.) - all in Heidelberg, Germany.

Background: Severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency (ADA-SCID) is a rare and life-threatening primary immunodeficiency.

Methods: We treated 50 patients with ADA-SCID (30 in the United States and 20 in the United Kingdom) with an investigational gene therapy composed of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with a self-inactivating lentiviral vector encoding human . Data from the two U. Read More

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Autoimmune B Cell Repertoire in a Mouse Model of Sjögren's Syndrome.

Front Immunol 2021 23;12:666545. Epub 2021 Apr 23.

Immunology Unit, Department of Biomedical Sciences, Medical School, University of Barcelona, Barcelona, Spain.

In genetically prone individuals, chronic immune activation may lead to expansion of autoreactive lymphocyte clones that can induce organ damage developing autoimmune disorders. Sjögren's Syndrome (SjS) is a systemic chronic autoimmune disease that primarily affects exocrine glands. Despite the accumulated evidences of profound B-cell alterations of humoral immunity, the repertoire and development of B-cell autoreactivity in SjS remains to be determined. Read More

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Polymorphism in BACH2 gene is a marker of polyglandular autoimmunity.

Endocrine 2021 May 8. Epub 2021 May 8.

Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland.

Purpose: Genetically predisposed individuals may develop several autoimmune diseases-autoimmune polyendocrine syndromes (APS). APS types 2-4, are complex disorders, which combine various organ-specific autoimmune conditions. Recent reports support the considerable role of the BACH2 gene in immune cell differentiation and shifting the T-cell balance towards regulatory T-cells. Read More

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Clinical, immunological, and genetic features in 780 patients with autoimmune lymphoproliferative syndrome (ALPS) and ALPS-like diseases: A systematic review.

Pediatr Allergy Immunol 2021 May 8. Epub 2021 May 8.

Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.

Background: Autoimmune lymphoproliferative syndrome (ALPS) is a group of genetic disorders characterized by early-onset lymphoproliferation, autoimmune cytopenias, and susceptibility to lymphoma. The majority of ALPS patients carry heterozygous germline mutations in the TNFRSF6 gene. In this study, we conducted a systematic review of patients with ALPS and ALPS-like syndrome. Read More

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Medical Records-Based Genetic Studies of the Complement System.

J Am Soc Nephrol 2021 Aug 3;32(8):2031-2047. Epub 2021 May 3.

Division of Nephrology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York

Background: Genetic variants in complement genes have been associated with a wide range of human disease states, but well-powered genetic association studies of complement activation have not been performed in large multiethnic cohorts.

Methods: We performed medical records-based genome-wide and phenome-wide association studies for plasma C3 and C4 levels among participants of the Electronic Medical Records and Genomics (eMERGE) network.

Results: In a GWAS for C3 levels in 3949 individuals, we detected two genome-wide significant loci: chr. Read More

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GILZ Regulates the Expression of Pro-Inflammatory Cytokines and Protects Against End-Organ Damage in a Model of Lupus.

Front Immunol 2021 6;12:652800. Epub 2021 Apr 6.

Monash University Centre for Inflammatory Disease, School of Clinical Sciences at Monash Health, Melbourne, VIC, Australia.

Glucocorticoid-induced leucine zipper (GILZ) mimics many of the anti-inflammatory effects of glucocorticoids, suggesting it as a point of therapeutic intervention that could bypass GC adverse effects. We previously reported that GILZ down-regulation is a feature of human SLE, and loss of GILZ permits the development of autoantibodies and lupus-like autoimmunity in mice. To further query the contribution of GILZ to protection against autoimmune inflammation, we studied the development of the lupus phenotype in Lyn-deficient (Lyn) mice in which GILZ expression was genetically ablated. Read More

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