ArticleJournal of clinical immunology2020
Expanding Clinical Phenotype and Novel Insights into the Pathogenesis of ICOS Deficiency.
Article in Journal of clinical immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Beyond B cells: T and Innate Immune Mechanisms of Autoimmunity in Common Variable Immunodeficiency.Clinical reviews in allergy & immunology · 2026Review
- A Flow Cytometry-Based Assay to Quantify the Binding of Transmembrane Ligands to Their Cognate Receptors Using Fluorescent Virus-Like Particles.Bio-protocol · 2026Article
- A flow cytometry-based assay to quantify the binding of transmembrane ligands to their cognate receptors using fluorescent virus-like particles.bioRxiv : the preprint server for biology · 2026Article
- Navigating primary and secondary immunodeficiency intersections: how to find IEI hidden within SID.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2026Review
- Molecular analysis and immunological characterization of a founder mutation causing ARPC1B deficiency.Genes and immunity · 2026Article
- Monogenic inflammatory bowel disease: An unfolding enigma.World journal of clinical pediatrics · 2025Review
- Advances in Understanding Intestinal Homeostasis: Lessons from Inflammatory Bowel Disease and Monogenic Intestinal Disorder Pathogenesis.International journal of molecular sciences · 2025Review
- Human immunity to fungal infections.The Journal of experimental medicine · 2025Review
- Research trajectory of the mechanism of preeclampsia: a scientometric perspective.Journal of health, population, and nutrition · 2025Article
- Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases.Pathogens (Basel, Switzerland) · 2023Review
- Identification of novel NFKB1 and ICOS frameshift variants in patients with CVID.Clinical and experimental immunology · 2023Article
- Infections in Inborn Errors of Immunity with Combined Immune Deficiency: A Review.Pathogens (Basel, Switzerland) · 2023Review
- Clinical and Immunologic Characteristics of Non-Hematologic Cancers in Patients with Inborn Errors of Immunity.Cancers · 2023Article
- Recalcitrant Cutaneous Warts in a Family with Inherited ICOS Deficiency.The Journal of investigative dermatology · 2022Article
- The pediatric common variable immunodeficiency - from genetics to therapy: a review.European journal of pediatrics · 2022Review
- Inherited immunodeficiencies associated with proximal and distal defects in T cell receptor signaling and co-signaling.Biomedical journal · 2022Review
- Autoimmune Cytopenias in Common Variable Immunodeficiency Are a Diagnostic and Therapeutic Conundrum: An Update.Frontiers in immunology · 2022Review
- A Patient with Novel ICOS Mutation Presented with Progressive Loss of B Cells.Journal of clinical immunology · 2021Article
- Specific Immune Response and Cytokine Production in CD70 Deficiency.Frontiers in pediatrics · 2021Article
Corrections and comments
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Authors and funding
15 authors at 10 institutions in 4 countries.
Funding
Abstract
backgroundInducible T cell co-stimulator (ICOS) deficiency has been categorized as a combined immunodeficiency often complicated by enteropathies, autoimmunity, lymphoproliferation, and malignancy. We report seven new patients and four novel ICOS mutations resulting in a common variable immunodeficiency (CVID)-like phenotype and show that dysregulated IL-12 release, reduced cytotoxic T lymphocyte-associated protein 4 (CTLA4) expression, and skewing towards a Th1-dominant phenotype are all associated with inflammatory complications in this condition.
methodsA combination of whole exome and Sanger sequencing was used to identify novel mutations. Standard clinical and immunological evaluation was performed. FACS and ELISA-based assays were used to study cytokine responses and ICOS/ICOSL/CTLA4 expression following stimulation of whole blood and PBMCs with multiple TLR ligands, anti-CD3, and PHA.
resultsFour novel ICOS mutations included homozygous c.323_332del, homozygous c.451C>G, and compound heterozygous c.58+1G>A/c.356T>C. The predominant clinical phenotype was that of antibody deficiency associated with inflammatory complications in 4/7 patients. Six out of seven patients were treated with immunoglobulin replacement and one patient died from salmonella sepsis. All patients who were tested showed reduced IL-10 and IL-17 cytokine responses, normal IL-1β, IL6, and TNF release following LPS stimulation and highly elevated IL-12 production in response to combined LPS/IFNγ stimulation. This was associated with skewing of CD4
conclusionsICOS deficiency is associated with defective T cell activation, with simultaneously enhanced stimulation of monocytes. The latter is likely to result from a lack of ICOS/ICOSL interaction which might be necessary to provide negative feedback which limits monocytes activation.
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