717 results match your criteria: "Necker Hospital for Sick Children[Affiliation]"

Autosomal recessive deficiency of the IFNAR1 or IFNAR2 chain of the human type I IFN receptor abolishes cellular responses to IFN-α, -β, and -ω, underlies severe viral diseases, and is globally very rare, except for IFNAR1 and IFNAR2 deficiency in Western Polynesia and the Arctic, respectively. We report 11 human IFNAR1 alleles, the products of which impair but do not abolish responses to IFN-α and -ω without affecting responses to IFN-β. Ten of these alleles are rare in all populations studied, but the remaining allele (P335del) is common in Southern China (minor allele frequency ≈2%).

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Common variable immunodeficiency: autoimmune cytopenias and advances in molecular diagnosis.

Hematology Am Soc Hematol Educ Program

December 2024

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.

Common variable immunodeficiency (CVID) is one of the most common groups of human inborn errors of immunity. In addition to infections resulting from insufficient levels of immunoglobulins and antibodies, a significant proportion of patients develop autoimmune cytopenias, especially immune thrombocytopenia, hemolytic anemia, or neutropenia. They may be the initial manifestation of CVID in a patient who has not had significant infections, and similar episodes may recur at intervals over time.

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Human DBR1 deficiency impairs stress granule-dependent PKR antiviral immunity.

J Exp Med

January 2025

Division Life Sciences and Medicine, Department of General Surgery, The First Affiliated Hospital of USTC, Key Laboratory of Immune Response and Immunotherapy, Center Advanced Interdisciplinary Science and Biomedicine IHM, University of Science and Technology of China, Hefei, China.

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Inborn errors of immunity reveal molecular requirements for generation and maintenance of human CD4 IL-9-expressing cells.

J Allergy Clin Immunol

November 2024

Garvan Institute of Medical Research, Darlinghurst, Australia; School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales (UNSW), Sydney, Australia. Electronic address:

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Article Synopsis
  • Inborn errors of immunity (IEI) involve various disorders that can be hard to diagnose early, as shown in a Brazilian patient with severe combined immunodeficiency (SCID) diagnosed at 6 months old due to multiple infections.
  • After undergoing hematopoietic stem cell transplantation (HSCT), the patient experienced recurrent infections and tested positive for SARS-CoV-2 multiple times over six months.
  • Whole exome sequencing revealed a damaging genetic variant in the Janus Kinase 3 (JAK3) gene, suggesting its role in disrupting protein function and contributing to SCID's pathogenesis.
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  • * Researchers differentiated induced pluripotent stem cells from both a CF patient and a healthy donor into macrophages to study the effects of CFTR deficiency on macrophage function.
  • * The study found that CF macrophages (iMac) had reduced ability to kill bacteria, altered cellular environment, and exhibited signs of inflammation and dysfunctional responses, indicating an impaired immune response in CF.
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Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signaling.

Immunity

December 2024

Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW 2052, Australia; Clinical Immunogenomics Research Consortium Australasia (CIRCA), Darlinghurst, NSW 2010, Australia. Electronic address:

Article Synopsis
  • T follicular helper (Tfh) cells, which are important for antibody production, rely heavily on the immunoreceptor PD-1, and its deficiency leads to weakened Tfh functions and impaired immune responses in mice.
  • Individuals lacking PD-1 or PD-L1 demonstrate fewer memory B cells and diminished antibody responses, highlighting the critical role of these molecules in immune system functionality.
  • PD-1 influences both the intrinsic and extrinsic aspects of B cell memory and antibody production, suggesting that disruptions in PD-1 signaling can lead to complications in immune responses, especially during anti-PD-1-PD-L1 therapies.
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We studied a family with three male individuals across two generations affected by common variable immune deficiency (CVID). We identified a novel missense heterozygous variant (c.2602T>A:p.

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2q33 Deletions Underlying Syndromic and Non-syndromic CTLA4 Deficiency.

J Clin Immunol

November 2024

Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), Paris, EU, France.

Purpose: CTLA4 deficiency is an inborn error of immunity (IEI) due to heterozygosity for germline loss-of-function variants of the CTLA4 gene located on chromosome 2q33.2. CTLA4 deficiency underlies pleiotropic immune and lymphoproliferation-mediated features with incomplete penetrance.

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Genetic defects of brain immunity in childhood herpes simplex encephalitis.

Nature

November 2024

St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.

Article Synopsis
  • Herpes simplex virus 1 (HSV-1) encephalitis (HSE) is a serious viral brain infection that primarily affects children, with genetic factors playing a significant role in some cases.
  • About 8-10% of childhood HSE cases are linked to specific genetic mutations, allowing for innovative diagnostic and treatment strategies.
  • The review highlights how the brain's antiviral defense mechanisms, including both known and newly discovered pathways, are compromised in HSE, emphasizing the importance of neuron-specific immunity beyond just traditional immune cells.
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Purpose: The pathogenesis of life-threatening coronavirus disease 2019 (COVID-19) pneumonia in ICU patients can involve pre-existing auto-antibodies (auto-Abs) neutralizing type I interferons (IFNs). The impact of these auto-Abs on SARS-CoV-2 clearance in the lower respiratory tract (LRT) is unclear.

Methods: We performed a retrospective study in 99 ICU patients with COVID-19 pneumonia between March and May 2020.

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Auto-Abs neutralizing type I IFNs in patients with severe Powassan, Usutu, or Ross River virus disease.

J Exp Med

December 2024

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Necker Hospital for Sick Children, Paris, France.

Arboviral diseases are a growing global health concern. Pre-existing autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) can underlie encephalitis due to West Nile virus (WNV) (∼40% of patients) and tick-borne encephalitis (TBE, due to TBE virus [TBEV]) (∼10%). We report here that these auto-Abs can also underlie severe forms of rarer arboviral infections.

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Phenotypes of 126 Moroccan HIES patients according to NIH Score.

Tunis Med

October 2024

Laboratory of Clinical Immunology, Inflammation, and Allergy (LICIA), Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.

Article Synopsis
  • Hyper-IgE syndrome (HIES) is an inherited immune disorder marked by high IgE levels, chronic eczema, and recurrent staphylococcal infections.
  • This study examined Moroccan patients likely suffering from HIES, focusing on their clinical and immunological features based on specific NIH criteria over a 25-year period.
  • Findings revealed a wide range of symptoms, with eczema and skin infections being the most common, emphasizing the need for molecular analysis for accurate diagnosis and treatment in light of overlapping symptoms.
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Comprehensive Catalog of Variants Potentially Associated with Hidradenitis Suppurativa, Including Newly Identified Variants from a Cohort of 100 Patients.

Int J Mol Sci

September 2024

Team 16, Vaccine Research Institute (VRI), INSERM U955, Institut Mondor de Recherche Biomédicale (IMRB), Henri-Mondor Hospital, UPEC, 94000 Créteil, France.

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by painful, recurrent abscesses, nodules, and scarring, primarily in skin folds. The exact causes of HS are multifactorial, involving genetic, hormonal, and environmental factors. It is associated with systemic diseases such as metabolic syndrome and inflammatory bowel disease.

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  • * A study examined 131 female patients with X-linked dominant incontinentia pigmenti (IP), finding that 36% produced autoantibodies against IFN-α and/or IFN-ω, significantly higher than age-matched controls.
  • * The presence of these autoantibodies is linked to an abnormally small thymus and predisposes patients to life-threatening viral infections, while those without these autoantibodies do not face the same risk.
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IL-7-dependent and -independent lineages of IL-7R-dependent human T cells.

J Clin Invest

October 2024

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.

Article Synopsis
  • Some babies with a specific mutation in the IL7R gene have a serious immune problem called SCID, where they lack a certain type of immune cells called T cells, but still have normal B and NK cells.
  • In a study of 6 adults who have a similar genetic issue, they showed low levels of T cells but had relatively normal levels of other immune cells, indicating a more specific problem in T cell development.
  • Even though their T cells didn’t grow well in the lab, the study hints that there might be another way T cells can develop that doesn’t depend solely on the IL-7 cytokine.
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Dupilumab in atopic-dermatitis-like eczema associated with inborn errors of immunity: A nationwide study.

J Am Acad Dermatol

January 2025

Department of Dermatology, Reference Center for Genodermatoses (MAGEC), Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris Cité University, Paris, France; Imagine Institute, INSERM UMR1163, Paris Cité University, Paris, France. Electronic address:

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  • Interferons (IFNs) are important for how our bodies respond to viruses, and this study used CRISPR to find human genes affecting SARS-CoV-2 infection with and without IFN.
  • The research identified 28 key genes linked to COVID-19, especially those involving the IFN pathway, including PLSCR1, which can limit virus entry without needing IFN.
  • PLSCR1’s ability to block SARS-CoV-2 was reduced by the overexpression of TMPRSS2, and some virus variants have evolved to bypass PLSCR1’s defense, suggesting ongoing challenges in controlling the virus.
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Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients.

J Exp Med

October 2024

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Necker Hospital for Sick Children, Paris, France.

Article Synopsis
  • Tick-borne encephalitis virus (TBEV), spread through tick bites, mostly causes mild illness in over 90% of cases, but can lead to varying degrees of encephalitis in some individuals.
  • Around 10% of patients with severe TBE in Austria, Czech Republic, and France have auto-antibodies (auto-Abs) that neutralize certain types of interferon (IFN), which are important for immune response, while only about 1% of patients with milder symptoms have them.
  • The presence of these auto-Abs significantly increases the risk of severe TBE, with odds ratios indicating up to a 20.8 times higher chance of severe illness when these auto-Abs are
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A sensitive assay for measuring whole-blood responses to type I IFNs.

Proc Natl Acad Sci U S A

October 2024

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris 75015, France.

Article Synopsis
  • Inborn errors or autoantibodies (auto-Abs) against type I interferons (IFNs) can lead to severe viral infections.
  • Researchers developed a straightforward blood test that can identify these conditions by stimulating blood with glycosylated IFN-α2, -β, or -ω and measuring IP-10 levels.
  • The study found that IP-10 levels in patients with inherited deficiencies only increase with type II IFN (IFN-γ), while those with auto-Abs can still respond to non-neutralized type I IFNs.
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Germline mutations in a G protein identify signaling cross-talk in T cells.

Science

September 2024

Human Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Article Synopsis
  • Researchers studied mutations in a gene that affects a key protein involved in cell signaling, which is linked to severe health issues like impaired immunity in patients.
  • The mutations were found to disrupt normal cell behavior by promoting excessive cell growth and responses to immune signals, specifically T cell receptor stimulation.
  • The mutant protein was shown to interfere with a regulatory protein, leading to heightened activity of important signaling pathways that contribute to cell growth and survival.
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