A5062601012- Immunodeficiency and Autoimmune Disorders
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Antifungal resistance and susceptibility
- T-cell and B-cell Immunology
- Fungal Infections and Studies
- Blood disorders and treatments
- interferon and immune responses
- Mycobacterium research and diagnosis
- Diabetes and associated disorders
- Inflammasome and immune disorders
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Nail Diseases and Treatments
- Adrenal Hormones and Disorders
- Pediatric health and respiratory diseases
- RNA and protein synthesis mechanisms
- Genomics and Rare Diseases
- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- RNA regulation and disease
- Whipple's Disease and Interleukins
- Cytokine Signaling Pathways and Interactions
- Psoriasis: Treatment and Pathogenesis
Inserm
2016-2025
Université Paris Cité
2016-2025
Institut des Maladies Génétiques Imagine
2016-2025
Rockefeller University
2016-2025
Human Genetic of Infectious Diseases
2012-2025
Hospital for Sick Children
2024-2025
SickKids Foundation
2024-2025
Sorbonne Paris Cité
2011-2024
University of Pamplona
2024
University College London
2024
Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 987 patients with life-threatening disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), 13 types IFN-α (36), or both (52) onset critical disease; a few also auto-Abs other three type I IFNs. The neutralize ability corresponding IFNs to block...
MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 (IL-1Rs). deficiency in mice leads to susceptibility broad range of pathogens experimental settings infection. We describe distinct situation natural setting human Nine children with autosomal recessive suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, normal resistance other microbes....
Monocytes are effectors of the inflammatory response to microbes. Human CD14+ monocytes specialize in phagocytosis and production reactive oxygen species secrete cytokines a broad range microbial cues. Here, we have characterized functions human that lack CD14 (CD14dim) express CD16. CD14dim were genetically distinct from natural killer cells. Gene expression analyses indicated similarities with murine patrolling Gr1dim monocytes, they patrolled endothelium blood vessels after adoptive...
Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in animal models, but their contribution host defense natural ecosystems is unknown. We report a dominant-negative TLR3 allele otherwise healthy children with herpes simplex virus 1 (HSV-1) encephalitis. expressed the central nervous system (CNS), where it required control HSV-1, which spreads from epithelium CNS via cranial nerves. also epithelial dendritic cells, apparently use TLR3-independent pathways...
Chronic mucocutaneous candidiasis disease (CMCD) is characterized by recurrent or persistent infections of the skin, nails, and oral genital mucosae caused Candida albicans and, to a lesser extent, Staphylococcus aureus, in patients with no other infectious autoimmune manifestations. We report two genetic etiologies CMCD: autosomal recessive deficiency cytokine receptor, interleukin-17 receptor A (IL-17RA), dominant interleukin-17F (IL-17F). IL-17RA complete, abolishing cellular responses...
Generalized pustular psoriasis is a life-threatening disease of unknown cause. It characterized by sudden, repeated episodes high-grade fever, generalized rash, and disseminated pustules, with hyperleukocytosis elevated serum levels C-reactive protein, which may be associated plaque-type psoriasis.
Abstract We report the updated classification of inborn errors immunity, compiled by International Union Immunological Societies Expert Committee. This documents key clinical and laboratory features 55 novel monogenic gene defects, 1 phenocopy due to autoantibodies, that have either been discovered since previous update (published January 2020) or were characterized earlier but confirmed expanded in subsequent studies. While variants additional genes associated with immune diseases reported...
Members of the Toll-like receptor (TLR) and interleukin-1 (IL-1R) superfamily share an intracytoplasmic Toll–IL-1 (TIR) domain, which mediates recruitment receptor–associated kinase (IRAK) complex via TIR-containing adapter molecules. We describe three unrelated children with inherited IRAK-4 deficiency. Their blood fibroblast cells did not activate nuclear factor κB mitogen-activated protein (MAPK) failed to induce downstream cytokines in response any known ligands TIR-bearing receptors....
Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 47 patients from 20 kindreds with AD CMCD. Previously described mutant alleles are loss-of-function and cause predisposition to mycobacterial impaired STAT1-dependent cellular responses IFN-γ. Other AR intracellular bacterial viral diseases, IFN-α/β, IFN-γ,...
Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is the most common form of sporadic viral in western countries. Its pathogenesis remains unclear, as it affects otherwise healthy patients and only a small minority HSV-1-infected individuals. Here, we elucidate genetic etiology for HSE two children with autosomal recessive deficiency intracellular protein UNC-93B, resulting impaired cellular interferon-alpha/beta -lambda antiviral responses. can result from single-gene immunodeficiency that...
Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera all 33 tested, as detected by multiplex particle-based flow cytometry. The auto-Abs and were specific five shown Western blotting. IL-17A neutralizing only patient bioassays activity. None...
Tuberculosis Vaccine Conundrum Some children experience severe clinical disease when they are vaccinated against tuberculosis, an attenuated live vaccine that is normally innocuous in humans. Several germline mutations have been identified account for this susceptibility, and now Bogunovic et al. (p. 1684 , published online 2 August) add another to the list— ISG15 . Uncovering mutation, which inherited autosomal recessive manner, was a surprise because studies with mice deficient showed...
The cytokines controlling the development of human interleukin (IL) 17–producing T helper cells in vitro have been difficult to identify. We addressed question IL-17–producing vivo by quantifying production and secretion IL-17 fresh ex vivo, cell blasts expanded from patients with particular genetic traits affecting transforming growth factor (TGF) β, IL-1, IL-6, or IL-23 responses. Activating mutations TGFB1, TGFBR1, TGFBR2 (Camurati-Engelmann disease Marfan-like syndromes) loss-of-function...
Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- receptor-mediated immunity. We documented the clinical features outcome of 48 patients with IRAK-4 deficiency 12 MyD88 deficiency, from 37 kindreds in 15 countries. The were indistinguishable. There no severe viral, parasitic, fungal diseases, range bacterial infections was narrow. Noninvasive occurred 52 patients, a high incidence...
A surprising immune twist for RORC The system needs its full array of soldiers—including cells and the molecules they secrete—to optimally protect host. When this isn't case, minor infections can become chronic or even deadly. Markle et al. report discovery seven individuals carrying loss-of-function mutations in RORC, which encodes transcription factors RORγ RORγT. These lacked that produce cytokine interleukin-17, causing them to suffer from candidiasis. RORC-deficient also exhibited...
Human interleukin (IL) 1 receptor–associated kinase 4 (IRAK-4) deficiency is a recently discovered primary immunodeficiency that impairs Toll/IL-1R immunity, except for the Toll-like receptor (TLR) 3– and TLR4–interferon (IFN)-a/b pathways. The clinical immunological phenotype remains largely unknown. We diagnosed up to 28 patients with IRAK-4 deficiency, tested blood TLR responses individual leukocyte subsets, multiple cytokines. patients' peripheral mononuclear cells (PBMCs) did not induce...
Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It characterized extensive dermal subcutaneous tissue invasion frequent dissemination to the lymph nodes and, occasionally, central nervous system. The condition different from common superficial dermatophyte has been reported in patients with no known immunodeficiency. Patients are mostly North African, consanguineous, multiplex families, which strongly suggests mendelian genetic...
Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort 1,202 patients 0.5 99 52.9 with unexplained pneumonia. None the 331 asymptomatically or mildly infected 1.3 102 38.7 tested carry such (p = 3.5 × 10-5). The phenotypes five hemizygous relatives...