Benedetta Bigio
A5061818692- Stress Responses and Cortisol
- Genomic variations and chromosomal abnormalities
- Immunodeficiency and Autoimmune Disorders
- Tryptophan and brain disorders
- Genomics and Rare Diseases
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Diet and metabolism studies
- Genetic Associations and Epidemiology
- Neuroendocrine regulation and behavior
- Functional Brain Connectivity Studies
- SARS-CoV-2 and COVID-19 Research
- Mental Health Research Topics
- interferon and immune responses
- Neuroscience and Neuropharmacology Research
- Cancer Genomics and Diagnostics
- Immune Response and Inflammation
- Whipple's Disease and Interleukins
- Health, Environment, Cognitive Aging
- Adipose Tissue and Metabolism
- Genetic Mapping and Diversity in Plants and Animals
- Neuroinflammation and Neurodegeneration Mechanisms
- Diabetes and associated disorders
- Genetics and Neurodevelopmental Disorders
- Birth, Development, and Health
Nathan Kline Institute for Psychiatric Research
2024-2025
New York University
2022-2025
Rockefeller University
2014-2022
META Health
2022
Lehigh University
2022
Indiana University School of Medicine
2022
Institut des Maladies Génétiques Imagine
2018-2021
Université Paris Cité
2018-2021
Inserm
2018-2021
UCLA Health
2018
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...
The genetics underlying severe COVID-19 immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody dampens IFN response prevent damage from pathogen-induced inflammation. Two studies now examine likelihood affects risk of coronavirus disease 2019 (COVID-19) through components this (see Perspective by Beck Aksentijevich). Q....
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...
Hundreds of patients with autosomal recessive, complete IL-12p40 or IL-12Rβ1 deficiency have been diagnosed over the last 20 years. They typically suffer from invasive mycobacteriosis and, occasionally, mucocutaneous candidiasis. Susceptibility to these infections is thought be due impairments IL-12-dependent IFN-γ immunity and IL-23-dependent IL-17A/IL-17F immunity, respectively. We report here IL-12Rβ2 IL-23R deficiency, lacking responses IL-12 IL-23 only, all whom, unexpectedly, display...
Autosomal recessive IRF7 and IRF9 deficiencies impair type I III IFN immunity underlie severe influenza pneumonitis. We report three unrelated children with A virus (IAV) infection manifesting as acute respiratory distress syndrome (IAV-ARDS), heterozygous for rare TLR3 variants (P554S in two patients P680L the third) causing autosomal dominant (AD) deficiency. AD deficiency can herpes simplex virus-1 (HSV-1) encephalitis (HSE) by impairing cortical neuron-intrinsic to HSV-1. TLR3-mutated...
Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 or RNASEL five unrelated with MIS-C. The cytosolic double-stranded RNA (dsRNA)–sensing generate 2′-5′-linked oligoadenylates (2-5A) activate the single-stranded RNA–degrading ribonuclease L (RNase L). Monocytic cell lines primary myeloid cells OAS1, OAS2, RNase produce excessive amounts cytokines upon dsRNA acute...
Significance Chronic stress alters the hippocampal responses to familiar and novel stressors, behaviorally, physiologically, epigenetically. In aftermath of chronic in WT mice with a BDNF loss-of-function allele without any applied stress, there is window plasticity that allows experiences alter anxiety- depressive-like behaviors, reflected also electrophysiological changes dentate gyrus (DG) vitro. A consistent biomarker mood-related behaviors DG reduced type 2 metabotropic glutamate...
The lack of biomarkers to identify target populations greatly limits the promise precision medicine for major depressive disorder (MDD), a primary cause ill health and disability. endogenously produced molecule acetyl-l-carnitine (LAC) is critical hippocampal function several behavioral domains. In rodents with depressive-like traits, LAC levels are markedly decreased signal abnormal glutamatergic dendritic plasticity. supplementation induces rapid lasting antidepressant-like effects via...
Inborn errors of TLR3-dependent IFN-α/β- and IFN-λ-mediated immunity in the CNS can underlie herpes simplex virus 1 (HSV-1) encephalitis (HSE). The respective contributions IFN-α/β IFN-λ are unknown. We report a child homozygous for genomic deletion entire coding sequence part 3'-UTR last exon IFNAR1, who died HSE at age 2 years. An older cousin following vaccination against measles, mumps, rubella 12 months age, another 17-year-old same variant has had other, less severe, viral illnesses....
Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment CNS cell-intrinsic antiviral immunity. Deficiencies pathway impair immunity to vesicular stomatitis (VSV) and HSV-1 fibroblasts, cortical but not trigeminal neurons. The underlying molecular mechanism is thought involve impaired IFN-α/β induction recognition dsRNA viral intermediates or by-products. However, we show here that human controls constitutive levels IFNB...
Human inborn errors of IFN-γ underlie mycobacterial disease, due to insufficient production by lymphoid cells, impaired myeloid cell responses this cytokine, or both. We report four patients from two unrelated kindreds with intermittent monocytosis and including bacillus Calmette-Guérin-osis disseminated tuberculosis, without any known error IFN-γ. The are homozygous for ZNFX1 variants (p.S959* p.E1606Rfs*10) predicted be loss function (pLOF). There no subjects pLOF in public databases. is a...
Globally, autosomal recessive IFNAR1 deficiency is a rare inborn error of immunity underlying susceptibility to live attenuated vaccine and wild-type viruses. We report seven children from five unrelated kindreds western Polynesian ancestry who suffered severe viral diseases. All the patients are homozygous for same nonsense variant (p.Glu386*). This allele encodes truncated protein that absent cell surface loss-of-function. The fibroblasts do not respond type I IFNs (IFN-α2, IFN-ω, or...
Significance Responsiveness, resistance to, and speed of treatment are major problems for depression. The energetic epigenetic agent acetyl- l -carnitine (LAC) is known to exert rapid antidepressant-like effects in LAC-deficient Flinders Sensitive Line rats. Here, we identified central metabolic-regulator genes (e.g., insulin glucose signaling) ventral dentate gyrus (vDG), a mood-regulatory region, as key factors predisposing depression LAC responsiveness. While improving energy regulation...
Computational analyses of human patient exomes aim to filter out as many nonpathogenic genetic variants (NPVs) possible, without removing the true disease-causing mutations. This involves comparing patient’s exome with public databases remove reported inconsistent disease prevalence, mode inheritance, or clinical penetrance. However, frequent in a given cohort, but absent rare databases, have also been and treated NPVs, rigorous exploration. We report generation blacklist within an in-house...
Next-generation sequencing (NGS) generates large amounts of genomic data and reveals about 20 000 genetic coding variants per individual studied. Several mutation damage prediction scores are available to prioritize variants, but there is currently no application help investigators determine the relevance candidate genes quickly visually from population genetics deleteriousness scores. Here, we present PopViz, a user-friendly, rapid, interactive, mobile-compatible webserver providing...
Abstract SARS-CoV-2 is responsible for the ongoing world-wide pandemic which has already taken more than two million lives. Effective treatments are urgently needed. The enzymatic activity of HECT-E3 ligase family members been implicated in cell egression phase deadly RNA viruses such as Ebola through direct interaction its VP40 Protein. Here we report that NEDD4 and WWP1 interact with ubiquitylate Spike protein. Furthermore, find HECT overexpressed primary samples derived from COVID-19...
Autosomal dominant (AD) NFKB1 deficiency is thought to be the most common genetic etiology of variable immunodeficiency (CVID). However, causal link between variants and CVID has not been demonstrated experimentally genetically, there insufficient biochemical characterization enrichment analysis. We show that cotransfection NFKB1-deficient HEK293T cells (lacking both p105 its cleaved form p50) with a κB reporter, NFKB1/p105, homodimerization-defective RELA/p65 mutant results in p50:p65...