Tom Le Voyer
A5062086306- Immunodeficiency and Autoimmune Disorders
- Diabetes and associated disorders
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- Adrenal Hormones and Disorders
- T-cell and B-cell Immunology
- Respiratory viral infections research
- Blood disorders and treatments
- Long-Term Effects of COVID-19
- Eosinophilic Disorders and Syndromes
- Systemic Lupus Erythematosus Research
- Mosquito-borne diseases and control
- Inflammasome and immune disorders
- Viral Infections and Vectors
- interferon and immune responses
- NF-κB Signaling Pathways
- Systemic Sclerosis and Related Diseases
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Parvovirus B19 Infection Studies
- Cytomegalovirus and herpesvirus research
- Neonatal Respiratory Health Research
- Genetic and Kidney Cyst Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Inserm
2020-2025
Institut des Maladies Génétiques Imagine
2021-2025
Université Paris Cité
2021-2025
Hôpital Saint-Louis
2024-2025
Assistance Publique – Hôpitaux de Paris
2021-2025
Rockefeller University
2021-2024
Hospital for Sick Children
2024
Human Genetic of Infectious Diseases
2022-2024
Clermont Université
2022
Hôpital Necker-Enfants Malades
2021-2022
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found about 10% patients with critical COVID-19 pneumonia, but not subjects asymptomatic infections. We detect auto-Abs 100-fold lower, more physiological, (100 pg/mL, 1/10 dilutions plasma) 13.6% 3,595 COVID-19, including 21% 374 > 80 years, and 6.5% 522 severe COVID-19. These antibodies also detected 18% the 1,124 deceased (aged 20 days-99 years; mean: 70...
Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These were recently reported to account for at least 10% cases life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients 21 kindreds seven countries, aged between 8 48 yr infected SARS-CoV-2 since February 2020. The...
Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported one 12-yr-old patient. Here, we studied seven other previously healthy aged 13 to 80 yr unexplained YFV vaccine–associated disease. One 13-yr-old patient had AR IFNAR2 deficiency. Three vaccinated at the ages 47, 57, and 64 high titers circulating auto-Abs...
Significance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It important to estimate their quantitative impact on mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence these risk death increase with higher in men. Using an unvaccinated sample 1,261 deceased patients 34,159 individuals from general population, we found against IFNs strongly increased...
Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies IFN-α2 alone (five patients) or with IFN-ω (eight from a cohort of 279 (4.7%) aged 6–73 yr influenza pneumonia. Nine four had antibodies high low concentrations, respectively, IFN-α2, six two IFN-ω. The patients’ increased A virus replication in both A549 cells reconstituted human airway epithelia. prevalence...
Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis <1% of infected individuals. We show that ∼35% patients hospitalized for WNV disease (WNVD) six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence these antibodies highest with (∼40%), silent as low general population. odds ratios WNVD relative to those without them population range 19.0 (95% CI 15.0–24.0, P value <10–15) only...
Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize I interferons (IFNs)1,2, conferring a predisposition to life-threatening COVID-19 pneumonia3. Here we report patients NIK or RELB deficiency, specific of autosomal-dominant NF-κB2 also have neutralizing against IFNs and are at higher risk getting pneumonia. In these found only in individuals who heterozygous for variants associated both...
We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only three, plus IFN-ω five, and IFN-α2, IFN-β two; nine patients). Seven (3.8%) Abs at least ng/ml one IFN, whereas the other 12 (6.6%) 100 pg/ml. The auto-Abs neutralized both unglycosylated glycosylated IFNs. also detected pg/ml 4 2,267 uninfected (0.2%) 45 (2%). odds ratios (ORs) life-threatening were, therefore,...
Deficiency of ubiquitin-specific peptidase 18 (USP18) is a severe type I interferonopathy. USP18 down-regulates interferon signaling by blocking the access Janus-associated kinase 1 (JAK1) to receptor. The absence results in unmitigated interferon-mediated inflammation and lethal during perinatal period. We describe neonate who presented with hydrocephalus, necrotizing cellulitis, systemic inflammation, respiratory failure. Exome sequencing identified homozygous mutation at an essential...
To evaluate the efficacy and safety of Janus kinase inhibitors (JAKis) in JDM.We conducted a single-centre retrospective study patients with JDM treated by JAKi follow-up at least 6 months. Proportion clinically inactive disease (CID) within months initiation was evaluated using PRINTO criteria skin Disease Activity Score. Serum IFN-α concentration measured Simoa assay.Nine refractory one new-onset ruxolitinib (n = 7) or baricitinib 3) were included. The main indications for treatment muscle...
Objectives Type-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-β and/or IFN-ω subtypes strong determinants of hypoxemic COVID-19 pneumonia, but their impact on inflammation remains unknown. Methods We retrospectively analysed a monocentric longitudinal cohort 609 SLE. Serum AAbs against IFN-α were quantified by ELISA and functionally assessed abolishment...
Life-threatening “breakthrough” cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie least 15% pneumonia unvaccinated individuals; their contribution hypoxemic breakthrough vaccinated people is unknown. We studied a cohort 48 (aged 20 86 years) who received two doses messenger RNA (mRNA) vaccine and developed infection with 2 weeks 4 months later. Ab levels...
Human USP18 is an interferon (IFN)-stimulated gene product and a negative regulator of type I IFN (IFN-I) signaling. It also removes covalently linked ISG15 from proteins, in process called deISGylation. In turn, prevents being degraded by the proteasome. Autosomal recessive complete deficiency life-threatening infancy owing to uncontrolled IFN-I–mediated autoinflammation. We report three Moroccan siblings with autoinflammation mycobacterial disease who are homozygous for new variant....
Abstract Autoantibodies (auto-Abs) neutralizing type I interferons (IFNs) are found in the blood of at least 15% unvaccinated patients with life-threatening COVID-19 pneumonia. We report here presence auto-Abs IFNs bronchoalveolar lavage (BAL) 54 415 (13%) pneumonia tested. The individuals BAL included 45 (11%) against IFN-α2, 37 (9%) IFN-ω, IFN-α2 and/or ω, and five (1%) IFN-β, including three (0.7%) two (0.5%) IFN-β. Auto-Abs also neutralize other 12 subtypes IFN-α. Paired plasma samples...
We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients compound heterozygous three, all loss-of-expression loss-of-function. They abolish CCR2-agonist ligand...
Severe defects in human IFNγ immunity predispose individuals to both Bacillus Calmette-Guérin disease and tuberculosis, whereas milder only tuberculosis
Human inherited disorders of interferon-gamma (IFN-γ) immunity underlie severe mycobacterial diseases. We report X-linked recessive MCTS1 deficiency in men with disease from kindreds different ancestries (from China, Finland, Iran, and Saudi Arabia). Complete this translation re-initiation factor impairs the a subset proteins, including kinase JAK2 all cell types tested, T lymphocytes phagocytes. expression is sufficiently low to impair cellular responses interleukin-23 (IL-23) partially...
Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ∼10% patients hospitalized for TBE cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at onset disease, contrasting with only ∼1% TBE. These were found two eight who died none 13 silent infection. The odds...
Human inborn errors of thymic T cell tolerance underlie the production autoantibodies (auto-Abs) neutralizing type I IFNs, which predispose to severe viral diseases. We analyze 131 female patients with X-linked dominant incontinentia pigmenti (IP), heterozygous for loss-of-function (LOF) NEMO variants, from 99 kindreds in 10 countries. Forty-seven these (36%) have auto-Abs IFN-α and/or IFN-ω, a proportion 23 times higher than that age-matched controls. This remains stable age 6 years onward....
IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of IKK complex activating canonical alongside IKKβ. The absence IKKα causes fetal encasement syndrome humans, fatal utero, while an impaired IKKα-NIK interaction was reported a single patient combined immunodeficiency. Here, we describe compound heterozygous variants kinase domain female with hypogammaglobulinemia, recurrent lung infections, Hay–Wells syndrome-like features. We showed that both were...
Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, functional effects on circulating leukocytes remain unknown. Here, 284 patients, we IFN-I 19% of critical, 6% severe none moderate cases. Longitudinal profiling over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope transcriptome sequencing from 54 15 non-COVID-19...
Patients with autosomal recessive protein kinase C δ (PKCδ) deficiency suffer from childhood-onset autoimmunity, including systemic lupus erythematosus. They also recurrent infections that overlap those seen in patients chronic granulomatous disease (CGD), a caused by defects of the phagocyte NADPH oxidase and lack reactive oxygen species (ROS) production. We studied an international cohort 17 PKCδ-deficient found their EBV-B cells monocyte-derived phagocytes produced only small amounts ROS...