Autoantibodies against type I IFNs in patients with life-threatening COVID-19

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 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Diffuse-interface modelling of multicomponent diffusion and phase separation in the U-O-Zr ternary system

International audienceThe ternary mixture of uranium, zirconium and oxygen is investigated as a minimal model for corium, the mixture that forms after the meltdown of a nuclear reactor. Like corium, U-Zr-O exhibits a liquidliquid phase separation between a metal-rich and an oxyde-rich phase at high temperatures. A CALPHAD database built on an associate model is used to set up a ternary Cahn-Hilliard model, which can describe two-phase patterns in U-Zr-O and may be coupled to the Navier-Stokes equations for hydrodynamic flows. The interface structure and properties, which depend on the choice on the gradient energy coefficients in the free-energy functional, are studied in detail. It is found that interface adsorption is generally present, but that its magnitude is small, such that the model remains a robust and useful tool for future simulations of corium pool stratification dynamics

Comparative genetic analysis of inflammatory bowel disease and type 1 diabetes implicates multiple loci with opposite effects

Inflammatory bowel disease, including Crohn's disease (CD) and ulcerative colitis (UC), and type 1 diabetes (T1D) are autoimmune diseases that may share common susceptibility pathways. We examined known susceptibility loci for these diseases in a cohort of 1689 CD cases, 777 UC cases, 989 T1D cases and 6197 shared control subjects of European ancestry, who were genotyped by the Illumina HumanHap550 SNP arrays. We identified multiple previously unreported or unconfirmed disease associations, including known CD loci (ICOSLG and TNFSF15) and T1D loci (TNFAIP3) that confer UC risk, known UC loci (HERC2 and IL26) that confer T1D risk and known UC loci (IL10 and CCNY) that confer CD risk. Additionally, we show that T1D risk alleles residing at the PTPN22, IL27, IL18RAP and IL10 loci protect against CD. Furthermore, the strongest risk alleles for T1D within the major histocompatibility complex (MHC) confer strong protection against CD and UC; however, given the multi-allelic nature of the MHC haplotypes, sequencing of the MHC locus will be required to interpret this observation. These results extend our current knowledge on genetic variants that predispose to autoimmunity, and suggest that many loci involved in autoimmunity may be under a balancing selection due to antagonistic pleiotropic effect. Our analysis implies that variants with opposite effects on different diseases may facilitate the maintenance of common susceptibility alleles in human populations, making autoimmune diseases especially amenable to genetic dissection by genome-wide association studies

AIRWAYS-ICPs (European Innovation Partnership on Active and Healthy Ageing) from concept to implementation

Chronic respiratory diseases (CRDs) are major non-communicable diseases (NCDs) that induce a significant burden. Asthma often occurs along the life cycle from early childhood, affecting 30 million children and adults under 45 years of age in Europe. Chronic obstructive pulmonary disease (COPD) has an estimated annual death rate of over 3 million people globally. The annual direct and indirect costs in the 28 European Union (EU) countries due to COPD or asthma are estimated at 48 billion euros and 34 billion euros respectively. Rhinitis occurs in over 100 million people in Europe, and indirect costs are enormous [4]. Asthma is a common risk factor for COPD. CRDs impact ageing and should be prevented, recognised and managed across the life cycle to promote active and healthy ageing (AHA). There is an urgent need to act globally