Publications de Alessandro Borghesi

Human type I interferons protect Vero E6 and ARPE-19 cells against West Nile virus and are neutralized by pathogenic autoantibodies

Auto-antibodies (auto-Abs) that neutralize type I interferons (IFNs) have been implicated in severe viral infections, including ~ 40% of cases of West Nile virus (WNV) neuroinvasive disease (WNND). Developing robust in vitro models to evaluate the protecti ...

2025

Life-threatening infections in human newborns: Reconciling age-specific vulnerability and interindividual variability

Alessandro Borghesi

In humans, the interindividual variability of clinical outcome following exposure to a microorganism is immense, ranging from silent infection to life-threatening disease. Age-specific immune responses partially account for the high incidence of infection ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2024

Tuberculosis in otherwise healthy adults with inherited TNF deficiency

Alessandro Borghesi

Severe defects in human IFN gamma immunity predispose individuals to both Bacillus Calmette-Gu & eacute;rin disease and tuberculosis, whereas milder defects predispose only to tuberculosis1. Here we report two adults with recurrent pulmonary tuberculosis w ...

NATURE PORTFOLIO2024

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

Alessandro Borghesi

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) (similar to 40% of patients) and tick-borne encephalitis (TBE, due ...

ROCKEFELLER UNIV PRESS2024

Autoantibodies neutralizing type I IFNs underlie severe tick-borne encephalitis in ∼10% of patients

Alessandro Borghesi

Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (

ROCKEFELLER UNIV PRESS2024

Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency

Jacques Fellay, Christian Axel Wandall Thorball, Alessandro Borghesi, Qian Zhang, Peng Zhang, Yu Zhang

Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs) 1,2 , conferring a predisposition to life-threatening COVID-19 pneumonia 3 . ...

Nature Portfolio2023

Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in & SIM;40% of patients

Jacques Fellay, Alessandro Borghesi

Gervais et al. show that auto-Abs neutralizing type I IFNs and pre-existing infection underlie & SIM;40% of cases of West Nile virus (WNV) encephalitis. Blood and cerebrospinal fluid auto-Abs neutralize the protective activity of type I IFNs against WNV in ...

ROCKEFELLER UNIV PRESS2023

Neonatal Manifestations of Chronic Granulomatous Disease: MAS/HLH and Necrotizing Pneumonia as Unusual Phenotypes and Review of the Literature

Alessandro Borghesi

Chronic granulomatous disease (CGD) is a rare inborn error of immunity (IEI), characterized by a deficient phagocyte killing due to the inability of NADPH oxidase to produce reactive oxygen species in the phagosome. Patients with CGD suffer from severe and ...

SPRINGER/PLENUM PUBLISHERS2022

PUS3-related disorder: Report of a novel patient and delineation of the phenotypic spectrum

Alessandro Borghesi

PUS3 encodes the pseudouridylate synthase 3, an enzyme catalyzing the formation of tRNA pseudouridine, which plays a critical role in tRNA structure, function, and stability. Biallelic pathogenic variants of PUS3 have been previously associated with severe ...

WILEY2022

Autoantibodies against type I IFNs in patients with Ph-negative myeloproliferative neoplasms

Alessandro Borghesi

AMER SOC HEMATOLOGY2022

How to: Diagnose inborn errors of intrinsic and innate immunity to viral, bacterial, mycobacterial, and fungal infections

Alessandro Borghesi

Background: Inborn errors of intrinsic and innate immunity constitute the focus of a growing research field that investigates the molecular mechanisms underlying susceptibility to infections previously not considered part of the spectrum of inborn errors o ...

ELSEVIER SCI LTD2022

Neonatal-Onset Familial Mediterranean Fever in an Infant with Human Parainfluenza Virus-4 Infection

Alessandro Borghesi

Unusual, severe infections or inflammatory episodes in newborns and infants are largely unexplained and often attributed to immature immune responses. Inborn errors of immunity (IEI) are increasingly recognized as the etiology of life-threatening inflammat ...

KARGER2021

Immunological lessons from genome-wide association studies of infections

Jacques Fellay, Christian Axel Wandall Thorball, Alessandro Borghesi

Over the past few years, genome-wide association studies (GWAS) have been increasingly applied to identify host genetic factors influencing clinical and laboratory traits related to immunity and infection, and to understand the interplay between the host a ...

CURRENT BIOLOGY LTD2021

Susceptibility to infection in early life: a growing role for human genetics

Jacques Fellay, Alessandro Borghesi

The unique vulnerability to infection of newborns and young infants is generally explained by a constellation of differences between early-life immune responses and immune responses at later ages, often referred to as neonatal immune immaturity. This devel ...

SPRINGER2020

Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment

Jacques Fellay, Christian Axel Wandall Thorball, Alessandro Borghesi

Background: The primary hurdle for the eradication of HIV-1 is the establishment of a latent viral reservoir early after primary infection. Here, we investigated the potential influence of human genetic variation on the HIV-1 reservoir size and its decay r ...

LIPPINCOTT WILLIAMS & WILKINS2020

Whole-exome Sequencing for the Identification of Rare Variants in Primary Immunodeficiency Genes in Children With Sepsis: A Prospective, Population-based Cohort Study

Samira Asgari, Jacques Fellay, Nimisha Chaturvedi, Christian Axel Wandall Thorball, Alessandro Borghesi

Background. The role of primary immunodeficiencies (PID) in susceptibility to sepsis remains unknown. It is unclear whether children with sepsis benefit from genetic investigations. We hypothesized that sepsis may represent the first manifestation of under ...

OXFORD UNIV PRESS INC2020

Blacklisting variants common in private cohorts but not in public databases optimizes human exome analysis

Jacques Fellay, Alessandro Borghesi

Computational analyses of human patient exomes aim to filter out as many nonpathogenic genetic variants (NPVs) as possible, without removing the true disease-causing mutations. This involves comparing the patient's exome with public databases to remove rep ...

National Academy of Sciences2019

Determinants of HIV-1 reservoir size and long-term dynamics during suppressive ART

Jacques Fellay, Christian Axel Wandall Thorball, Alessandro Borghesi

The HIV-1 reservoir is the major hurdle to a cure. We here evaluate viral and host characteristics associated with reservoir size and long-term dynamics in 1,057 individuals on suppressive antiretroviral therapy for a median of 5.4 years. At the population ...

Springer2019

Neonatal Group B Streptococcal Disease in Otherwise Healthy Infants: Failure of Specific Neonatal Immune Responses

Jacques Fellay, Alessandro Borghesi

Only a small proportion of newborn infants exposed to a pathogenic microorganism develop overt infection. Susceptibility to infection in preterm infants and infants with known comorbidities has a likely multifactorial origin and can be often attributed to ...

Frontiers Media Sa2017

Familial segregation of group B streptococcal infection in a consanguineous kindred

Jacques Fellay, Alessandro Borghesi

Two cases of neonatal group B streptococcal (GBS) infection occurring in a large consanguineous kindred are described. The observation suggests that susceptibility to isolated GBS disease in this family may have been the result of an inborn error of immuni ...

Elsevier Sci Ltd2016