Isabelle Meyts

Isabelle Meyts
Universitair Ziekenhuis Leuven | UZ Leuven · Department of Pedriatrics

Doctor of Medicine, PhD

About

254
Publications
38,258
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
10,376
Citations
Citations since 2017
143 Research Items
8718 Citations
201720182019202020212022202305001,0001,5002,0002,500
201720182019202020212022202305001,0001,5002,0002,500
201720182019202020212022202305001,0001,5002,0002,500
201720182019202020212022202305001,0001,5002,0002,500

Publications

Publications (254)
Article
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 in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2′-5′-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase...
Article
Full-text available
Inborn and acquired deficits of type I interferon (IFN) immunity predispose to life-threatening COVID-19 pneumonia. We longitudinally profiled the B cell response to mRNA vaccination in SARS-CoV-2 naive patients with inherited TLR7, IRF7, or IFNAR1 deficiency, as well as young patients with autoantibodies neutralizing type I IFNs due to autoimmune...
Article
Inborn errors of immunity are a heterogenous group of monogenic immunological disorders caused by mutations in genes with critical roles in the development, maintenance or function of the immune system. The genetic basis is frequently a mutation in a gene with restricted expression and/or function in immune cells, leading to an immune disorder. Sev...
Article
Full-text available
Patients with hypomorphic mutations in RAG1 and RAG2 genes present as either Omenn syndrome or atypical combined immunodeficiency (CID) with a wide phenotypic range. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but data are scarce. We report on a worldwide cohort of 60 patients with hypomorphic RAG variants who underwent...
Article
Full-text available
Background Due to the absence of curative treatments for inborn errors of immunity (IEI), children born with IEI require long-term follow-up for disease manifestations and related complications that occur over the lifespan. Effective transition from pediatric to adult services is known to significantly improve adherence to treatment and long-term o...
Article
Full-text available
The International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) reports here the 2022 updated phenotypic classification, which accompanies and complements the most-recent genotypic classification. This phenotypic classification is aimed for clinicians at the bedside and focuses on clinical features...
Article
Purpose We aimed to investigate the molecular basis of a novel recognizable neurodevelopmental syndrome with scalp and enamel anomalies caused by truncating variants in the last exon of the gene FOSL2, encoding a subunit of the AP-1 complex. Methods Exome sequencing was used to identify genetic variants in all cases, recruited through Matchmaker e...
Article
Full-text available
Calcium signaling is essential for lymphocyte activation, with genetic disruptions of store-operated calcium (Ca2+) entry resulting in severe immunodeficiency. The inositol 1,4,5-trisphosphate receptor (IP3R), a homo- or heterotetramer of the IP3R1-3 isoforms, amplifies lymphocyte signaling by releasing Ca2+ from endoplasmic reticulum stores follow...
Article
Full-text available
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 neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6–73 yr with critical influenza pneumonia. Nine and...
Article
Full-text available
NFKB1 haploinsufficiengcy was first described in 2015 in three families with common variable immunodeficiency (CVID), presenting heterogeneously with symptoms of increased infectious susceptibility, skin lesions, malignant lymphoproliferation and autoimmunity. The described mutations all led to a rapid degradation of the mutant protein, resulting i...
Article
Encephalitis and encephalopathy in children represent a diagnostic challenge. We describe a patient with relapsing encephalitis in whom the differential diagnosis included acute disseminated encephalomyelitis (ADEM), human herpesvirus 6 (HHV-6) encephalitis, and hemophagocytic lymphohistiocytosis (HLH). Because of its rarity, HLH is often overlooke...
Article
Full-text available
Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneu...
Article
Full-text available
Deficiency of adenosine deaminase 2 (DADA2) is an inherited autosomal recessive disease characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages, end organ vasculitis), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow fai...
Article
Full-text available
Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients' fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical fe...
Article
Full-text available
We report the updated classification of inborn errors of immunity, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 55 novel monogenic gene defects, and 1 phenocopy due to autoantibodies, that have either been discovered since the previous update (publ...
Article
Introduction Les vaccins à ARN messagers ont joué un rôle majeur dans la lutte contre la pandémie de SARS-CoV-2 grâce à une excellente efficacité et sécurité clinique. Ces vaccins ont été développés suite à des années de recherche fondamentale, dont l’une des étapes cruciales a été de remplacer l’uridine de l’ARNm par de la 1-méthyl-pseudo-uridine...
Article
Full-text available
The complement system is an essential part of our innate immune system. Three enzymatic activation pathways are described, all converging into a common terminal pathway which causes lysis of the target cell. Late complement deficiencies (LCDs) are typically diagnosed in children or adolescents with invasive meningococcal disease (IMD). However, IMD...
Article
The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients present episodes of life-threatening necrosis, typically triggered by S. aureus infection. The disorder is p...
Article
Full-text available
Allogeneic hematopoietic stem cell transplantation (HSCT) is the gold standard curative therapy for infants and children with many inborn errors of immunity (IEI), but adolescents and adults with IEI are rarely referred for transplant. Lack of published HSCT outcome data outside small, single-center studies and perceived high risk of transplant-rel...
Article
Full-text available
Newborn or neonatal screening (NBS) is a population-based program aimed at the pre-symptomatic detection, shortly after birth, of serious treatable conditions. NBS thus permits the early delivery of appropriate therapy, preventing long-term disability or premature death. First introduced by Robert Guthrie in the 1960s to screen for phenylketonuria,...
Article
Full-text available
SARS-CoV-2 infection is benign in most individuals but, in ˜10% of cases, it triggers hypoxemic COVID-19 pneumonia, which becomes critical in ˜3% of cases. The ensuing risk of death (˜1%) doubles every five years from childhood onward and is ˜1.5 times greater in men than in women. What are the molecular and cellular determinants of critical COVID-...
Article
Full-text available
Newborn or neonatal screening (NBS) is a population-based program aimed at the pre-symptomatic detection, shortly after birth, of serious treatable conditions. NBS thus permits the early delivery of appropriate therapy, preventing long-term disability or premature death. Here we present ten elements for effective operation of NBS programmes in Eur...
Preprint
Full-text available
SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a s...
Article
Full-text available
Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with reg...
Article
Full-text available
SARS-CoV-2 infections display tremendous interindividual variability, ranging from asymptomatic infections to life-threatening disease. Inborn errors of, and autoantibodies directed against, type I interferons (IFNs) account for about 20% of critical COVID-19 cases among SARS-CoV-2-infected individuals. By contrast, the genetic and immunological de...
Article
Full-text available
Purpose Deficiency of adenosine deaminase type 2 (ADA2) (DADA2) is a rare inborn error of immunity caused by deleterious biallelic mutations in ADA2 . Clinical manifestations are diverse, ranging from severe vasculopathy with lacunar strokes to immunodeficiency with viral infections, hypogammaglobulinemia and bone marrow failure. Limited data are a...
Article
Full-text available
Purpose Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumo...
Article
Purpose of review: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused extreme concern for patients with inborn errors of immunity (IEIs). In the first 6 months of the pandemic, the case fatality rate among patients with IEIs resembled that of the general population (9%). This review aims at summarizing what we hav...
Article
The binary view of inborn errors of immunity classified as either autoinflammatory conditions or primary immunodeficiency in the strict sense, that is, increased susceptibility to infection is challenged by the description of recent inborn errors of immunity (IEI) triggers leading to activation and disruption of cell death pathways, play a major pa...
Article
Purpose of review: The severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV2)/COVID-19 pandemic has reminded us of the fundamental and nonredundant role played by the innate and adaptive immune systems in host defense against emerging pathogens. The study of rare 'experiments of nature' in the setting of inborn errors of immunity (IEI) caus...
Article
Full-text available
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (...
Article
Full-text available
Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (...
Article
Deficiency of human adenosine deaminase 2 (DADA2) is an auto-inflammatory inborn error of immunity caused by biallelic deleterious mutations in the gene encoding ADA2. The purpose of this article is to raise awareness among ophthalmologists and pediatricians to consider DADA2 as a possible diagnosis for patients with acute onset of diplopia. The au...
Preprint
Full-text available
Calcium signaling is essential for lymphocyte activation, with genetic disruptions resulting in severe immunodeficiency. The inositol 1,4,5-trisphosphate receptor (IP3R), formed from homo- or hetero-tetramers of the IP3R isoforms 1-3, amplifies lymphocyte signaling by releasing Ca2+ from ER stores into the cytosol following antigen-stimulation. Whi...
Article
Full-text available
Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically heterogenous pediatric inflammatory condition for which weak associations have been found with a myriad of vira...
Article
Chronic Granulomatous Disease (CGD) is an immunodeficiency disorder affecting about 1 in 250,000 individuals. CGD patients suffer from severe bacterial and fungal infections. The disease is caused by a lack of superoxide production by the leukocyte enzyme NADPH oxidase. Superoxide and subsequently formed other reactive oxygen species (ROS) are inst...
Article
Discussion on the increase in nonclassical monocytes in patients with DADA2 as shown by scRNA seq; these pro inflammatory cells also show increased TNFR2, type I, and type II IFN pathway gene expression.
Article
Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either the PKD1 or PKD2 gene. While kidney failure typically occurs in adulthood, the disease starts in utero. The best change of preserving renal function long term might be the use of agents with few side effects as early as possible. For this appro...
Article
Background and Aims Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenetic inherited kidney disease, has been reported to be associated with distinct cytopenias. The pathophysiological mechanism behind this association and its clinical implications are unknown. Sparse and conflicting data have suggested a tendency to grea...
Article
Activating PI3Kδ mutations: clinical and biochemical presentation of treatable primary immune deficiencies The field of primary immune deficiencies is expanding rapidly. Recently, gain-of-function (GOF) mutations in the phosphoinositide 3 kinase (PI3K) CD and PI3KR1 genes have been reported to cause a clinical syndrome referred to as activated PI3K...
Article
Full-text available
Type I interferons (IFNs) are so‐named because they interfere with viral infection in vertebrate cells. The study of cellular responses to type I IFNs led to the discovery of the JAK‐STAT signaling pathway, which also governs the response to other cytokine families. We review here the outcome of viral infections in mice and humans with engineered a...
Article
Primary antibodydeficiencies (PAD) constitute the majority of all primary immunodeficiency diseases (PID) also termed in born errors of immunity (IEI). This category (PAD) representsaround 52% of all IEI and the proportion overall is still greater given that antibody deficiency is a component of other groups including combined and severe combined i...
Article
Full-text available
The most recent updated classification of inborn errors of immunity/primary immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee, was published in January 2020. Within days of completing this report, it was already out of date, evidenced by the frequent publication of genetic variants proposed to cause...
Article
Full-text available
Introduction Autosomal dominant polycystic kidney disease (ADPKD) causes kidney failure typically in adulthood, but the disease starts in utero. Copeptin, epidermal growth factor (EGF) and monocyte chemoattractant protein-1 (MCP-1) are associated with severity and hold prognostic value in adults but remain unstudied in the early disease stage. Kidn...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
Systemic autoinflammatory disorders comprise an expanding group of rare conditions. They are mediated by dysfunction of the innate immune system and share a core of phenotypic manifestations including recurrent attacks of fever, cutaneous signs, chest or abdominal pain, lymphadenopathy, vasculopathy, and musculoskeletal symptoms. Diagnosis is often...
Article
Autosomal dominant polycystic kidney disease (ADPKD) is associated with distinct cytopenias in observational studies; the most consistent and strongest association is seen with alternations in the lymphocytic lineages. Although the underlying mechanism of these associations is unclear, it has been hypothesized to be secondary to sequestration of wh...
Article
Full-text available
Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans. B cell responses to these "common cold" viruses remain incompletely understood. Here we report a comprehensive analysis of CoV-specific antibody repertoires in 231 children and 1168 adults using phage-immunoprecipitation sequencing. Seroprev...
Article
Full-text available
Ras-associated autoimmune leukoproliferative disorder (RALD) is a clinical entity initially identified in patients evaluated for an autoimmune lymphoproliferative syndrome (ALPS)-like phenotype. It remains a matter of debate whether RALD is a chronic and benign lymphoproliferative disorder or a pre-malignant condition. We report the case of a 7-yea...
Article
Full-text available
STING-associated vasculopathy with onset in infancy (SAVI) is an autosomal dominant disorder due to gain-of-function mutations in STING1, also known as TMEM173, encoding for STING. It was reported as a vasculopathy of infancy. However, since its description a wider spectrum of associated manifestations and disease-onset has been observed. We report...
Article
Full-text available
Abstract Background There is uncertainty about the impact of SARS-CoV-2 infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe COVID-19. This is relevant not only for these patients but also the general population, as studies of IEIs can unveil key requirements for host defense. Objective De...
Article
Full-text available
The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflamm...