Isabelle Melki

Isabelle Melki
Institut Imagine · Laboratory of neurogenetics and neuroinflammation

MD

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136
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Publications

Publications (136)
Preprint
Full-text available
This study was conducted to identify the contribution of myositis-specific antibodies (MSAs) on the correlation between type I interferon (IFN-I) plasma levels and disease activity in juvenile dermatomyositis (JDM) patients. We prospectively obtained 198 samples from 49 JDM patients. Autoantibody levels were determined for all patients. Muscle acti...
Preprint
NLRP3-associated autoinflammatory disease (NLRP3-AID or CAPS) is an heterogenous group of monogenic autoinflammations associated with NLRP3 gain-of-function mutations. The poor functional characterization of most NLRP3 variants is a barrier to diagnosis although patients can be efficiently treated with anti-IL-1 approaches. In addition, while NLRP3...
Article
Full-text available
Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases with probably differential underlying physiopathology. Despite the revolutionary era of biologics, some patients remain difficult to treat because of disease severity, drug adverse events, drug allergy or association with severe comorbidities, i.e., uveitis, interstitial lung...
Article
Full-text available
An European Alliance of Associations for Rheumatology task force recently recommended specific points to consider for exploring type I interferon pathway in patients, highlighting the lack of analytical assays validated for clinical routine. We report here the French experience on a type I interferon pathway assay that has been set up and used rout...
Article
Background Dermatomyosis is an autoimmune disease that can present in children, adolescents (juvenile dermatomyosis JDM), and adults (adult dermatomyositis DM). The pathological hallmarks of DM are similar between JDM and adult DM, including skin rashes and proximal muscle weakness, however, the manifestations and prevalence of associated autoantib...
Article
Background Familial Mediterranean fever (FMF) is the most common autoinflammatory disease worldwide. It affects mainly population from Mediterranean origin and is associated with MEFV exon 10 mutations. FMF is characterized by short and recurrent attacks of fever, abdominal or thoracic pain that lasts less than three days [1]. Several studies repor...
Article
Objectives: Hip involvement remains a predictor of severe juvenile idiopathic arthritis (JIA) course and carries a high risk of disability. This study aims to determine the factors of poor prognosis of hip involvement in patients with JIA and to assess the treatment response. Methods: This is a multicenter observational cohort study. Patients we...
Article
Dear Editor, Data on osteonecrosis (ON) in JDM are limited [1]. It is usually considered as the result of corticosteroid therapy. Herein, we report a case series of five patients among a cohort of 71 patients with JDM who developed severe ON. All of them had anti-MDA5 positive JDM, which suggests that MDA5-positive JDM patients may have predisposin...
Article
Full-text available
Introduction Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic autoimmune disease affecting multiple organs. Ranging from minor features, such as headache or mild cognitive impairment, to serious and life-threatening presentations, j-neuropsychiatric SLE (j-NPSLE) is a therapeutic challenge. Thus, the diagnosis of NPSLE remains diffic...
Article
Full-text available
Background Early identification of high-risk patients is essential to stratify treatment algorithms of Kawasaki disease (KD) and to appropriately select patients at risk for complicated disease who would benefit from intensified first-line treatment. Several scores have been developed and validated in Asian populations but have shown low sensitivit...
Article
Full-text available
Objectives: To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases. Methods: The TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the regi...
Article
Aim To describe the management of home oxygen therapy for infants with acute bronchiolitis through a home care network: Hospital at Home (HAH). Methods A retrospective observational study was carried out during two consecutive winters from 2012 to 2014. Results A total of 141 patients were eligible for home oxygen therapy, and 54 were discharged...
Article
Résumé Les vascularites primitives de l’enfant sont des maladies inflammatoires rares touchant les vaisseaux sanguins et pouvant se compliquer d’ischémie, voire de nécrose de certains organes. Elles constituent un véritable défi diagnostique et thérapeutique pour les pédiatres. À l’échelle mondiale, les vascularites les plus fréquentes de l’enfant...
Article
Full-text available
Background: Patients with inflammatory rheumatic and musculoskeletal diseases (iRMD) receiving mycophenolic acid (MPA) may have a less favourable outcome from COVID-19 infection. Our aim was to investigate whether MPA treatment is associated with severe infection and/or death. Methods: IRMD patients with and without MPA treatment with highly sus...
Article
Full-text available
Objective: To highlight the safety and efficacy of Tumor Necrosis Factor inhibitors (anti-TNF) in inflammatory choroidal neovascularization (CNV) in the pediatric population. Design: Retrospective case series. Participants: Three patients, < 16 years old with uveitic inflammatory CNV. Methods: Patients received systemic steroids, methotrexat...
Article
Introduction L’association entre une vascularite des gros vaisseaux telle que l’artérite de Takayasu (AT) ou l’artérite à cellules géantes (ACG) et une maladie inflammatoire chronique de l’intestin (MICI), principalement la maladie de Crohn (MC) ou la rectocolite hémorragique (RCH), est rare. Le but de notre étude était de décrire les caractéristiq...
Article
Full-text available
Introduction La myocardite fulminante associée aux auto-anticorps anti-ARN polymérases III (ARNpol3) est une entité récemment décrit associant la survenue de myocardites aiguës fulminantes et/ou de péricardites sévères, principalement d’origine grippale et volontiers récidivantes, chez des patients présentant des ARNpol3 sans sclérodermie systémiqu...
Article
Background The low prevalence of systemic autoimmune diseases and the diversity of their clinical manifestations make complex to conduct randomised clinical trials to assess the potential efficacy of targeted treatments. Objectives To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory autoimmune diseases. M...
Article
Résumé Les maladies auto-inflammatoires liées à des mutations du gène RIPK1 ont été décrites récemment. Il existe deux phénotypes cliniques distincts en fonction du type et de la localisation des variants. Lorsque la mutation est récessive induisant une perte de fonction, les patients présentent un tableau mixte de déficit immunitaire avec des infe...
Article
Background Pediatric Inflammatory Multisystemic Syndrome associated to SARS-CoV2 (PIMS) happens 4 to 6 weeks after SARS-CoV2 infection ¹⁻² . Its early diagnostic recognition as well as its early management is important to avoid cardiac complications related to this pathology. Objectives To highlight a frequent symptom in PIMS and improve its thera...
Article
Objectives Some adults with rheumatic and musculoskeletal diseases (RMDs) are at increased risk of COVID-19-related death. Excluding post-COVID-19 multisystem inflammatory syndrome of children, children and young people (CYP) are overall less prone to severe COVID-19 and most experience a mild or asymptomatic course. However, it is unknown if CYP w...
Article
Case Report A 6-month-old girl with mild developmental delay and hepatosplenomegaly was referred to our reference center for investigation of a possible inborn error of metabolism. She exhibited eczematous skin lesions on the arms and legs, which were treated with corticosteroids. Physical examination confirmed liver and spleen enlargement associat...
Article
Introduction La population pédiatrique est sous-représentée dans la pandémie actuelle, en termes de nombre de cas et de sévérité. De surcroît le risque évolutif de l’infection au SARS-CoV-2 dans cette population, en cas de maladies inflammatoires sous traitements immuno-modulateurs, est peu connu. Cette population de jeunes patients immuno-déprimés...
Article
Full-text available
Significance Life-threatening COVID-19 pneumonia can be caused by rare inborn errors of type I interferon (IFN) immunity, or by autoantibodies neutralizing IFN-α2 or IFN-ω. In 2018, we reported a girl with critical influenza pneumonia due to inherited IRF9 deficiency, a component of the ISGF-3 transcription factor. We report the course of COVID-19...
Article
Full-text available
Mevalonate kinase deficiency should be considered in patients with severe very-early-onset inflammatory bowel disease (IBD), especially in patients with a history of recurrent or chronic fever, peritoneal adhesions, and atypical IBD pathology. Anti-interleukin-1 therapy may be efficacious in these patients with monogenic very-early-onset IBD.
Article
Background SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. Methods To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection...
Article
Aicardi-Goutières syndrome (AGS) is a rare genetic neuroinflammatory disorder caused by abnormal upregulation of type 1 interferon signalling. Opsoclonus-myoclonus syndrome is a rare autoimmune phenotype demonstrating a disturbance in the humoral immune response mostly seen in the context of paraneoplastic or postinfectious states, although its pat...
Conference Paper
Full-text available
Background It remains unknown whether children and young people with rheumatic and musculoskeletal diseases (RMD) who acquire COVID-19 infection have a more severe COVID-19 course, due to either underlying disease or immunosuppressive treatments. Objectives To describe outcomes among children and young people with underlying RMD who acquire COVID-...
Article
Introduction L’épidémie actuelle de maladie à coronavirus 2019 (COVID-19) peut toucher tous les patients atteints de maladies auto-immunes et systémiques. Les patients souffrant d’un lupus systémique (LS) ont des facteurs de risque de développer des formes sévères de COVID-19 en raison des comorbidités fréquemment associées au LS (insuffisance réna...
Article
Introduction L’effet des antipaludéens de synthèse sur les infections virales est étudié depuis plusieurs années, y compris l’hypothèse d’un effet sur le SARS [1]. L’efficacité in vitro de la chloroquine contre le SARS-CoV-2 a été décrite [2], ainsi que la supériorité potentielle de l’hydroxycholoroquine. De nombreuses études in vivo ont été menées...
Article
Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. We aim to provide a quantitative description of the natural history of the condition by describing 19 affected individuals and...
Article
Full-text available
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been characterized by high transmission rates and high mortality in adults with predisposing factors, including age > 70 years, obesity, diabetes, systemic hypertension and other underlying diseases. During the second week of viral pneumonia, acute respiratory distress sy...
Article
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Whilst upregulation of type I interferon (IFN) signaling is common across the type I interferonopathies (T1Is), central nervous system (CNS) involvement varies between these disorders, the basis of which remains unclear. We collected cerebrospinal fluid (CSF) and serum from patients with Aicardi-Goutières syndrome (AGS), STING-associated vasculopat...
Article
Full-text available
Background: Hydroxychloroquine (HCQ) is an antimalarial agent given to patients with systemic lupus erythematosus (SLE) as first-line therapy. It alleviates childhood-onset systemic lupus erythematosus cSLE skin and musculoskeletal disease, decreasing disease activity and flares. HCQ concentration-effect relationships in children remains unknown....
Article
RÉSUMÉ La pandémie due à SARS-CoV-2 est caractérisée par une haute contagiosité et une mortalité élevée chez les adultes à risque (âge supérieur à 65 ans, obésité, diabète, hypertension). Au décours d’une pneumonie virale, survient parfois une phase hyper-inflammatoire compliquée d’une défaillance multi-viscérale dont un Syndrome de Détresse Respir...
Preprint
SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe fo...
Article
Full-text available
Juvenile idiopathic arthritis is the most common chronic rheumatic disease in children, and its etiology remains poorly understood. Here, we explored four families with early-onset arthritis carrying homozygous loss-of-expression mutations in LACC1. To understand the link between LACC1 and inflammation, we performed a functional study of LACC1 in h...
Article
Full-text available
Objective: To evaluate the efficacy and safety of JAK inhibitors (JAKi) in juvenile dermatomyositis (JDM). Methods: We conducted a single-center retrospective study of patients with JDM treated by JAKi with a follow-up of at least 6 months. Proportion of clinically inactive disease (CID) within six months of JAKi initiation was evaluated using P...
Article
Full-text available
Behçet’s disease (BD) is a systemic variable vessel vasculitis that involves the skin, mucosa, joints, eyes, arteries, veins, nervous system and gastrointestinal system, presenting with remissions and exacerbations. It is a multifactorial disease, and several triggering factors including oral cavity infections and viruses may induce inflammatory at...
Article
Full-text available
Objectives Juvenile idiopathic inflammatory/immune myopathies (JIIM) constitute a highly heterogeneous group with diagnostic difficulties and prognostic uncertainties. Circulating myositis‐specific autoantibodies (MSAs) were first recognized as reliable tools for patient sub‐stratification. Considering the key role of type 1 interferon (IFN‐I) up‐r...
Article
Introduction Même rare, la dermatomyosite juvénile (DMJ) est la myopathie inflammatoire la plus fréquente chez l’enfant. Les anticorps spécifiques des myosites (ASM) s’excluent mutuellement et sont associés à des tableaux cliniques caractérisés chez l’adulte, moins décrits chez l’enfant. Notre objectif était d’identifier une éventuelle corrélation...
Article
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Background Gain-of-function mutations in STING1 underlie a type I interferonopathy termed SAVI (STING-associated vasculopathy with onset in infancy). This severe disease is variably characterized by early-onset systemic inflammation, skin vasculopathy, and interstitial lung disease (ILD). Objective To describe a cohort of patients with SAVI. Meth...
Article
Tumor necrosis factor-α (TNF-α) inhibitors have resulted in significant progress in the treatment of chronic inflammatory diseases. However, these therapies can lead to paradoxical immune-mediated inflammatory diseases with unknown physiopathology. For the first time, we report 3 cases of paradoxical chronic recurrent multifocal osteomyelitis after...
Article
Full-text available
Purpose of the review: Type I interferonopathies are monogenic autoinflammatory diseases induced by constitutive activation of type I interferon. Here, we provide an overview of these diseases and describe underlying molecular pathways, related phenotypes, suggestive clinical signs and investigations for helping diagnosis process and therapeutic m...
Article
Full-text available
Background Kawasaki disease is an acute febrile systemic childhood vasculitis, which is suspected to be triggered by respiratory viral infections. We aimed to examine whether the ongoing COVID-19 epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with an increase in the incidence of Kawasaki disease. Me...
Article
Full-text available
Background Current data suggest that COVID-19 is less frequent in children, with a milder course. However, over the past weeks, an increase in the number of children presenting to hospitals in the greater Paris region with a phenotype resembling Kawasaki disease (KD) has led to an alert by the French national health authorities. Methods Multicentr...
Article
Objectives To assess the incidence rate and type of serious adverse events (SAE) in children with rheumatic inflammatory diseases treated with the interleukin 6 blocker tocilizumab (TCZ). Methods A retrospective review of all consecutive patients diagnosed with an inflammatory rheumatic disease and receiving at least one dose of TCZ was performed...
Article
Objective Acne fulminans (AF) is a rare, explosive systemic form of acne. Chronic non-bacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO) is a primarily pediatric autoinflammatory disorder characterized by sterile osteolytic bone lesions. Concomitant occurrence of CNO/CRMO and AF is very rare and little is known about...
Article
Background Systemic lupus erythematosus (SLE) is a rare immunological disorder and genetic factors are considered important in its causation. Monogenic lupus has been associated with around 30 genotypes in humans and 60 in mice, while genome-wide association studies have identified more than 90 risk loci. We aimed to analyse the contribution of rar...
Article
Full-text available
In the original article, the CTRL values from Figure 1A were incorrect. The figure has now been replaced. In addition, in comparison to controls (median 0.0056 fg/ml [0.0004-45.05 fg/ml]; P 0.0025) in the text was replaced by in comparison to controls (median 0.65 fg/ml [0.65-45.05 fg/ml]; P 0.0025). © 2019 The Author(s) 2019. Published by Oxford U...
Article
BACKGROUND Systemic lupus erythematosus (SLE) is a rare immunological disorder and genetic factors are considered important in its causation. Monogenic lupus has been associated with around 30 genotypes in humans and 60 in mice, while genome-wide association studies have identified more than 90 risk loci. We aimed to analyse the contribution of rar...
Article
Full-text available
Background: NLRP3-associated autoinflammatory diseases (NLRP3-AIDs) include conditions of various severities, due to germline or somatic mosaic NLRP3 mutations. Objective: To identify mosaic-specific versus germline-specific NLRP3 mutations' characteristics, we reinterpreted all the mutations reported in NLRP3-AIDs and performed an in-depth stud...
Article
Full-text available
Objectives: JDM and juvenile overlap myositis represent heterogeneous subtypes of juvenile idiopathic inflammatory myopathy (JIIM). Chronic evolution can occur in up to 60% of cases, and morbidity/mortality is substantial. We aimed to describe the clinical, biological, histological and type I IFN status in JIIM associated with anti-melanoma differ...
Article
Background: Blau syndrome (BS) is a rare monogenic autoinflammatory disease caused by NOD2 mutations. BS classically presents in early childhood as a triad of granulomatous polyarthritis, uveitis and skin involvement. Joint and ocular involvement have been characterized by several cohort studies but only very little data is available on skin lesio...
Article
Full-text available
We read with interest the study of Mathian et al (1), suggesting that direct serum IFNα determination with a highly sensitive assay might be useful for disease activity monitoring in systemic lupus erythematosus (SLE). More generally, the identification of reactive biomarkers is highly desirable in many disease states, including idiopathic inflamma...
Article
Introduction Les auto-anticorps anti-ARN polymérases III (ARNpol3) sont des anticorps spécifiques de la sclérodermie systémique, principalement associés à des formes viscérales graves. Nous avons récemment identifié la présence d’ARNpol3 chez des patients présentant des myopéricardites virales aiguës sévères, en l’absence de sclérodermie systémique...
Conference Paper
Background Juvenile dermatomyositis (JDM) is a rare heterogeneous autoimmune disease. The identification of myositis specific antibodies (MSAs) has allowed the characterization of subgroups of JDM patients who each have specific phenotypes. Antibody (Ab) against transcriptional intermediary factor-1-γ (TIF-1-γ or p155/140) is the most common MSA in...