Publications by authors named "Alexandre Belot"
Article Synopsis
- Familial Mediterranean fever (FMF) is a genetic condition marked by inflammation episodes, usually treated with colchicine to prevent complications like amyloid A amyloidosis, but its necessity for heterozygous patients is debated.* -
- A study analyzed 747 FMF patients' demographic and inflammatory biomarker data, revealing that heterozygous patients generally exhibited lower inflammatory markers compared to those with more severe genetic variants.* -
- The findings suggest that certain biomarkers (S100A8/A9 and S100A12) can indicate disease activity, and some heterozygous patients may be eligible to safely stop colchicine treatment.*
Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.
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- - C1q deficiency is a rare immune disorder that increases the risk of infections and autoimmune diseases similar to systemic lupus erythematosus (SLE), often leading to various health complications.
- - An international study involving 18 patients evaluated the outcomes of hematopoietic stem cell transplantation (HSCT) for C1q deficiency, showing a 71% overall survival rate and improvement in autoimmune symptoms for most patients.
- - The study highlights that patients with severe autoimmune symptoms have poorer survival rates, and specific antibodies were linked to different organ involvements, emphasizing the need for careful patient selection and risk assessment for HSCT as a treatment option.
Article Synopsis
- * It typically affects Caucasians equally across genders and can also be associated with other autoimmune diseases like polyarteritis nodosa.
- * While ocular symptoms often have a good prognosis with potential recovery of vision, cochleo-vestibular issues can lead to serious and irreversible hearing loss, and treatment options are not well-established due to the condition's rarity.
Objectives: A new form of systemic juvenile idiopathic arthritis (SJIA) with associated lung disease (SJIA-LD) has recently been described. Multiple lines of treatment have failed to yield satisfactory results for this disorder. JAK inhibitors (JAKis) have recently been approved for the treatment of JIA, but clinical evidence of their efficacy in SJIA-LD is still weak.
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- Some experts and patients worked together to create a set of important data to help study childhood lupus, a disease that affects children.
- They made two datasets: a Core Dataset with 46 necessary items and an Expanded Dataset with 26 extra items, to help gather more information.
- This new information will help researchers around the world study childhood lupus better by using the same important facts and details.
Unlabelled: Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are considered the same disease, but a common approach for diagnosis and management is still missing.
Methods: In May 2022, EULAR and PReS endorsed a proposal for a joint task force (TF) to develop recommendations for the diagnosis and management of sJIA and AOSD. The TF agreed during a first meeting to address four topics: similarity between sJIA and AOSD, diagnostic biomarkers, therapeutic targets and strategies and complications including macrophage activation syndrome (MAS).
Article Synopsis
- A study on European FMF patients found that 20% experienced a diagnostic delay of over 10 years, with affected individuals being significantly older.
- Women were more likely to have this diagnostic delay compared to men, and specific symptoms like erysipelas-like erythema were more prevalent in delayed diagnosis cases.
- Delayed-diagnosis patients also had higher occurrences of AA amyloidosis and were more frequently treated with biotherapy, indicating more severe disease consequences.
Because Systemic Lupus Erythematosus (SLE) is a rare disease, and due to the significant prognostic impact of early management, a diagnosis confirmed by a physician with experience in SLE is recommended, for example from an expert center. Once the diagnosis is confirmed, existing manifestations should be identified in particular, renal involvement by an assessment of proteinuria, disease activity and severity should be determined, potential complications anticipated, associated diseases searched for, and the patient's socioprofessional and family context noted. Therapeutic management of SLE includes patient education on recognizing symptoms, understanding disease progression as well as when they should seek medical advice.
View Article and Find Full Text PDFObjective: The objective is to explore the journey to diagnosis and referral pathway from the onset of symptoms to the initial assessments at paediatric rheumatology (PR) centres, based on the experience of children with juvenile idiopathic arthritis (JIA) and their parents.
Design: We conducted a qualitative study with semistructured interviews. Our qualitative and phenomenological procedure applied interpretative phenomenological analysis.
An exome sequencing strategy employed to identify pathogenic variants in patients with pediatric-onset systemic lupus or Evans syndrome resulted in the discovery of six novel monoallelic mutations in PTPN2. PTPN2 is a phosphatase that acts as an essential negative regulator of the JAK/STAT pathways. All mutations led to a loss of PTPN2 regulatory function as evidenced by in vitro assays and by hyperproliferation of patients' T cells.
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- - Systemic lupus erythematosus (SLE) is a complex autoimmune disease with various signs and causes, but recent discoveries of rare monogenic forms have identified specific genetic defects that contribute to its development.
- - These monogenic forms can be categorized by different signaling pathways involved in immune responses, such as those related to apoptotic cell clearance and type I interferon signaling, providing a deeper understanding of the disease's mechanisms.
- - In children, where these genetic forms are more common, genetic testing is crucial, offering about a 10% diagnostic success rate and leading to more targeted and effective treatment options based on individual genetic profiles.
Article Synopsis
- DNA-PKcs is crucial for repairing DNA double-strand breaks and is linked to a rare immunodeficiency in humans, with few documented cases compared to the well-studied Scid mouse model.
- Seven patients with mutations in the PRKDC gene showed severe combined immunodeficiency symptoms, including granulomas and autoimmunity, highlighting a predominantly inflammatory clinical picture.
- Hematopoietic stem cell transplantation has proven effective for many, leading to meaningful recovery of T- and B-cell functions in the long-term follow-up of most patients.
Systemic lupus erythematosus is a rare and life-threatening autoimmune disease characterized by autoantibodies against double-stranded DNA, with an immunopathology that remains partially unclear. New insights into the disease have been provided by the discovery of key mutations leading to the development of monogenic SLE, occurring in the context of early-onset disease, syndromic lupus, or familial clustering. The increased frequency of discovering these mutations in recent years, thanks to the advent of genetic screening, has greatly enhanced our understanding of the immunopathogenesis of SLE.
View Article and Find Full Text PDFObjectives: - Janus Kinase inhibitors (JAKi) are a new class of drugs available for pediatric rheumatic diseases. This study aimed to describe the safety and effectiveness of JAKi in these diseases, with a focus on longitudinal interferon-stimulated genes (ISG) assessment.
Methods: - We present a single-center retrospective study of children with refractory pediatric rheumatic diseases including connective tissue diseases, monogenic type I interferonopathies or juvenile idiopathic arthritis, receiving JAKi.
Objectives: We aimed to compare clinical spectrum and outcome between adults and children with Takayasu's arteritis (TAK) in a European population.
Methods: We made a nationwide retrospective observational study between 1988 and 2019. All adult patients met the ACR diagnostic criteria for TAK and all children met the EULAR/PRINTO/PRES criteria for paediatric TAK.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by its large heterogeneity in terms of clinical presentation and severity. The pathophysiology of SLE involves an aberrant autoimmune response against various tissues, an excess of apoptotic bodies, and an overproduction of type-I interferon. The genetic contribution to the disease is supported by studies of monozygotic twins, familial clustering, and genome-wide association studies (GWAS) that have identified numerous risk loci.
View Article and Find Full Text PDFBackground: Our study aimed to provide real-world evidence on the treatment patterns, effectiveness and safety of canakinumab in France in Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD), and Tumor necrosis factor Receptor Associated Periodic Syndrome (TRAPS).
Methods: This study used the JIR cohort, a multicentre international registry created in 2013 to collect data on patients with juvenile inflammatory rheumatic diseases. French patients diagnosed with FMF, MKD or TRAPS and treated with canakinumab were included in this study.
Article Synopsis
- NLRP3-associated autoinflammatory disease is a collection of genetic disorders caused by mutations that lead to increased activity of the NLRP3 protein, which complicates diagnosis despite effective treatments available.
- The study explores 34 different NLRP3 mutations, illustrating their functional differences based on how they respond to various signals that activate them, and highlights their link to symptom severity and misdiagnosis.
- Findings reveal critical areas in the NLRP3 protein that affect its activity and response to treatments, offering new perspectives on the disorder's variability and potential directions for improving diagnosis and therapy.
Introduction: Multisystemic inflammatory syndrome in children (MIS-C) is a therapeutic emergency and can lead to myocardial dysfunction (17%-75%) and heart failure (52%-53%). Intravenous immunoglobulins (IVIG) and corticosteroids (CST) have been validated for the management of this condition. Recent reports suggest that an interleukin-1 (IL-1) receptor antagonist, namely anakinra, may be a valuable add-on to the 2019 novel coronavirus disease (COVID-19) treatment for refractory patients.
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