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399 results on '"Autoinflammatory Disorders"'

101. Immunization in multiple sclerosis and other childhood immune-mediated disorders of the central nervous system: A review of the literature

Author: Ismail Solmaz and Banu Anlar
Subjects: Central Nervous System, Pediatrics, medicine.medical_specialty, Multiple Sclerosis, Central nervous system, Immunological memory, 03 medical and health sciences, 0302 clinical medicine, Immune system, 030225 pediatrics, medicine, Humans, Child, Child care, Vaccines, business.industry, Multiple sclerosis, Vaccination, General Medicine, medicine.disease, medicine.anatomical_structure, Immunization, Pediatrics, Perinatology and Child Health, Neurology (clinical), business, 030217 neurology & neurosurgery, Autoinflammatory Disorders, Cohort study
Abstract: Childhood is a period where most vaccines are administered in order to build-up immunological memory, and immunization against vaccine-preventable diseases is an essential part of child care and health. The administration of vaccines to children with inflammatory diseases is a frequent point of concern for parents and physicians. Published information on the relation between vaccines and autoinflammatory diseases of the central nervous system (CNS) consists of case and cohort studies and reviews, in great majority on adult patients. Vaccines do not have any established causative or triggering effects on these diseases. Another issue is the immunization schedule of patients with autoinflammatory CNS diseases, specifically the interactions between the disorder, the clinical status, the treatment and the vaccine. In this review, we summarize the existing information between autoinflammatory disorders of the CNS and vaccines in childhood and underline the points to be considered under various treatment regimens.
Published: 2021

102. [Interstitial lung diseases in children of genetic origin].

Author: Nathan N
Subjects: Child, Humans, Phenotype, Mutation, Lung, Lung Diseases, Interstitial diagnosis, Lung Diseases, Interstitial genetics, Lung Diseases, Interstitial therapy, Pulmonary Alveolar Proteinosis diagnosis, Pulmonary Alveolar Proteinosis genetics, Pulmonary Alveolar Proteinosis therapy
Abstract: Interstitial lung diseases in children of genetic origin. Interstitial lung disease (ILD) in children (chILD) encompasses a heterogeneous group of rare respiratory disorders, most of which are chronic and severe. In more and more of these cases, a genetic cause has been identified. As of now, the main mutations have been localized in the genes encoding the surfactant proteins (SP)-C (SFTPC), SP-B (SFTPB), their transporter ATP-binding cassette, family 1, member 3 (ABCA3), transcription factor NK2 homeobox 1 (NKX2-1) and, more rarely, SP-A1 (SFTPA1) or SP-A2 (SFTPA2). Pediatric pulmonary alveolar proteinosis (PAP) is associated with mutations in CSF2RA, CSF2RB, and MARS; more recently, mutations in STING1 and COPA have been associated with specific auto-inflammatory disorders including ILD manifestations. The relationships between the molecular abnormalities and the phenotypic expressions generally remain poorly understood. In the coming years, it is expected that newly identified molecular defects will help to more accurately predict disease courses and to produce individualized targeted therapies., (Copyright © 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.)
Published: 2023
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103. Dysregulated production of interleukin-1β upon activation of the NLRP3 inflammasome in patients with familial Mediterranean fever.

Author: Repa, Argyro, Bertsias, George K., Petraki, Eleni, Choulaki, Christianna, Vassou, Despoina, Kambas, Konstantinos, Boumpas, Dimitrios T., Goulielmos, George, and Sidiropoulos, Prodromos
Subjects: *FAMILIAL Mediterranean fever, *ALVARADO score, *EXANTHEMA, *BODY temperature, *MEDICAL care
Abstract: Familial Mediterranean fever (FMF) is caused by mutations in pyrin, a protein expressed in innate immune cells that interacts with caspase-1 and other inflammasome components to regulate interleukin (IL)-1β maturation. Since NLRP3 inflammasome represents major source of IL-1β, we studied its protein expression and function in FMF. We isolated peripheral white blood cells (WBCs) from 20 symptoms-free FMF patients and 21 healthy individuals. Intracellular protein expression of NLRP3, caspase-1, IL-1β at baseline and after LPS/ATP sequential treatment for NLRP3 activation was assessed by immunoblotting. Secreted IL-1β was quantified by ELISA. THP-1 cells were transfected with wild-type or mutant pyrin and IL-1β secretion was measured. FMF WBCs exhibited lower NLRP3 and active caspase-1 protein expression compared to healthy individuals, and LPS/ATP treatment resulted in significantly lower intracellular IL-1β levels in FMF patients. Likewise, LPS/ATP induced caspase-1-dependent IL-1β release at significantly lower amounts in the FMF group (1182 ± 192 versus 2134 ± 245 pg/mL in controls, p = 0.004). Consistently, THP-1 cells transfected with FMF-associated M694V mutant pyrin displayed lower LPS/ATP-induced IL-1β compared with wild-type pyrin-transfected cells. FMF WBCs demonstrate reduced NLRP3-mediated IL-1β production. Additional studies are needed to define whether this finding represents a compensatory mechanism to control inflammation or is directly linked to disease pathogenesis. [ABSTRACT FROM AUTHOR]
Published: 2015
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104. Anakinra treatment in patients with gout and type 2 diabetes.

Author: Vitale, Antonio, Cantarini, Luca, Rigante, Donato, Bardelli, Marco, and Galeazzi, Mauro
Subjects: *GOUT, *PEOPLE with diabetes, *CAUCASIAN race, *INTERLEUKIN-1 receptor antagonist protein, *ANTI-inflammatory agents, *PREDNISONE, *PATIENTS, *DISEASES
Abstract: We report three Caucasian patients affected by gout and type 2 diabetes, who were treated with the recombinant nonglycosylated human interleukin-1 receptor antagonist anakinra (100 mg/day subcutaneously) after an unsatisfactory or incomplete response to urate-lowering therapy, colchicine, nonsteroidal anti-inflammatory drugs, and prednisone. The remarkable clinical improvement in joint symptoms within 24 h and in glycemic control during a 6-month period gives anakinra a potential therapeutic role in the management of gout and type 2 diabetes. When anakinra was discontinued, a gout attack occurred within 3-25 days in all three patients. The contribution of anakinra in the treatment of such syndromes is encouraging, but requires further studies to establish its long-term efficacy. [ABSTRACT FROM AUTHOR]
Published: 2015
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105. Overlap of Familial Mediterranean Fever and Hyper-IgD Syndrome in an Arabic Kindred.

Author: Moussa, Taha, Aladbe, Buthaina, Taha, Rowaida, Remmers, Elaine, El-Shanti, Hatem, and Fathalla, Basil
Subjects: *FAMILIAL Mediterranean fever, *IMMUNOGLOBULIN D, *GENETIC mutation, *HOMOZYGOSITY, *ABDOMINAL pain, *GENETIC testing
Abstract: Hyperimmunoglobulinemia D Syndrome (HIDS) has rarely been reported in Arabs. Moreover, the simultaneous presence of mutations in MEFV and MVK segregating in the same family is exceptional. We report an Arabic girl presenting since the age of 8-years with two patterns of recurrent episodes of fever, and associated with a spectrum of clinical features suggestive of overlap between familial Mediterranean fever (FMF) and HIDS. Her 19-year old brother presented since the age of 1 year with prolonged episodes of fever and was diagnosed with HIDS at the age of 7 years based on clinical features and homozygosity for p.V377I mutation in MVK. Shorter episodes of fever and abdominal pain more consistent with FMF ensued since the age of 17 years. Genetic testing done for both patients and all other family members revealed simultaneous presence of mutations in MEFV and MVK but with a variable clinical spectrum ranging from asymptomatic to severe manifestations. Both of our patients are homozygous for p.V377I MVK mutation; the girl is a compound heterozygote for p.E148Q/p.P369S/p.R408G and p.E167D/p.F479L MEFV mutations whereas the brother is a compound heterozygote for p.E148Q/p.P369S/p.R408G and p.M680I MEFV mutations. The clinical implications of having more than one mutation in different genes of monogenic autoinflammatory diseases in the same individual are not clear but may explain atypical clinical manifestations such as the overlap features of both FMF and HIDS in this family. [ABSTRACT FROM AUTHOR]
Published: 2015
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106. Overview of the rarest causes of fever in newborns: handy hints for the neonatologist

Author: De Rose, D. U., Coppola, Maria, Gallini, Francesca, Maggio, Luca, Vento, Giovanni, Rigante, Donato, Coppola M., Gallini F. (ORCID:0000-0002-9510-8481), Maggio L. (ORCID:0000-0001-6358-7775), Vento G. (ORCID:0000-0002-8132-5127), Rigante D. (ORCID:0000-0001-7032-7779), De Rose, D. U., Coppola, Maria, Gallini, Francesca, Maggio, Luca, Vento, Giovanni, Rigante, Donato, Coppola M., Gallini F. (ORCID:0000-0002-9510-8481), Maggio L. (ORCID:0000-0001-6358-7775), Vento G. (ORCID:0000-0002-8132-5127), and Rigante D. (ORCID:0000-0001-7032-7779)
Abstract: Neonatal causes of fever are a major source of concern for clinicians. If fever is combined with organ-specific sterile inflammatory manifestations the suspicion of autoinflammatory disorders should be considered, and the list of such conditions starting in the neonatal period includes chronic infantile neurological cutaneous articular syndrome, mevalonate kinase deficiency, deficiency of the interleukin-1 receptor antagonist, otulipenia, STING-associated vasculopathy with onset in infancy and Blau syndrome. Other causes of noninfectious fever that can rarely occur in newborns are Kawasaki disease, Behçet’s disease, and hemophagocytic lymphohistiocytosis. Diagnosis of these exceptionally rare disorders is challenging for neonatologists. An early recognition of these complex diseases might lead to use more specific or rational drugs preventing permanent consequences. This review focuses on the rarest causes of fever occurring in the neonatal age with the aim of portraying many protean clinical pictures associated with fever and reviewing the potential available treatments.
Published: 2020

107. Systemic autoinflammatory disease in adults

Author: Daniel Engelbert Blockmans, Isabelle Meyts, Frederik Staels, Rik Schrijvers, Albrecht Betrains, Stephanie Humblet-Baron, Ellen De Langhe, Carine Wouters, and Steven Vanderschueren
Subjects: 0301 basic medicine, Adult, medicine.medical_specialty, Abdominal pain, Autoinflammatory disease, Fever, Immunology, Inflammation, Disease, SAID, 03 medical and health sciences, 0302 clinical medicine, Rare Diseases, medicine, Immunology and Allergy, Humans, In patient, Child, Genetic testing, 030203 arthritis & rheumatology, Innate immunity, medicine.diagnostic_test, business.industry, Innate immune system, Hereditary Autoinflammatory Diseases, Dermatology, Pathophysiology, 030104 developmental biology, Immune System Diseases, Autoinflammation, medicine.symptom, business, Autoinflammatory Disorders
Abstract: 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 established in childhood, but a growing number of adult patients are being recognized with systemic autoinflammatory disorders, including adult-onset disease. In this review, we provide a concise update on the pathophysiology, clinical presentation, and diagnostic approach of systemic autoinflammatory disorders with an emphasis on the adult patient population. Despite the recent advances in genetic testing, the diagnosis of autoinflammatory disease in adult patients is often based on a thorough knowledge of the clinical phenotype. Becoming acquainted with the clinical features of these rare disorders may assist in developing a high index of suspicion for autoinflammatory disease in patients presenting with unexplained episodes of fever or inflammation. ispartof: AUTOIMMUNITY REVIEWS vol:20 issue:4 ispartof: location:Netherlands status: published
Published: 2020

108. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity

Author: Picard, Capucine, Bobby Gaspar, H., Al-Herz, Waleed, Bousfiha, Aziz, Casanova, Jean-Laurent, Chatila, Talal, Crow, Yanick J., Cunningham-Rundles, Charlotte, Etzioni, Amos, Franco, Jose Luis, Holland, Steven M., Klein, Christoph, Morio, Tomohiro, Ochs, Hans D., Oksenhendler, Eric, Puck, Jennifer, Tang, Mimi L. K., Tangye, Stuart G., Torgerson, Troy R., and Sullivan, Kathleen E.
Published: 2017
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109. Recurrent Fever in Children

Author: Sofia Torreggiani, Giovanni Filocamo, and Susanna Esposito
Subjects: autoinflammatory disorders, pediatric infectious diseases, periodic fever, recurrent fever, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Children presenting with recurrent fever may represent a diagnostic challenge. After excluding the most common etiologies, which include the consecutive occurrence of independent uncomplicated infections, a wide range of possible causes are considered. This article summarizes infectious and noninfectious causes of recurrent fever in pediatric patients. We highlight that, when investigating recurrent fever, it is important to consider age at onset, family history, duration of febrile episodes, length of interval between episodes, associated symptoms and response to treatment. Additionally, information regarding travel history and exposure to animals is helpful, especially with regard to infections. With the exclusion of repeated independent uncomplicated infections, many infective causes of recurrent fever are relatively rare in Western countries; therefore, clinicians should be attuned to suggestive case history data. It is important to rule out the possibility of an infectious process or a malignancy, in particular, if steroid therapy is being considered. After excluding an infectious or neoplastic etiology, immune-mediated and autoinflammatory diseases should be taken into consideration. Together with case history data, a careful physical exam during and between febrile episodes may give useful clues and guide laboratory investigations. However, despite a thorough evaluation, a recurrent fever may remain unexplained. A watchful follow-up is thus mandatory because new signs and symptoms may appear over time.
Published: 2016
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110. Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) Syndrome in Iranian Children First Report of Iranian Periodic Fever and Autoinflammatory Registry (IPFAIR).

Author: Mehregan, Fatemeh Fereshteh, Ziaee, Vahid, Ahmadinejad, Zahra, Tahghighi, Fatemeh, Sabouni, Farah, and Moradinejad, Mohamad-Hassan
Subjects: *AUTOIMMUNE diseases, *CHI-squared test, *REPORTING of diseases, *FEVER, *GENETIC disorders, *INFLAMMATION, *LONGITUDINAL method, *LYMPHADENITIS, *NECK, *PHARYNGITIS, *REPORT writing, *RESEARCH funding, *SYNDROMES, *T-test (Statistics), *DISEASE relapse, *CANKER sores, *DATA analysis software, *DESCRIPTIVE statistics
Abstract: Objective: The periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is a nonhereditary idiopathic febrile syndrome belonging to the group of autoinflammatory diseases. No longtime sequel was reported in this disease. Early diagnosis can lead physicians to treatment of this disorder with a short course steroid application and provide satisfaction of the patient’s family. Methods: This study is a prospective review of patients diagnosed with PFAPA syndrome who were registered in Iranian Periodic Fever and Autoinflammatory Registry (IPFAIR) through periodic fever clinic in the Children's Medical Center, Pediatric Center of Excellence in Tehran, Iran from January 2013 to March 2014. Findings: One hundred thirty patients were registered in our databases. Twenty-one (16.1%) patients including 15 males and 6 females had PFAPA. Normal growth was seen in all patients. The median age at onset was 18 months. The mean duration of fever was 4 days and the mean duration of intervals between fever episodes 21 days. Along with fever, all patients had characteristic symptoms. All patients were asymptomatic between fever episodes. Steroid was used in all patients and causing immediate reduction by 84.61%. Two patients received both steroid and colchicine because of their clinical feature and positive laboratory tests for PFAPA and familial Mediterranean fever. No patient received biological therapy or a tonsillectomy. Conclusion: The long diagnostic delay of PFAPA gives cause to concern indicating a need for greater awareness of the disease so that the diagnosis may be made timely. [ABSTRACT FROM AUTHOR]
Published: 2014

111. The expanding spectrum of low-penetrance TNFRSF1A gene variants in adults presenting with recurrent inflammatory attacks: Clinical manifestations and long-term follow-up.

Author: Cantarini, Luca, Rigante, Donato, Merlini, Giampaolo, Vitale, Antonio, Caso, Francesco, Lucherini, Orso Maria, Sfriso, Paolo, Frediani, Bruno, Punzi, Leonardo, Galeazzi, Mauro, Cimaz, Rolando, and Obici, Laura
Abstract: Abstract: Objective: To analyze the clinical manifestations and response to treatment in a cohort of adult patients presenting with recurrent inflammatory attacks and carrying low-penetrance TNFRSF1A variants, as well as to provide data on their long-term follow-up. Methods: We performed a retrospective chart review of 36 patients carrying low-penetrance TNFRSF1A variants. Moreover, 60 genetically negative patients treated for recurrent inflammatory attacks and 13 patients with structural TNFRSF1A mutations were also analyzed. Detailed demographic and clinical data were collected at the time of molecular screening and at each follow-up visit. Treatments and markers of inflammation were also assessed. Results: Individuals with low-penetrance TNFRSF1A variants have a lower family history for inflammatory attacks and present with a later disease onset compared with patients with structural mutations, but do not differ, in this respect, with genetically negative individuals. Moreover, low-penetrance variants are less frequently associated with a chronic disease course, with clinical manifestations such as abdominal pain and myalgia, and with amyloidosis. A distinctive clinical feature is a higher rate of pericarditis. Interestingly, mutation-negative patients were found to present with a significant history of recurrent pharyngitis during childhood. Patients with low-penetrance variants are mostly managed with short courses of steroids or non-steroidal anti-inflammatory drugs on attacks. Although the need for a biological treatment is significantly lower compared with patients with structural mutations, still approximately 20% of individuals with recurrent inflammatory attacks carrying low-penetrance variants ultimately require these therapies. Conclusions: Our study confirms that low-penetrance TNFRSF1A variants can be associated with an autoinflammatory phenotype. Although a chronic disease course is rarely observed, some patients ultimately benefit from a biological treatment. [Copyright &y& Elsevier]
Published: 2014
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112. Association between pemphigus and psoriasis: a systematic review and meta-analysis

Author: Kevin Phan, Vignesh Ramachandran, and Saxon D Smith
Subjects: medicine.medical_specialty, integumentary system, business.industry, MEDLINE, Dermatology, General Medicine, medicine.disease, Pemphigus, immune system diseases, Meta-analysis, Psoriasis, medicine, Humans, In patient, skin and connective tissue diseases, Association (psychology), business, Autoinflammatory Disorders
Abstract: Pemphigus has been associated with other autoimmune and autoinflammatory disorders. Specifically, some case reports in the literature document coexistence of pemphigus with psoriasis, but this association is lacking larger scale investigation. With this in mind, we conducted a systematic review and meta-analysis to evaluate the association between pemphigus and psoriasis. In doing so, we found an association between the two conditions. Pemphigus was more common in patients with psoriasis than in controls (OR 2.64, 95% CI 1.24-5.59, P=0.01), with heterogeneity (I2=94%). We go on to propose pathophysiologic mechanisms and its relevance for diagnostic and management considerations.
Published: 2020

113. Misleading symptoms of hereditary angioedema type II mimicking familial mediterranean fever

Author: Marko Barešić, Karanović, B., Coen Herak, D., Kozmar, A., and Anić, B.
Subjects: Diagnosis, Differential, Hereditary Angioedema Types I and II, Humans, Familial mediterranean fever, Autoinflammatory disorders, Oedema, Female, Middle Aged, Familial Mediterranean Fever
Abstract: Hereditary angioedema (HAE) is a rare, debilitating and potentially life-threatening disease characterized by recurrent attacks of oedema. With the development of new therapies and better availability of diagnostic tools, important advances have been made. However, the disease still remains frequently misdiagnosed and inadequately treated. Familial Mediterranean fever (FMF) is an autoinflammatory syndrome comprised of serositis, fever, arthritis and skin involvement. Both diseases can cause severe abdominal pain resembling that of acute abdomen. We report a case of three family members that presented with various symptoms that could fit in a clinical picture of both diseases, only to confirm a diagnosis of HAE type II after a diagnostic delay of many years.
Published: 2020

114. Association of Clinical Phenotypes in Haploinsufficiency A20 (HA20) With Disrupted Domains of A20

Author: Fang Xiao, Ursula Seidler, Zhenghao Ye, Tingting Qin, Liping Chen, Dean Tian, and Yu Chen
Subjects: 0301 basic medicine, Male, DNA Mutational Analysis, Disease, Haploinsufficiency, medicine.disease_cause, TNFAIP3, Gastroenterology, Ovarian tumor, haploinsufficiency A20, 0302 clinical medicine, Immunology and Allergy, Age of Onset, Child, Oral Ulcer, Original Research, Mutation, clinical manifestation, Phenotype, Child, Preschool, Female, lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Heterozygote, Peptic Ulcer, Adolescent, Fever, OTU domain, Immunology, Monogenic disease, Diagnosis, Differential, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Humans, Sex organ, Genetic Predisposition to Disease, Tumor Necrosis Factor alpha-Induced Protein 3, business.industry, Hereditary Autoinflammatory Diseases, Infant, 030104 developmental biology, monogenic disease, autoinflammatory disorders, ZnF domain, business, lcsh:RC581-607, 030215 immunology
Abstract: Background: Haploinsufficiency A20 (HA20) is a newly described monogenic disease characterized by a wide spectrum of manifestations and caused by heterozygous mutations in TNFAIP3 which encodes A20 protein. TNFAIP3 mutation leads to disruption of the A20 ovarian tumor (OTU) domain and/or the zinc finger (ZnF) domain. This study aims at exploring the association between the various manifestations of HA20 and different domains disruption of A20. Methods: We reviewed the HA20 cases in previous literature and summarized the clinical features, TNFAIP3 mutation loci and the disrupted domains caused by different sites and patterns of mutations. Patients were classified into three groups according to the A20 domains disruption. Results: A total of 89 patients from 39 families with a genetic diagnosis of HA20 were included. Overall, the age at onset of HA20 was early (median:5.92, IQR:1-10). Patients in the ZnF group showed the earliest onset (median:2.5, IQR:0.6-5), followed by patients in the OTU+ZnF group (median:6, IQR:1-10) and patients in the OTU group (median:10, IQR:8-14). The main manifestations of HA20 patients were recurrent oral ulcers (70%), recurrent fever (42%), gastrointestinal ulcers (40%), skin lesion (38%), genital ulcers (36%), and musculoskeletal disorders (34%). The percentage of patients with musculoskeletal disorders was significantly different among the three groups (p = 0.005). Patients in the OTU+ZnF group and ZnF group were more likely to develop musculoskeletal disorders than patients in the OTU group (p = 0.002 and p = 0.035, respectively). Besides, forty-three percent of HA20 patients were initially diagnosed as Behcet's disease (BD). Compared to the ZnF group, the OTU+ZnF group and OTU group had a higher percentage of patients initially diagnosed as BD (p = 0.006 and p < 0.001, respectively). Conclusion: HA20 is characterized by early-onset and the most common symptoms of HA20 are recurrent oral ulcers, fever and gastrointestinal ulcers. The onset of HA20 in patients with the ZnF domain disruption is earlier than patients with the OTU domain disruption. Compared to the OTU domain, the ZnF domain may be more closely related to musculoskeletal disorders.
Published: 2020

115. The neutrophil inflammasome

Author: Sylwia D. Tyrkalska, Sergio Candel, and Victoriano Mulero
Subjects: 0301 basic medicine, Inflammasomes, Neutrophils, Immunology, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Immune system, NLRC4, GTP-Binding Proteins, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Macrophage, Animals, Humans, Zebrafish, Innate immune system, biology, Macrophages, Inflammasome, biology.organism_classification, Disease Models, Animal, 030104 developmental biology, Autoinflammatory Disorders, 030215 immunology, Developmental Biology, medicine.drug
Abstract: Since inflammasomes were discovered in the early 21st century, knowledge about their biology has multiplied exponentially. These cytosolic multiprotein complexes alert the immune system about the presence of infection or tissue damage, and regulate the subsequent inflammatory responses. As inflammasome dysregulation is increasingly associated with numerous autoinflammatory disorders, there is an urgent need for further research into the inflammasome's involvement in the pathogenesis of such diseases in order to identify novel therapeutic targets and treatments. The zebrafish has become a widely used animal model to study human diseases in recent years, and has already provided relevant findings in the field of inflammasome biology including the identification of new components and pathways. We provide a detailed analysis of current knowledge on neutrophil inflammasome biology and compare its features with those of the better known macrophage inflammasome, focusing on its contribution to innate immunity and its relevance for human health. Importantly, a large body of evidence points to a link between neutrophil inflammasome dysfunction and many neutrophil-mediated human diseases, but the real contribution of the neutrophil inflammasome to the pathogenesis of these disorders is largely unknown. Although neutrophils have remained in the shadow of macrophages and monocytes in the field of inflammasome research since the discovery of these multiprotein platforms, recent studies strongly suggest that the importance of the neutrophil inflammasome has been underestimated.
Published: 2020

116. Current Insights in Genetics of Sarcoidosis: Functional and Clinical Impacts

Author: Alain Calender, Dominique Valeyre, Thomas Weichhart, and Yves Pacheco
Subjects: autophagy, Complex disease, lcsh:Medicine, Genome-wide association study, Computational biology, Disease, Review, DNA sequencing, 03 medical and health sciences, 0302 clinical medicine, Medicine, genetics, sarcoidosis, innate immunity, Exome sequencing, 030304 developmental biology, 0303 health sciences, business.industry, T cell activation, Multifactorial disease, lcsh:R, General Medicine, medicine.disease, 030220 oncology & carcinogenesis, mTOR, Sarcoidosis, business, Autoinflammatory Disorders
Abstract: Sarcoidosis is a complex disease that belongs to the vast group of autoinflammatory disorders, but the etiological mechanisms of which are not known. At the crosstalk of environmental, infectious, and genetic factors, sarcoidosis is a multifactorial disease that requires a multidisciplinary approach for which genetic research, in particular, next generation sequencing (NGS) tools, has made it possible to identify new pathways and propose mechanistic hypotheses. Codified treatments for the disease cannot always respond to the most progressive forms and the identification of new genetic and metabolic tracks is a challenge for the future management of the most severe patients. Here, we review the current knowledge regarding the genes identified by both genome wide association studies (GWAS) and whole exome sequencing (WES), as well the connection of these pathways with the current research on sarcoidosis immune-related disorders.
Published: 2020

117. How to handle the main drugs to treat autoinflammatory disorders and how we treat common autoinflammatory diseases

Author: Perrine Dusser and Isabelle Koné-Paut
Subjects: medicine.medical_specialty, Mevalonate kinase deficiency, business.industry, Familial Mediterranean fever, Dermatology, medicine.disease, TNF Receptor-Associated Factor 1, Cryopyrin-Associated Periodic Syndromes, Familial Mediterranean Fever, Clinical Practice, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Periodic syndrome, Tnf receptor 1, medicine, Humans, Mevalonate Kinase Deficiency, Intensive care medicine, business, Deficiency Diseases, Autoinflammatory Disorders
Abstract: This article provides an overview of the main drugs to treat autoinflammatory disorders focusing on the four emblematic diseases within this group which represent, to date, the vast majority of patients with monogenic SAID; i.e. familial Mediterranean fever, mevalonate kinase deficiency, TNF receptor 1 deficiency and cryopyrin-associated periodic syndrome. We will therefore resume the evolutionary risks of the four main IL-1 dependent SAID, there treatments and monitoring tools. After having exposed the general principles, we will detail specific guidelines for the management in everyday clinical practice of patients according to the four main pathologies based on both our expertise and international recommendations. We aim herein to guide practitioners in charge of patients with common SAID towards optimal follow-up with appropriate monitoring of anti-inflammatory drugs.
Published: 2020

118. Clinical characteristics of 17 patients with COVID-19 and systemic autoimmune diseases: a retrospective study

Author: Xin Ba, Hui Wang, Zhe Chen, Hui Dong, Liang Han, Mingmin Zhang, Yu Wang, Weiji Lin, Shenghao Tu, Wenya Huang, Kai Qin, Pan Shen, Ying Huang, and Yao Huang
Subjects: Male, Comorbidity, Comorbidities, law.invention, 0302 clinical medicine, law, Epidemiology, Medicine, Immunology and Allergy, 030212 general & internal medicine, Registries, Young adult, Public health, education.field_of_study, glucocorticoids, Middle Aged, Research Highlight, Intensive care unit, Hospitalization, Intensive Care Units, Autoinflammatory Disorders, Female, epidemiology, Coronavirus Infections, Adult, China, medicine.medical_specialty, hydroxychloroquine, Adolescent, Population, Pneumonia, Viral, Immunology, General Biochemistry, Genetics and Molecular Biology, Young Adult, 03 medical and health sciences, Betacoronavirus, Acquired immunodeficiency syndrome (AIDS), Rheumatology, Internal medicine, Rheumatic Diseases, Humans, autoimmune diseases, education, Pandemics, Aged, Retrospective Studies, 030203 arthritis & rheumatology, Inpatients, business.industry, SARS-CoV-2, COVID-19, Retrospective cohort study, medicine.disease, Clinical trial, Viral infection, business
Abstract: ObjectivesIncreasing data about COVID-19 have been acquired from the general population. We aim to further evaluate the clinical characteristics of COVID-19 in patients with systemic autoimmune diseases (AIDs).MethodsWe included all confirmed inpatients with COVID-19 and systemic AIDs in Wuhan Tongji Hospital from 29 January to 8 March 2020. We retrospectively collected and analysed information on epidemiology of 1255 inpatients and additional clinical characteristics of patients with systemic AIDs. Outcomes were followed up until 16 April 2020.ResultsOf the 1255 patients with COVID-19, the median age was 64.0 years and 53.1% were male. More than half (63.0%) had chronic comorbidities. The proportions of elderly, male and patients with comorbidities were significantly higher in intensive care unit (ICU) than in the general ward (pConclusionsOlder males with chronic comorbidities are more vulnerable to severe COVID-19. The lower proportion of COVID-19 in patients with systemic AIDs needs more high-quality human clinical trials and in-depth mechanism researches. Of note, the withdrawal of anti-AIDs treatments during hospitalisation can lead to flares of diseases.
Published: 2020
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119. Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

Author: Victor Judith, Devaux Mathilde, Corre Clémence, Morin Franck, Ebstein Esther, Desmurs Marie, Juillard Laurent, Descamps Elise, Galland Joris, Gahier Penhoat Mélanie, Hellier Jean-Pierre, Mariette Xavier, Poix Elsa, Hudry Christophe, Constant Elodie, Trijau Sophie, Moranne Olivier, Diot Elisabeth, Hie Miguel, Guilpain Philippe, Boussoualim Karima, Mathian Alexis, Pouchot Jacques, Rohmer Julien, Senet Patricia, Michaud Martin, Tieulie Nathalie, Liote Frédéric, Ducornet Angélique, Couret Marie, Revuz Sabine, Morel Hugo, Moly Marie, Direz Guillaume, Milesi-Lecat Anne-Marie, Meinzer Ulrich, Bader-Meunier Brigitte, Steib Sarah, Gauthier-Prieur Maud, Bertolini Ewa, Gombert Bruno, Dumel Anne-Elisabeth, Henriot Basile, Froissart Antoine, Smets Perrine, Robin Sophie, Rousselin Clémentine, Moulinier Laurence, Mazet-Guillaume Betty, Brondino Regine, Malochet-Guinamand Sandrine, Balandraud Nathalie, Gibert Christelle, Godeau Bertrand, Aeschlimann Florence, Bonnet Christine, Plassard Samira, Lebrun Agnès, Mehsen-Cetre Nadia, Arlet Jean-Benoît, Gagneux-Lemoussu Laurence, Kemiche Farid, Michon Mathilde, Szafors Paulina, Werle Claude, Guillaud Constance, La Batide Alanore Sylvain, Borie Raphaël, Chazerain Pascal, Puyraimond-Zemmour Déborah, Barrelet Audre, Bach-Bunner Maxime, Flaisler Françoise, Euvrard Romain, Evon Philippe, Feurer Elodie, Gerard Nathalie, Gervais Elisabeth, Sordet Christelle, Bally Stéphane, Mazouyez Arnaud Angers, Guillot Xavier, Comarmond Chloé, Leloire Olivier, Fauconier Marion, Bouhour Françoise, Woessner Juliette, Jaccard Clara, Langlois Vincent, Sicaud Aurélie, Rolland Michel, Kabala Anna, Atlan Lucie, Amador-Borreiro Blanca, Jan Catherine, Leturcq Tifenn, Gonnet-Gracia Camille, Lanot Sylvain, Hachulla Eric, Bonidan Olivier, Domont Fanny, Dumaine Cécile, Bouiller Kévin, Senbel Eric, Comparon Céline, Huguenel Serge, Despaux Jacques, Roth Olivier, Berthoux Emilie, Dehimat Sarahe, Costedoat-Chalumeau Nathalie, Bayer Guillaume, Melki Isabelle, Toussirot Eric, Buchlin Pierre, Baumier Vincent, Charcot Agnès, Durand Géraldine, Garraud Thomas, Richez Christophe, Gillard Jérôme, Chaigne Benjamin, Rousiere Mickaël, Le Guen Guegan Sophie, Chertok Pascale, Lucas Virginie, Sadji Fatiha, Garnier Nicole, Sailler Laurent, Garrot Jean-François, Taffignon-Clave Séverine, Charles Pierre, Bernoux-Manat Brigitte, Salliot Carine, Fechtenbaum Jacques, Quenet Marion, Le Guenno Guillaume, Lanteri Aurélia, Hermet Marion, Delahousse Michel, Basch André, Grateau Gilles, Chevalier Xavier, Nocturne Gaétane, Schmidt Jean, Pacaud-Vitoux Isabelle, Roumier Mathilde, Rozenberg Sylvie, Veillard Eric, Roux Nicolas, Marhadour Thierry, Colette-Cedoz Marie-Eve, Cohen Gregory, Foltz Violaine, Fouque-Aubert Anne, Havard Marie-Noelle, Molto Anna, Chevreau Maxime, Strotz Victor, Allanore Yannick, Grardel Bruno, Francois-Pradier Hélène, Devauchelle-Pensec Valérie, Hennequin Pascal, Warzocha Ursula, Collercandy Nived, Bayle Sophie, Audren Victor, Virone Alexandre, Bennet Pascal, Grados Franck, Charpin Caroline, Fuzibet Piera, Albert Jean-David, Larbre Jean-Paul, Coutarel Cécile, Nicolas-Vullierme Sabine, Gastaldi Romain, Guyot Marie-Hélène, Georgescu Dana, Clavel Gaëlle, Tison Alice, Viallard Jean-François, Maria Alexandre, Glanowski Camille, Leroux Christophe, Vidon Mathias, Banal Frédéric, Fulpin Jean, Chotard Emilie, Gaud-Listrat Véronique, Jean Sylvie, Seguier Julie, Jacquemier Jean-Michel, Chatelus Emmanuel, Djeddi Djamal-Dine, Contamine-Sur-Arve Mazyad Hassan, Georgin-Lavialle Sophie, Belot Alexandre, Seve Pascal, Willems Alexandra, Moulis Guillaume, Latourte Augustin, Roux Marielle, Bolla Gilles, Renard Myriam, Xerri-Campano Bernadette, Bisson-Vaivre Aurélia, Fichet Amandine, Dufauret-Lombard Carine, Nielly Hubert, Ledoult Emmanuel, Alcais Didier, Giraudet-Le Quintrec Jeanine-Sophie, Wendling Daniel, Govindaraju-Audouard Sophie, Claudepierre Pascal, Fritz Pierre, Fougerousse Anne-Claire, Marotte Hubert, Fabre Sylvie, Banneville Béatrice, Quartier-Dit-Maire Pierre, Juge Pierre-Antoine, Moura Bertrand, Maillet Thibault, Messer Laurent, Thomachot Benoît, Giraud-Morelet Aude, Sparsa Lætitia, Kabchou Abdelkrim, Grasland Anne, Maurier François, Belin Véronique, Grenoble Gimonnet Pauline, Balblanc Jean-Charles, Andre Emma, Veillard Ericveillard Marie-Eliseeric, Chu Miow Lin, Pugnet Grégory, Wisniewski Michel, Carbasse Aurélia, Rene Jessica, Economu-Dubosc Andra, Bouldoires Bastien, Glace Baptiste, Benhamou Mathilde, Legoupil Nathalie, Morel Jacques, Castel Brice, Lafforgue Pierre, Carteni Maurizio, Lohse Anne, Detree Frédérick, Celant Annalisa, Trefond Ludovic, Maillard Hélène, Remy Philippe, Barnetche Thomas, Servettaz Amélie, Vigne Camille, Ferreira-Maldent Nicole, Mangon Quentin, Keraen Jérémy, Fautrel Bruno, Frantzen Léa, Legrand Erick, Sellam Jérémie, Tenenbaum Nora, Sene Thomas, Duc Catherine, Bouvard Eric, Dieudonne Yannick, Ollagnon Henri-Olivier, Deslandre Chantal, Gury Aline, Desplats Marie, Karman Françoise, Drouet Béatrice, Vidon Claire, Kone-Paut Isabelle, Groza Monica, Jamard Bénédicte, Parrot Antoine, Vial Guillaume, Ebbo Mikaël, Ait-Abdallah Nassim, Veillon Laurent, Roriz Mélanie, Chaillous Benoît, Rouidi Sid-Ahmed, Sobanski Vincent, Poulet Antoine, Clavel-Osorio Cyril, Nguyen Minh, Felten Renaud, Goulenok Tiphaine, Audoin-Pajot Christine, Foret Jennifer, Arniaud Denis, Benammar Mohammed, Boudou Laurence, Pascaud-Mansour Yasmina, Pavy Stephan, Sornay-Rendu Elisabeth, Pascart Tristan, Madelon Aurélie, Koreichi Abdeldajallil, Flipo René-Marc, El Mahou Soumaya, Benmansour Ahmed, Arty-Hue Herliette, Pers Yves-Marie, Hittinger-Roux Ambre, Sacco Isabelle, Fernandes Fanny, Gandjbakhch Frédérique, Maury Frédéric, Hacquard-Bouder Cécile, Foutrier-Morello Catherine, Rossi Linda, Belkhir Rakiba, Riviere Etienne, Drumez Elodie, Avouac Jérôme, Benainous Ruben, Champy Romuald, Florens Nans, Pichon Maud, Gibert Eric, Benhamou Ygal, Portier Agnès, Riviere Sébastien, Pham Thao, Blaison Gilles, Colombey Antoine, Marchou-Lopez Sylvie, Roux Fabienne, Leroy Rémi, Lejeune Charlotte, Bacquet-Deschryver Hélène, Romier Mélanie, Simoens Justine, Caumont Hervé, Arnaud Laurent, Paulin Lætitia, Duret Pierre-Marie, Dieude Philippe, Coury-Lucas Fabienne, Pha Micheline, Herasse Muriel, Mahevas Matthieu, Roitg Isabelle, Karkowski Ludovic, Dhote Robin, Chaudier Bernard, Gourmelen Olivier, Trouillier Sébastien, Henry Julien, Daver-Malaterre Laurence, Cathebras Pascal, Goupille Philippe, Seror Raphaële, Thomas Thierry, Pertuiset Edouard, Amoura Zahir, Richard-Colmant Gaëlle, Souchaud-Debouverie Odile, Lahalle Sophie, Jouvray Mathieu, Hentgen Véronique, Courvoisier Natacha, Charlot-Lambrecht Isabelle, Damade Richard, Argenteuil Pizana Gabrielle, Fontanges Elisabeth, Morel Gautier, Roux Christian, Perard Laurent, Gaches Francis, Cacoub Patrice, Mekinian Arsène, Cohen Fleur, Margarit Nathalie, Salmon Jean-Hugues, Guillaume Séverine, Gilson Mélanie, Coutier Fabrice, Rouzaud Diane, Duhamel Alain, Combe Bernard, Jullien Denis, Gill Ghislaine, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Saint-Joseph [Marseille], UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPCité Médecine Paris Centre), Université Paris Cité (UPCité), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Necker - Enfants Malades [AP-HP], CH Belfort-Montbéliard, Service de néphrologie - dialyse [Centre hospitalier Métropole Savoie - Chambéry], Centre Hospitalier Métropole Savoie [Chambéry], Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Avicenne [AP-HP], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de rééducation et de réadaptation de l'appareil locomoteur et des pathologies du rachis [CHU Cochin], CHU Rouen, Normandie Université (NU), Centre hospitalier Saint Joseph - Saint Luc [Lyon], Médecine interne [Hôpitaux civils de Colmar], Hôpitaux Civils de Colmar, Institut national de recherches archéologiques préventives (Inrap), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Electroneuromyographie et Service de Neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital Cochin [AP-HP], PSA Peugeot Citroën (PSA), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Hôpital d'Instruction des Armées Laveran, Service de rhumatologie [Groupe Hospitalier Diaconesses Croix Saint Simon], Groupe Hospitalier Diaconesses Croix Saint-Simon, Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation Ophtalmologique Adolphe de Rotschild, Service de Médecine Intensive et Réanimation [Tours], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), AGROCAMPUS OUEST, Hôpital Foch [Suresnes], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Médecine Interne [CHI Poissy-Saint-Germain], Centre Hospitalier Intercommunal de Poissy-Saint Germain-en-Laye (CHI Poissy-Saint Germain-en-Laye), Service de médecine interne [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bretonneau, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AP-HP Hôpital universitaire Robert-Debré [Paris], Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de rhumatologie (Hôpitaux Civils de Colmar), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de rhumatologie [CH Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Chimie Agro-Industrielle (CAI), Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'immuno-rhumatologie[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, CHU Trousseau [Tours], Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie[Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier de Dax, Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Joseph Ducuing - Varsovie [Toulouse] (HJD), Hôpitaux Privés de Metz (HPMetz), Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de médecine interne [Centre hospitalier Lons le Saunier], Centre hospitalier Lons le Saunier, Service de Rhumatologie [CHU de Grenoble], Hôpital Sud de Grenoble, Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hopital saint louis (LA ROCHELLE - Hôpital Saint Louis), CH La Rochelle, Service de Médecine Interne [AP-HP, CHU Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], CHU Trousseau [APHP], CHU Amiens-Picardie, Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Langues et civilisations à tradition orale (LACITO), Université Sorbonne Nouvelle - Paris 3-Institut National des Langues et Civilisations Orientales (Inalco)-Centre National de la Recherche Scientifique (CNRS), Études Pharmaco-Immunologie (EPI), Université de La Réunion (UR), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique-Hôpitaux de Paris - Espace éthique (AP-HP Espace éthique), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Maison Blanche, CHU Toulouse [Toulouse], Département de Pédiatrie [Rennes] = Paediatrics [Rennes], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Club Rhumatismes et Inflammation, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Arthrites autoimmunes (AA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal Alençon-Mamers (CHICAM), Service de Médecine interne [CH Antibes Juan-Les-Pins], Centre Hospitalier d’Antibes Juan-les-Pins (CH Antibes Juan-Les-Pins), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), CHU Clermont-Ferrand, Université de Lille, Groupe d'Études Remodelage Osseux et bioMatériaux (GEROM), Université d'Angers (UA), Centre Hospitalier Victor Jousselin de Dreux, Hôpital Lariboisière-Fernand-Widal [APHP], Centre Hospitalier de Belfort (Service de Rhumatologie), Oncology, Regional Hospital of Orleans, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Gabriel Montpied [Clermont-Ferrand], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie, CHU Saint-Etienne, Paediatrics, Paediatric Internal Medicine, Rheumatology and Infectious Diseases [Paris], Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant [Paris] (RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Rhumatologie [CHRU Montpellier], Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Histoire, Archéologie et Littératures des mondes chrétiens et musulmans médiévaux (CIHAM), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-École des hautes études en sciences sociales (EHESS)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Columbia University Irving Medical Center (CUIMC), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie, Assistance Publique - Hôpitaux de Marseille (APHM)-Institut du Mouvement et de l'appareil Locomoteur (IML), Service d'Anesthésie réanimation [CHU Tenon], Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 (MABLab (ex-pmoi)), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Hopital Réné Dubos, Laboratoire d'Economie de Dauphine (LEDa), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine interne - hôpital européen Georges-Pompidou, Aix Marseille Université (AMU), Sorbonne Université (SU), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Université de La Réunion - Faculté de Lettres et Sciences humaines (UR FLSH), Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Grenoble Alpes - École supérieure du professorat et de l'éducation - Académie de Grenoble (UGA ESPE Grenoble), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Groupe ENergie Electrique et SYStémique (LAPLACE-GENESYS), LAboratoire PLasma et Conversion d'Energie (LAPLACE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Cabinet Médical de Rhumatologie, Marseille, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Service de dermatologie et allergologie [CHU Tenon], Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier de Mulhouse (Service de Rhumatologie), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), Centre Hospitalier Universitaire de Nice (CHU Nice), FHU 'Integrated center for research in inflammatory diseases - InCREASe', Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Saint-André, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Joseph Ducuing, Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire Navier (NAVIER UMR 8205), École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques (ENSIACET), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, [SDV]Life Sciences [q-bio], communicable diseases, Disease, Logistic regression, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, law, Adrenal Cortex Hormones, Epidemiology, Immunology and Allergy, Medicine, 030212 general & internal medicine, 2. Zero hunger, education.field_of_study, glucocorticoids, Mortality rate, tumor necrosis factors, Intensive care unit, 3. Good health, Hospitalization, Autoinflammatory Disorders, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, biological therapy, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Hypertension, Female, Adult, medicine.medical_specialty, Immunology, Population, imported, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rheumatology, Internal medicine, Rheumatic Diseases, Humans, autoimmune diseases, Obesity, education, 030203 arthritis & rheumatology, business.industry, SARS-CoV-2, COVID-19, business, Body mass index
Abstract: ObjectivesThere is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.MethodsIndividuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate–severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.ResultsOf 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05–1.10), female gender (OR=0.45, 95% CI: 0.25–0.80), body mass index (OR=1.07, 95% CI: 1.02–1.12), hypertension (OR=1.86, 95% CI: 1.01–3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09–3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47–29.62) and rituximab (OR=4.21, 95% CI: 1.61–10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87–2.42) (n=175 each group).ConclusionsIn the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD.Trial registration numberClinicalTrials.gov Registry (NCT04353609).
Published: 2020

120. Revisiting TNF Receptor-Associated Periodic Syndrome (TRAPS): Current Perspectives

Author: Natalie Deuitch, Cornelia Cudrici, and Ivona Aksentijevich
Subjects: 0301 basic medicine, Review, lcsh:Chemistry, Pathogenesis, TNF inhibitors, 0302 clinical medicine, AA amyloidosis, misfolding disease, Molecular Targeted Therapy, Receptor, lcsh:QH301-705.5, Spectroscopy, IL-1inhibitors, Disease Management, General Medicine, Computer Science Applications, Phenotype, Molecular Diagnostic Techniques, TNF receptor associated periodic syndrome, Receptors, Tumor Necrosis Factor, Type I, Tumor necrosis factor alpha, Disease Susceptibility, tumor necrosis factor receptor-associated periodic syndrome (TRAPS), Fever, Catalysis, Proinflammatory cytokine, Inorganic Chemistry, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, Physical and Theoretical Chemistry, Molecular Biology, 030203 arthritis & rheumatology, business.industry, Organic Chemistry, Hereditary Autoinflammatory Diseases, Genetic Variation, medicine.disease, Autoinflammatory Syndrome, TNFR1, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Immunology, autoinflammatory disorders, Tumor necrosis factor receptor 1, business, Biomarkers
Abstract: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory syndrome characterized by prolonged and recurrent episodes of fever, abdominal and/or chest pain, arthralgia, myalgia, and erythematous rash. TRAPS is associated with heterozygous variants in the TNFRSF1A gene, which encodes the TNFR1 (tumor necrosis factor receptor 1) receptor. Disease-causing variants are found exclusively in the extracellular domain of TNFR1 and affect receptor structure and binding to the TNF ligand. The precise mechanism of the disease is still unclear, but it is thought that intracellular accumulation of misfolded mutant protein leads to endoplasmic reticulum stress and enhanced inflammatory responses through constitutive activation of various immune pathways. Other possible mechanisms contributing to the disease pathogenesis include defective receptor shedding, TNF-induced cell death, production of reactive oxygen species, and autophagy impairment. Patients’ leucocytes are hyperresponsive to stimulation and produce elevated levels of proinflammatory cytokines. Systemic autoimmune (AA) amyloidosis is an important cause of morbidity and mortality in TRAPS. Over the last two decades, new therapies have changed the progression and outcome of the disease. In this review, we summarize clinical data from 209 patients with validated pathogenic variants reported in the literature and discuss TRAPS diagnosis, pathogenesis, and treatment options.
Published: 2020

121. The systemic autoinflammatory disorders for dermatologists. Part 2: disease examples

Author: J. Oldham and Helen J. Lachmann
Subjects: medicine.medical_specialty, Fever, Dermatology, Disease, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), AA amyloidosis, Periodic fever, medicine, Humans, Intensive care medicine, Schnitzler Syndrome, Inflammation, Biological Products, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Hereditary Autoinflammatory Diseases, Receptors, Interleukin-1, Skin Diseases, Genetic, Amyloidosis, medicine.disease, Receptors, Interleukin-6, Cryopyrin-Associated Periodic Syndromes, Immunity, Innate, Tubulin Modulators, Familial Mediterranean Fever, Interleukin 1 Receptor Antagonist Protein, Immune System Diseases, 030220 oncology & carcinogenesis, Steroids, Mevalonate Kinase Deficiency, business, Colchicine, Autoinflammatory Disorders, Dermatologists, Interleukin-1
Abstract: Summary The systemic autoinflammatory disorders (SAIDS) or periodic fever syndromes are disorders of innate immunity, which can be inherited or acquired. They are almost all very rare and easily overlooked; typically, patients will have seen multiple specialities prior to diagnosis, so a high level of clinical suspicion is key. It is important to note that these are ‘high-value’ diagnoses as the majority of these syndromes can be very effectively controlled, dramatically improving quality of life and providing protection against the development of irreversible complications such as AA amyloidosis. In Part 1 of this review, we took an overview of SAIDS and described the common features; in this article, we take a more in-depth look at the better recognized or more dermatologically relevant conditions.
Published: 2020

122. Autoinflammatory Disorders with Perinatal Onset

Author: Nissim G. Stolberg and James W. Verbsky
Subjects: medicine.medical_specialty, Genotype, Inflammation, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Neonatal Screening, Rare Diseases, 030225 pediatrics, medicine, Humans, 030212 general & internal medicine, Genetic Testing, Autoimmune disease, business.industry, fungi, Infant, Newborn, food and beverages, Obstetrics and Gynecology, medicine.disease, Dermatology, Rash, Pathophysiology, Pediatrics, Perinatology and Child Health, medicine.symptom, business, Perinatal period, Autoinflammatory Disorders
Abstract: Autoinflammatory disorders are rare genetic defects that result in inflammation in the absence of an infectious or autoimmune disease. Although very rare, these disorders can occur in the perinatal period, and recognizing their presentation is important because there are often long-term complications and effective targeted therapies for these disorders. Most of these disorders present with rash, fevers, and laboratory evidence of inflammation. Importantly, these disorders can now be separated into their pathophysiologic mechanisms of action, which can also guide therapies. The article reviews the different mechanisms of autoinflammatory disorders and highlights those disorders that can present in the newborn period.
Published: 2020

123. Autoinflammatory Diseases in the Geriatric Population

Author: Merav Lidar and Michal Brodavka
Subjects: Innate immune system, business.industry, Geriatric population, Amyloidosis, Immunology, Recurrent inflammation, Autoantibody, Medicine, business, Complication, medicine.disease, Autoinflammatory Disorders
Abstract: Autoinflammatory disorders are inherited diseases of innate immunity leading to uncontrolled activation of the interleukin-1 pathway. The disorders are characterized by unprovoked recurrent inflammation affecting primarily the skin, as well as the serosal and synovial membranes. As innate immunity is the culprit, there are no autoantibodies or autoreactive T-cells to aid in the diagnosis and reactive amyloidosis is a potential severe long-term complication [1, 2].
Published: 2020

124. Overview of the rarest causes of fever in newborns: handy hints for the neonatologist

Author: Maria Coppola, Domenico Umberto De Rose, Giovanni Vento, Francesca Gallini, Luca Maggio, and Donato Rigante
Subjects: fever, medicine.medical_specialty, Hemophagocytic lymphohistiocytosis, Pediatrics, Mevalonate kinase deficiency, business.industry, Infant, Newborn, Obstetrics and Gynecology, Disease, Neonatal age, medicine.disease, OTULIPENIA, Neonatologists, organ-specific sterile inflammatory manifestations, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Pediatrics, Perinatology and Child Health, medicine, Humans, Kawasaki disease, autoinflammatory disorders, Neonatology, business, Blau syndrome
Abstract: Neonatal causes of fever are a major source of concern for clinicians. If fever is combined with organ-specific sterile inflammatory manifestations the suspicion of autoinflammatory disorders should be considered, and the list of such conditions starting in the neonatal period includes chronic infantile neurological cutaneous articular syndrome, mevalonate kinase deficiency, deficiency of the interleukin-1 receptor antagonist, otulipenia, STING-associated vasculopathy with onset in infancy and Blau syndrome. Other causes of noninfectious fever that can rarely occur in newborns are Kawasaki disease, Behcet's disease, and hemophagocytic lymphohistiocytosis. Diagnosis of these exceptionally rare disorders is challenging for neonatologists. An early recognition of these complex diseases might lead to use more specific or rational drugs preventing permanent consequences. This review focuses on the rarest causes of fever occurring in the neonatal age with the aim of portraying many protean clinical pictures associated with fever and reviewing the potential available treatments.
Published: 2020

125. A relapsing localized variant of neutrophilic dermatosis triggered by tissue injury

Author: Luca Borradori, Christoph Schlapbach, Laurence Feldmeyer, D Wallach, A.D. Gloor, and Anna Rammlmair
Subjects: medicine.medical_specialty, business.industry, Neutrophils, Dermatitis, Dermatology, Sweet Syndrome, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Neutrophilic dermatosis, medicine, Humans, Leukocyte disorder, business, 610 Medicine & health, Autoinflammatory Disorders, Leukocyte Disorders
Abstract: Neutrophilc dermatoses (ND) comprises a group of autoinflammatory disorders characterized by a neutrophilic-rich infiltrate in the skin. Based on their frequent overlapping features ND have been classified into three major groups: (1) superficial ND; (2) dermal ND, and (3) deep ND.1,2 ND are often associated with haematological malignancies and chronic inflammatory diseases.1,2 We report a striking localized form of relapsing ND.
Published: 2020
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126. Emerging insights on the role of gasdermins in infection and inflammatory diseases

Author: Guangjuan Zheng, Chuanjian Lu, Lipeng Tang, and Boudewijn M.T. Burgering
Subjects: 0301 basic medicine, rheumatoid arthritis, lcsh:Immunologic diseases. Allergy, Programmed cell death, Immunology, Reviews, Review, multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Gasdermins, inflammatory bowel disease, Immunology and Allergy, Medicine, General Nursing, Autoimmune disease, Innate immune system, Antitumor immunity, business.industry, Effector, pyroptosis, Pyroptosis, NETosis, medicine.disease, 030104 developmental biology, Lytic cycle, business, lcsh:RC581-607, Autoinflammatory Disorders, 030215 immunology
Abstract: The gasdermins, family of pore‐forming proteins, are emerging key regulators of infection, autoinflammation and antitumor immunity. Multiple studies have recently characterised their crucial roles in driving pyroptosis, a lytic pro‐inflammatory type of cell death. Additionally, gasdermins also act as key effectors of NETosis, secondary necrosis and apoptosis. In this review, we will address current understanding of the mechanisms of gasdermin activation and further describe the protective and detrimental roles of gasdermins in host defence and autoinflammatory diseases. These data suggest that gasdermins play a prominent role in innate immunity and autoinflammatory disorders, thereby providing potential new therapeutic avenues for the treatment of infection and autoimmune disease., This review summarises the latest advances in several aspects of mode of activation of gasdermins, which finally drives pyroptosis, NETosis, secondary necrotic death and apoptosis. Here, we also highlight the current understanding of gasdermin involvement in infections and autoimmunity disorders, providing a promising translational approach to the treatment of infectious and autoinflammatory diseases.
Published: 2020

127. Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee

Author: Capucine Picard, Kathleen E. Sullivan, Hans D. Ochs, Charlotte Cunningham-Rundles, Aziz Bousfiha, Christoph Klein, Waleed Al-Herz, Jennifer M. Puck, Amos Etzioni, Troy R. Torgerson, Jean-Laurent Casanova, Stuart G. Tangye, Steven M. Holland, Eric Oksenhendler, José Luis Franco, Talal A. Chatila, and Tomohiro Morio
Subjects: 0301 basic medicine, inborn errors of immunity, Immunology, Computational biology, Disease, Expert committee, primary immune deficiency, Novel gene, 03 medical and health sciences, 0302 clinical medicine, Rare Diseases, Immunity, immune dysregulation, Genetics, Immunology and Allergy, Medicine, 2.1 Biological and endogenous factors, Aetiology, Pediatric, business.industry, Inflammatory and immune system, IUIS, 3. Good health, Rapid identification, 030104 developmental biology, Good Health and Well Being, Original Article, autoinflammatory disorders, next-generation sequencing, business, Autoinflammatory Disorders, 030215 immunology
Abstract: We report the updated classification of Inborn Errors of Immunity/Primary Immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 430 inborn errors of immunity, including 64 gene defects that have either been discovered in the past 2 years since the previous update (published January 2018) or were characterized earlier but have since been confirmed or expanded upon in subsequent studies. The application of next-generation sequencing continues to expedite the rapid identification of novel gene defects, rare or common; broaden the immunological and clinical phenotypes of conditions arising from known gene defects and even known variants; and implement gene-specific therapies. These advances are contributing to greater understanding of the molecular, cellular, and immunological mechanisms of disease, thereby enhancing immunological knowledge while improving the management of patients and their families. This report serves as a valuable resource for the molecular diagnosis of individuals with heritable immunological disorders and also for the scientific dissection of cellular and molecular mechanisms underlying inborn errors of immunity and related human diseases.
Published: 2020

128. Autoinflammatory Disorders Showing Pernio-like Eruptions

Author: Nobuo Kanazawa and Tomoyuki Hara
Subjects: medicine.medical_specialty, medicine, Dermatology, Autoinflammatory Disorders
Published: 2018

129. Disease modeling of immunological disorders using induced pluripotent stem cells

Author: Megumu K. Saito
Subjects: 0301 basic medicine, Mechanism (biology), Immunology, Disease, Biology, In vitro, 03 medical and health sciences, Haematopoiesis, 030104 developmental biology, 0302 clinical medicine, Immune system, 030220 oncology & carcinogenesis, Cancer research, Immunology and Allergy, Genetic diagnosis, Induced pluripotent stem cell, Autoinflammatory Disorders
Abstract: Disease-associated induced pluripotent stem cells (iPSCs) established from patients are now widely used for disease modeling. They can provide an unlimited source of hematopoietic cells that carry the patients' genetic background, making them advantageous for modeling immunological disorders. To obtain functional immune cells from human iPSCs, we have developed a differentiation system that generates immortalized myeloid cells including neutrophils and monocytic cells. By using this strategy, we have established in vitro models of many immunological disorders. In this review, we focus on autoinflammatory disorders. These models have proven useful for genetic diagnosis and elucidation of the disease mechanism.
Published: 2018

130. Update on Autoinflammatory Syndromes

Author: Danielle C Fair and James W. Verbsky
Subjects: business.industry, Mechanism (biology), Disease mechanisms, medicine, Inflammasome, General Medicine, business, Neuroscience, Autoinflammatory Disorders, medicine.drug
Abstract: Advances in genetic techniques have led to the discovery of new autoinflammatory syndromes in the last three years. The purpose of this review is to discuss novel autoinflammatory syndromes including disease mechanisms, characteristics, and treatments. We will also discuss recent findings regarding the pathophysiology of well-known autoinflammatory disorders. Several recently described autoinflammatory disorders will be discussed including NLRC4-MAS, NAIAD, CANDLE, SAVI, ORAS, HA20, DADA2, and APLAID. There is now a better understanding of the pathophysiology of autoinflammatory disorders that has allowed for categorization of these disorders into interferonopathies, inflammasome mediated, or NF-κB dysregulated. With a better understanding of these disorders, targeted treatments based on their mechanism are now possible. Some of these disorders have an unknown mechanism of action, and novel disorders are likely. Further research on autoinflammatory disorders is necessary to improve the outcomes of these patients.
Published: 2018

131. Function and regulation of IL-1α in inflammatory diseases and cancer

Author: Ankit Malik and Thirumala-Devi Kanneganti
Subjects: 0301 basic medicine, Inflammasomes, Interleukin-1beta, Immunology, Inflammation, Biology, Bioinformatics, Article, Autoimmune Diseases, 03 medical and health sciences, Interleukin-1alpha, Neoplasms, medicine, Animals, Humans, Immunology and Allergy, Receptor, Receptors, Interleukin-1, Cancer, Interleukin, medicine.disease, 030104 developmental biology, medicine.symptom, Autoinflammatory Disorders, Biogenesis, Function (biology), Signal Transduction
Abstract: The interleukin (IL)-1 family of cytokines is currently comprised of 11 members that have pleiotropic functions in inflammation and cancer. IL-1α and IL-1β were the first members of the IL-1 family to be described, and both signal via the same receptor, IL-1R. Over the last decade, much progress has been made in our understanding of biogenesis of IL-1β and its functions in human diseases. Studies from our laboratory and others have highlighted the critical role of nod-like receptors (NLRs) and multi-protein complexes known as inflammasomes in the regulation of IL-1β maturation. Recent studies have increased our appreciation of the role played by IL-1α in inflammatory diseases and cancer. However, the mechanisms that regulate the production of IL-1α and its bioavailability are relatively understudied. In this review, we summarize the distinctive roles played by IL-1α in inflammatory diseases and cancer. We also discuss our current knowledge about the mechanisms that control IL-1α biogenesis and activity, and the major unanswered questions in its biology.
Published: 2017

132. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity

Author: Capucine Picard, Mimi L.K. Tang, Jean-Laurent Casanova, Amos Etzioni, José Luis Franco, Charlotte Cunningham-Rundles, Tomohiro Morio, Christoph Klein, Yanick J. Crow, Waleed Al-Herz, Kathleen E. Sullivan, Aziz Bousfiha, Steven M. Holland, Jennifer M. Puck, H. Bobby Gaspar, Hans D. Ochs, Stuart G. Tangye, Talal A. Chatila, Troy R. Torgerson, and Eric Oksenhendler
Subjects: Societies, Scientific, Research Report, 0301 basic medicine, medicine.medical_specialty, Immunology, World Health Organization, World health, primary immune deficiency, 03 medical and health sciences, immune dysregulation, Committee report, Allergy and Immunology, Political science, medicine, Humans, Immunology and Allergy, Inflammatory and immune system, Immunologic Deficiency Syndromes, Immunity, Scientific, IUIS, medicine.disease, 3. Good health, 030104 developmental biology, Family medicine, Primary immunodeficiency, Original Article, autoinflammatory disorders, Societies, Autoinflammatory Disorders
Abstract: Beginning in 1970, a committee was constituted under the auspices of the World Health Organization (WHO) to catalog primary immunodeficiencies. Twenty years later, the International Union of Immunological Societies (IUIS) took the remit of this committee. The current report details the categorization and listing of 354 (as of February 2017) inborn errors of immunity. The growth and increasing complexity of the field have been impressive, encompassing an increasing variety of conditions, and the classification described here will serve as a critical reference for immunologists and researchers worldwide.
Published: 2017

133. Inflammasome and cytokine blocking strategies in autoinflammatory disorders.

Author: Moll, Monika and Kuemmerle-Deschner, Jasmin B.
Subjects: *INFLAMMATION, *AUTOIMMUNE diseases, *CYTOKINES, *DISEASE relapse, *NATURAL immunity, *GENETIC disorders
Abstract: Abstract: Autoinflammatory disorders are characterized by usually unprovoked recurrent episodes of features of inflammation caused by activation of the innate immune system. Many autoinflammatory disorders – the monogenetic defects in particular – are associated with alterations of inflammasomes. Inflammasomes are complex multimolecular structures, which respond to “danger” signals by activation of cytokines. Among these, IL-1 is the key player of the innate immune response and inflammation. Consequently, IL-1 blocking strategies are specific pathway targeting therapies in autoinflammatory diseases and applied in CAPS, colchicine-resistant FMF, TRAPS, HIDS and DIRA. A number of rare genetic disorders involve inflammasome malfunction resulting in enhanced inflammatory response. IL-1 inhibition to date is the most successful specific therapy in autoinflammatory disorders. Here, current treatment strategies in autoinflammatory disorders are reviewed with a focus on inflammasome and cytokine inhibition. [Copyright &y& Elsevier]
Published: 2013
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134. Primary immunodeficiencies: A rapidly evolving story.

Author: Parvaneh, Nima, Casanova, Jean-Laurent, Notarangelo, Luigi Daniele, and Conley, Mary Ellen
Subjects: IMMUNODEFICIENCY, IMMUNE response, HUMAN herpesvirus-6, HERPES simplex virus, T-cell receptor genes, TOLL-like receptors
Abstract: The characterization of primary immunodeficiencies (PIDs) in human subjects is crucial for a better understanding of the biology of the immune response. New achievements in this field have been possible in light of collaborative studies; attention paid to new phenotypes, infectious and otherwise; improved immunologic techniques; and use of exome sequencing technology. The International Union of Immunological Societies Expert Committee on PIDs recently reported on the updated classification of PIDs. However, new PIDs are being discovered at an ever-increasing rate. A series of 19 novel primary defects of immunity that have been discovered after release of the International Union of Immunological Societies report are discussed here. These new findings highlight the molecular pathways that are associated with clinical phenotypes and suggest potential therapies for affected patients. [Copyright &y& Elsevier]
Published: 2013
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135. Role of Autoimmunity and Autoinflammation in the Pathogenesis of Idiopathic Recurrent Pericarditis.

Author: Cantarini, Luca, Imazio, Massimo, Brizi, Maria, Lucherini, Orso, Brucato, Antonio, Cimaz, Rolando, and Galeazzi, Mauro
Abstract: Idiopathic recurrent pericarditis is the most common and troublesome complication of acute pericarditis affecting about one third of such patients. The pericardium may be involved in different systemic autoimmune diseases (i.e., systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, mixed connective tissue disease, Sjogren's Syndrome, polyarteritis, giant cell arteritis, other systemic vasculitides) either in a symptomatic form (usually during the active phase of the disease) or as asymptomatic pericardial effusion. Moreover, idiopathic recurrent pericarditis mimicks hereditary periodic fever syndromes (HPFSs). HPFSs are a group of disorders characterized by primary dysfunction of the innate immune system mostly caused by mutations of genes involved in the regulation or activation of the inflammatory response, without any apparent involvement of antigen-specific T cells or significant production of autoantibodies. These disorders usually manifest in the pediatric population, with onset ranging from the first hours to the first decade of life, however a limited number of patients experience disease onset during adulthood. [ABSTRACT FROM AUTHOR]
Published: 2013
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136. Rhumatisme palindromique

Author: Vayssade, M., Tatar, Z., and Soubrier, M.
Subjects: *PALINDROMIC DNA, *RHEUMATISM, *RHEUMATOID arthritis, *FAMILIAL Mediterranean fever, *GENETIC mutation, *CONNECTIVE tissue diseases
Abstract: Abstract: Palindromic rheumatism is characterized by episodes of arthritis or para-arthritis leaving no residual or radiographic changes. Several diseases should be ruled out in the differential diagnosis. Evolution to rheumatoid arthritis is common, especially in patient with positive rheumatoid factor and anticitrullinated peptides. In seronegative patients, palindromic rheumatism could be part of the spectrum of autoinflammatory diseases because of a high frequency of MEFV mutations. Treatment remains discussed. The use of antimalarials could delay the development of rheumatoid arthritis or another connective tissue disease. [Copyright &y& Elsevier]
Published: 2013
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137. Tumour necrosis factor receptor-associated periodic syndrome (TRAPS): State of the art and future perspectives

Author: Cantarini, Luca, Lucherini, Orso Maria, Muscari, Isabella, Frediani, Bruno, Galeazzi, Mauro, Brizi, Maria Giuseppina, Simonini, Gabriele, and Cimaz, Rolando
Subjects: *TUMOR necrosis factor receptors, *IMMUNOLOGY of inflammation, *ABDOMINAL pain, *JOINT pain, *MYALGIA, *FEVER
Abstract: Abstract: Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory disorder characterized by periodic fever episodes, arthralgia, myalgia, abdominal pain, serositis, and skin rash. TRAPS is caused by mutations in the gene encoding the TNF Receptor Super Family 1A (TNFRSF1A) on chromosome 12p13. The identification of TNFRSF1A mutations as the genetic cause of TRAPS coincided with the wider use of biological agents in medicine and raised the possibility that blocking TNF could potentially represent the primary therapeutic goal in TRAPS, thus disclosing new treatment choices for this complex disease. Anti-TNF therapy in TRAPS has been based on etanercept, a recombinant human TNFR (p75)-Fc fusion protein comprising two receptors linked by an IgG1 Fc fragment. However a decrease in responsiveness to etanercept over time has been described, and it may be due to a non-specific action of etanercept in TRAPS; its efficacy may reflect ‘generic’ anti-inflammatory properties. Long-term adherence to etanercept is poor and a significant number of patients need to switch to anti-interleukin (IL)-1β therapy. In fact, the IL-1 receptor antagonist anakinra has recently been shown to prevent disease relapses both in the short- and in the long-term, and to induce a prompt and stable disease remission. [Copyright &y& Elsevier]
Published: 2012
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138. The diagnostic evaluation of patients with potential adult-onset autoinflammatory disorders: Our experience and review of the literature

Author: Muscari, Isabella, Iacoponi, Francesca, Cantarini, Luca, Lucherini, Orso Maria, Simonini, Gabriele, Brizi, Maria Giuseppina, Vitale, Antonio, Frediani, Bruno, Cimaz, Rolando, and Galeazzi, Mauro
Subjects: *INFLAMMATION, *LITERATURE reviews, *GENETIC disorders, *GENETIC mutation, *IMMUNE system, *NATURAL immunity, *DIAGNOSIS
Abstract: Abstract: Hereditary periodic fever syndromes (HPFSs) are a group of inherited disorders of the innate immune system caused by mutations of genes involved in the regulation or activation of the inflammatory response, which belong to the category of autoinflammatory disorders. Most HPFs typically have an onset in pediatric age, while a limited number of patients experience disease onset during adulthood. The relative rarity and lack of information on adult-onset autoinflammatory diseases make it likely that genetic testing is often inconclusive. Recently, we have identified a set of variables related to the probability of detecting gene mutations in MEFV, responsible for familial Mediterranean fever, and TNFRSF1A, responsible for tumor necrosis factor receptor-associated periodic syndrome. In addition, we have proposed a diagnostic score for identifying those patients at high risk of carrying mutations in these genes. However, before the score can be recommended for application, further evaluation by means of longitudinal studies on different ethnicities and different populations deriving from other geographical areas is needed in order to definitively verify both its sensitivity and its specificity. The present manuscript offers our suggestions on how to establish a differential diagnosis for adult-onset HPFs, as well as a review of the literature, and we also provide a score revision available online. [Copyright &y& Elsevier]
Published: 2012
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139. Definition of primary immunodeficiency in 2011: a 'trialogue' among friends.

Author: Conley, Mary Ellen, Notarangelo, Luigi D., and Casanova, Jean‐Laurent
Subjects: *IMMUNODEFICIENCY, *NATURAL immunity, *GENETIC disorders, *PHENOTYPES, *INBORN errors of metabolism, *POPULATION genetics, *IMMUNE system
Abstract: There is no clear consensus about the definition of the term primary immunodeficiency in 2011. Although there is general agreement that defects in both adaptive and innate immunity should be included, issues related to the frequency of primary immunodeficiencies, the modes of inheritance, the other types of cells involved, and the required clinical phenotype are more contentious. Three friends with an interest in both the clinical and scientific aspects of primary immunodeficiency carried out a discussion or trialogue to address some of these issues. [ABSTRACT FROM AUTHOR]
Published: 2011
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140. Documento de Consenso de la Sociedad de Infectología Pediatrica y la Sociedad de Reumatología Pediatrica sobre el diagnóstico diferencial y el abordaje terapéutico de la fiebre recurrente.

Author: Calvo Rey, C., Soler-Palacín, P., Merino Muñoz, R., Saavedra Lozano, J., Antón López, J., Aróstegui, J. I., Blázquez Gamero, D., Martín-Nalda, A., Juan, M., Méndez, M., Piñeiro Perez, R., and Calvo, I.
Published: 2011
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141. Cytophagic histiocytic panniculitis and hemophagocytic lymphohistiocytosis: an overview.

Author: Aronson, Iris K. and Worobec, Sophie M.
Subjects: *ADIPOSE tissue diseases, *INFLAMMATION, *MACROPHAGES, *T cells, *LYMPHOMAS, *INTERLEUKIN-1
Abstract: Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis that is associated with systemic features including fevers, hepatosplenomegaly, lymphadenopathy, pancytopenia, hepatic abnormalities, hypertriglyceridemia, and coagulopathy without an elevated erythrocyte sedimentation rate. The panniculitis lesions show adipose tissue lymphocytic and histiocytic infiltration along with hemophagocytosis, which may also appear in bone marrow, spleen, lymph nodes, and liver. Patients may have a rapidly fatal disease course, a longer disease course with intermittent remissions and exacerbations for many years prior to death, or a nonfatal acute or intermittent course responsive to treatment. The cytophagocytic disorder in these patients is a hemophagocytic lymphohistiocytosis (HLH), similar to the infection-activated reaction associated with perforin mutations found in familial hemophagocytic lymphohistiocytosis. HLH is a group of autoinflammatory disorders, which include macrophage activation syndrome and infection-associated hemophagocytic syndrome, which if not treated rapidly, can be fatal. The relationship of CHP and HLH is discussed. CHP associated diseases include: subcutaneous panniculitis-like T cell lymphomas; infections, connective tissue diseases, other malignancies, and the molecular disorders that cause HLH. Treatment of CHP includes: glucocorticoids in combination with cyclosporine, combined chemotherapeutic medications and most recently, anakinra, an Interleukin-1 receptor antagonist; along with supportive care, search for underlying malignancies and treatment thereof, and control of associated infections. [ABSTRACT FROM AUTHOR]
Published: 2010
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142. Long-term safety and effectiveness of canakinumab therapy in patients with cryopyrin-associated periodic syndrome: results from the β-Confident Registry

Author: Stephanie Noviello, Eleni Vritzali, Jeremy Levy, Philip N. Hawkins, Ulrich A. Walker, Tom van der Poll, Hugh H. Tilson, Jasmin B Kuemmerle-Deschner, Hal M. Hoffman, Center of Experimental and Molecular Medicine, Infectious diseases, and AII - Inflammatory diseases
Subjects: Adult, medicine.medical_specialty, cryopyrin-associated periodic syndromes, Immunology, Disease, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Familial Cold Autoinflammatory Syndrome, Informed consent, Internal medicine, medicine, Rectal Adenocarcinoma, Humans, Immunology and Allergy, In patient, Registries, 030212 general & internal medicine, Adverse effect, 030203 arthritis & rheumatology, business.industry, Antibodies, Monoclonal, Cryopyrin-associated periodic syndrome, medicine.disease, Autoinflammatory Disorders, Canakinumab, biological therapy, inflammation, Medicine, business, medicine.drug
Abstract: ObjectiveTo report the long-term safety and effectiveness of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and neonatal-onset multisystem inflammatory disease (NOMID), in a real-world setting.MethodsFrom December 2009 to December 2015, the β-Confident Registry prospectively enrolled patients with CAPS and non-CAPS conditions who received canakinumab per routine care and were prospectively followed for up to 6 years. The registry protocol did not mandate specific visits or procedures; however, all observed adverse events (AEs) and serious adverse events (SAEs) had to be recorded. Canakinumab effectiveness was evaluated by Physician’s Global Assessment (PGA).ResultsOf 288 patients enrolled, 3 were excluded due to missing informed consent. Among the remaining 285 patients, 243 (85.3%) were patients with CAPS and 42 (14.7%) had atypical CAPS (6.3%) or other conditions (8.4%). The median age was 26.6 years. Based on PGA, 58 of 123 (47.2%) patients with CAPS had no disease activity at 48 months, and 65 of 123 (52.8%) experienced mild/moderate disease activity at 48 months. Among CAPS phenotypes, AE incidence rates per 100 patient-years were lowest for FCAS (73.1; 95% CI 60.3 to 87.8) compared with those with MWS (105.0; 95% CI 97.2 to 113.2) or NOMID (104.6; 95% CI 86.6 to 125.2). One hundred twenty-eight SAEs were reported in 68 patients with CAPS (incidence rate/100 patient-years, 14.0; 95% CI 11.6 to 16.6). One death (metastatic rectal adenocarcinoma in a patient with MWS) was reported.ConclusionsThe response to canakinumab was sustained for up to 6 years. Canakinumab demonstrated a favourable safety profile over long-term treatment in patients with CAPS.Trial registration numberNCT01213641.
Published: 2021

143. Quoi de neuf dans les maladies auto-inflammatoires ?

Author: Stankovic, K. and Grateau, G.
Subjects: *GENETIC disorders, *INFLAMMATION, *NATURAL immunity, *NOSOLOGY, *INTERLEUKIN-1, *PROTEINS
Abstract: Abstract: Purpose: The concept of auto-inflammation was initially coined to define the group of mendelian disorders characterized by recurrent inflammatory symptoms. The core of this group mainly consists of hereditary recurrent fevers, which has been lately enlarged to other inflammatory mendelian disorders as well as to some sporadic diseases with a genetic component relevant to innate immunity. Current knowledge and key points: Cryopyrin, the product of the CIAS1/PYPPAF1/NALP3/NLRP gene, whose mutations underline some mendelian syndromes (Mückle-Wells and chronic infantile neurological cutaneous and articular (CINCA), familial cold urticaria) can now be considered as a major factor of the regulation of interleukin-1 production within the multiprotein complex called inflammasome. This discovery has lit up our view of innate immunity. Future prospects and projects: The contribution of the innate immunity mechanisms in inflammatory disorders have led to a new look to the current nosology of this vast group of diseases and to suggest a classification with two poles. The first would be defined by the predominance of auto-inflammation, whereas in the second one auto-immunity predominates. [Copyright &y& Elsevier]
Published: 2008
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144. Insight into the inflammasome and caspase-activating mechanisms.

Author: Gaide, Olivier and Hoffman, Hal M.
Subjects: CYTOKINES, IMMUNOREGULATION, GENETICS, GENETIC mutation, THERAPEUTICS, ULTRAVIOLET radiation
Abstract: Inflammasomes are recently discovered molecular complexes that can sense danger signals and specifically activate caspase-1 and -5 and proinflammatory cytokines (IL-1β and IL-18). Upon signaling, the inflammasome complex forms around a NOD-like receptor family member that serves both as a danger sensor and as a recruiting platform. The number of known triggers that stimulate inflammasomes is rapidly rising, ranging from genetic mutations to microbial products, gout crystals, ultraviolet light and adjuvant chemicals. As a result of this surprising diversity, the inflammasome may have a significant impact on most medical fields. A good understanding of the molecular mechanisms underlying its activation/regulation is essential today, as several therapeutic and diagnostic tools have already reached the bedside, and more are sure to come. [ABSTRACT FROM AUTHOR]
Published: 2008
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145. A Four-Year-Old Boy With Fever, Rash, and Arthritis.

Author: Mathes, Erin F.D. and Gilliam, Amy E.
Subjects: HOSPITAL care of children, CUTANEOUS tuberculosis, AGE distribution, PEDIATRIC dermatology
Abstract: The triad of fever, rash, and arthritis in a hospitalized child suggests an inflammatory, infectious, or postinfectious process in most cases; however, malignancy must be considered. The most common causes in this age group are inflammatory conditions, including Kawasaki disease, Henoch-Schönlein Purpura, serum sickness-like reaction, and juvenile idiopathic arthritis. Other rarer inflammatory processes can present with this triad of symptoms such as Cryopyrin-related diseases (autoinflammatory disorders), urticarial vasculitis, and systemic lupus erythematosus. We will discuss the differential diagnosis and inpatient management of fever, rash, and arthritis in a young child, focusing on inflammatory conditions. The important features which can help distinguish these conditions include the nature of the rash, associated signs or symptoms, time course of the eruption, and characteristic laboratory and/or histologic findings. [Copyright &y& Elsevier]
Published: 2007
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146. Geoepidemiology and Immunologic Features of Autoinflammatory Diseases: a Comprehensive Review

Author: Thierry Walzer, Sarah Benezech, Yvan Jamilloux, Mathieu Gerfaud-Valentin, Alexandre Belot, Flora Magnotti, Pascal Sève, Emilie Bourdonnay, Thomas Henry, Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Interne [Hôpital Croix Rousse, CHU Lyon], CHU Lyon-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Familial Mediterranean fever, Autoimmunity, Computational biology, Disease, Pyrin domain, OTULIPENIA, 03 medical and health sciences, 0302 clinical medicine, Humans, Immunology and Allergy, Medicine, Immunodeficiency, Inflammation, 030203 arthritis & rheumatology, business.industry, Mechanism (biology), Immunologic Deficiency Syndromes, General Medicine, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030104 developmental biology, Immune System Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Gene-Environment Interaction, business, Signalling pathways, Autoinflammatory Disorders, Signal Transduction
Abstract: International audience; The knowledge on systemic autoinflammatory disorders (SAID) is expanding rapidly and new signalling pathways are being decrypted. The concept of autoinflammation has been proposed since 1999, to define a group of diseases with abnormal innate immunity activation. Since then, more than 30 monogenic SAID have been described. In this review, we first describe inflammasomopathies and SAID related to the interleukin-1 pathway. Recent insights into the pathogenesis of familial Mediterranean fever and the function of Pyrin are detailed. In addition, complex or polygenic SAID, such as Still’s disease or PFAPA syndrome, are also discussed. Then, major players driving autoinflammation, such as type-1 interferonopathies (including the recently described haploinsuffiency in A20 and otulipenia), TNF-associated periodic syndromes, defects in ubiquitination, and SAID with overlapping features of autoimmunity or immunodeficiency. Discoveries of the pathogenic role of mosaicism, intronic defects coupled to the likelihood to identify digenic or polygenic diseases are providing new challenges for physicians and geneticists. This comprehensive review depicts the various SAID, presenting them according to their predominant pathophysiological mechanism, with a particular emphasis on recent findings. Epidemiologic data are also presented. Finally, we propose a practical diagnostic approach to the most common monogenic SAID, based on the most characteristic clinical presentation of these disorders.
Published: 2017

147. When to Suspect Autoinflammatory/Recurrent Fever Syndromes

Author: James W. Verbsky
Subjects: 0301 basic medicine, Delayed Diagnosis, Fever, Arthritis, Inflammation, Systemic inflammation, Diagnosis, Differential, 03 medical and health sciences, Rare Diseases, 0302 clinical medicine, Recurrence, Humans, Medicine, Diagnostic Errors, Child, 030203 arthritis & rheumatology, Innate immune system, business.industry, Hereditary Autoinflammatory Diseases, Syndrome, medicine.disease, Rash, Immunity, Innate, 030104 developmental biology, Recurrent fever, Pediatrics, Perinatology and Child Health, Immunology, medicine.symptom, business, Autoinflammatory Disorders
Abstract: Autoinflammatory disorders are disorders characterized by rash, arthritis, fever, and systemic inflammation. These disorders are caused by mutations in genes important in innate immune system sensors. This review highlights the workup of an individual with recurrent episodes of inflammation, features of these disorders, the genetic defects that cause these disorders, and the specific treatments available.
Published: 2017

148. JAK inhibitors in autoinflammation

Author: Lori Broderick and Hal M. Hoffman
Subjects: Compassionate Use Trials, Male, 0301 basic medicine, Adolescent, Cohort Studies, Young Adult, 03 medical and health sciences, Tnf blockade, Humans, Janus Kinase Inhibitors, Medicine, Prospective Studies, Clinical efficacy, Stat signaling, Child, Inflammation, Sulfonamides, Janus kinase 1, business.industry, Hereditary Autoinflammatory Diseases, Infant, Janus Kinase 1, General Medicine, Janus Kinase 2, Gene signature, Treatment Outcome, 030104 developmental biology, Purines, Child, Preschool, Commentary, Cancer research, Azetidines, Pyrazoles, Female, Interferons, business, Janus kinase, Autoinflammatory Disorders, Rare disease
Abstract: Monogenic IFN-mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN-blocking activity in vitro, to ameliorate disease.Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI (stimulator of IFN genes-associated [STING-associated] vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an expanded access program. The patients underwent dose escalation, and the benefit was assessed by reductions in daily disease symptoms and corticosteroid requirement. Quality of life, organ inflammation, changes in IFN-induced biomarkers, and safety were longitudinally assessed.Eighteen patients were treated for a mean duration of 3.0 years (1.5-4.9 years). The median daily symptom score decreased from 1.3 (interquartile range [IQR], 0.93-1.78) to 0.25 (IQR, 0.1-0.63) (P0.0001). In 14 patients receiving corticosteroids at baseline, daily prednisone doses decreased from 0.44 mg/kg/day (IQR, 0.31-1.09) to 0.11 mg/kg/day (IQR, 0.02-0.24) (P0.01), and 5 of 10 patients with CANDLE achieved lasting clinical remission. The patients' quality of life and height and bone mineral density Z-scores significantly improved, and their IFN biomarkers decreased. Three patients, two of whom had genetically undefined conditions, discontinued treatment because of lack of efficacy, and one CANDLE patient discontinued treatment because of BK viremia and azotemia. The most common adverse events were upper respiratory infections, gastroenteritis, and BK viruria and viremia.Upon baricitinib treatment, clinical manifestations and inflammatory and IFN biomarkers improved in patients with the monogenic interferonopathies CANDLE, SAVI, and other interferonopathies. Monitoring safety and efficacy is important in benefit-risk assessment.ClinicalTrials.gov NCT01724580 and NCT02974595.This research was supported by the Intramural Research Program of the NIH, NIAID, and NIAMS. Baricitinib was provided by Eli Lilly and Company, which is the sponsor of the expanded access program for this drug.
Published: 2018

149. Rare Monogenic Causes of Periodic Fevers

Author: Erkan Demirkaya, Roberta A. Berard, and Serife Gulmus
Subjects: OTULIPENIA, Interleukin 1 receptor antagonist, Treatment modality, business.industry, Immunology, medicine, Inflammation, medicine.symptom, Autoinflammatory Syndrome, Systemic inflammation, business, Autoinflammatory Disorders
Abstract: Autoinflammatory disorders were first recognized nearly two decades ago as unique historical and physical features caused by dysregulation in the innate immune system. Since then, the application of the next-generation sequencing techniques have led to the identification of new monogenic disorders and help to understand the molecular link between disease-causing mutations and inflammation. Most of the newly identified syndromes are characterized by fever episodes and systemic inflammation. Specifically, pediatric rheumatologists are likely to be asked to evaluate patients with periodic or nonperiodic fever syndromes. It is important that they should be aware of the clinical, laboratory characteristics and treatment modalities of these rare autoinflammatory disorders. In this chapter, we review some of these monogenic autoinflammatory diseases, including Behcet-like autoinflammatory syndrome (AISBL), otulipenia, DIRA (deficiency of interleukin 1 receptor antagonist), and DITRA (deficiency of interleukin-36 receptor antagonist). We describe clinical features of these syndromes and further examine their molecular mechanisms and therapeutic options.
Published: 2019

150. Current practices for the genetic diagnosis of autoinflammatory diseases: results of a European Molecular Genetics Quality Network Survey

Author: Simon Patton, Dorota Rowczenio, Isabelle Touitou, Marielle E. van Gijn, Yael Shinar, Isabella Ceccherini, Katie Sheils, University College of London [London] (UCL), The Chaim Sheba Medical Center [Tel Hashomer, Israel], IRCCS Istituto Giannina Gaslini [Genoa, Italy], St. Mary's Research Center, St. Mary's Hospital, University Medical Center [Utrecht], St Mary's Hospital Manchester, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: medicine.medical_specialty, media_common.quotation_subject, Computational biology, Patient care, Article, 03 medical and health sciences, Monogenic autoinflammatory disorders (AIDs), Molecular genetics, Surveys and Questionnaires, External quality assessment, Genetics, medicine, Humans, Hereditary Recurrent Fevers, Quality (business), Genetic Predisposition to Disease, Public Health Surveillance, Genetic Testing, Practice Patterns, Physicians', Genetics (clinical), Genetic Association Studies, media_common, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Next-generation sequencing (NGS), 030305 genetics & heredity, Hereditary Autoinflammatory Diseases, Hereditary recurrent fevers, 3. Good health, Europe, Genetic diagnosis, Identification (biology), business, Autoinflammatory Disorders
Abstract: International audience; Monogenic autoinflammatory disorders (AIDs) are rare diseases caused by variants in genes regulating the innate immune system. The identification of the first four genes responsible for the prototype group of hereditary recurrent fevers prompted the development of genetic diagnosis, followed by external quality assessment and guidelines for the interpretation of sequence variants in these diseases. Recent changes in the diagnosis of genetic diseases, namely the implementation of next-generation sequencing (NGS), lead to discovery of the new genes associated with at least 40 novel AIDs, which revolutionized patient care and prognosis. However, these rapid advances resulted in nonstandardized molecular strategies that can influence genetic diagnosis and reporting of results. In order to assess factors, which may have an impact on performance and quality of results in the NGS era, we carried out an online survey among member laboratories of the European Molecular Genetics Quality Network, which highlighted different strategies being used and identified pitfalls that deserve discussion and improvement.
Published: 2019

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