The Experts below are selected from a list of 729 Experts worldwide ranked by ideXlab platform
Jordi Yague - One of the best experts on this subject based on the ideXlab platform.
-
behcet s disease and Hereditary Periodic Fever syndromes casual association or causal relationship
Clinical and Experimental Rheumatology, 2005Co-Authors: Gerard Espinosa, Juan I Arostegui, Jordi Yague, S Plaza, J Rius, Ricard Cervera, J FontAbstract:Objective. Mutations in the MEFV and the type 1 TNF receptor (TNFRSF 1A) genes have recently been linked to familial Mediterranean Fever (FMF) and TNF receptor-associated Periodic syndrome (TRAPS), respectively. A higher prevalence of Behcet's disease (BD) among FMF patients has been described compared to the general population. The aim of this study was to evaluate whether FMF, TRAPS and BD could be genetically related. Methods. We screened a cohort of 50 BD patients and 100 healthy subjects for the common MEFV and TNFRSF 1A mutations. An initial screening of exons 10 and 2 of the MEFV gene and exon 4 of the TNFRSF 1A was performed in all chromosomes. Results. The heterozygous MEFV imitation (K695R) was found in one (2%) BD patient. Analysis for FMF mutations in the control group revealed that 5 (5%) individuals bore MEFV gene mutations (3 were heterozygous for the E148Q and 2 were heterozygous for the A744S). At codon 202, there were no differences in allele frequencies between BD and control population: 73%R 27%Q in the BD patients vs 75%R 25%Q in controls. Concerning mutations in the TNFRSF IA gene, the R92Q mutation was present in heterozygous state in one (2%) BD patient and in 4 (4%) controls without differences between allele frequencies: 99%R 1%Q in BD patients vs 98%R 2%Q in controls, respectively. There was no association between the clinical manifestations of BD patients and the presence of a particular polymorphism or a mutation. Conclusions. Neither FMF nor TRAPS are genetically associated with BD in our cohort of Spanish patients.
-
etanercept plus colchicine treatment in a child with tumour necrosis factor receptor associated Periodic syndrome abolishes auto inflammatory episodes without normalising the subclinical acute phase response
European Journal of Pediatrics, 2005Co-Authors: Juan I Arostegui, Anna Aldea, Josefa Rius, Jordi Vives, Pilar Solis, Teresa Cantero, Pilar Bahillo, S Plaza, Samuel Gomez, Jordi YagueAbstract:We investigated the cause of Hereditary Periodic Fever syndrome in a Spanish child with recurrent long episodes of Fever, migratory skin rash, myalgia, arthralgia, conjunctivitis and abdominal pain. Infectious and autoimmune causes were ruled out. No familial history was reported. Analysis of the tumour necrosis factor receptor superfamily 1A ( TNFRSF1A) gene identified a missense mutation (G36E) on exon 3. The absence of this variant in the patient’s parents and in controls identified it as a de novo disease-associated mutation. Clinical symptoms disappeared with administration of etanercept; however, levels of acute-phase reactants remained increased and could not be stabilised by the addition of colchicine. We believe that this patient gained some symptomatic relief with etanercept therapy, although not enough to completely avoid the risk of amyloidosis. Thus it is debatable whether etanercept alone or combined with other drugs, is the treatment of choice for patients with tumour necrosis factor receptor-associated Periodic syndrome. Conclusion:Since there is variability in treatment responses among different patients with tumour necrosis factor receptor-associated Periodic syndrome, we suggest that a systematic evaluation of acute-phase reactants, especially SAA-1, could be useful in maintaining or modifying a given therapeutic approach in these patients.
-
a severe autosomal dominant Periodic inflammatory disorder with renal aa amyloidosis and colchicine resistance associated to the mefv h478y variant in a spanish kindred an unusual familial mediterranean Fever phenotype or another mefv associated peri
American Journal of Medical Genetics Part A, 2004Co-Authors: Anna Aldea, Josep M Campistol, Juan I Arostegui, Josefa Rius, Montserrat Maso, Jordi Vives, Jordi YagueAbstract:Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of Fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease and around 30 mutations have been reported to date. Colchicine is the standard FMF treatment today, and prevents both attacks and amyloid deposition in 95% of patients. Here we describe a three-generation Spanish kindred with five family members affected by a severe Periodic inflammatory disorder associated with renal AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite FMF disease was made based on the Tel-Hashomer criteria set. Genetic analyses revealed that all subjects were heterozygous for the new H478Y MEFV variant, segregating with the disease. In addition, mutations in the TNFRSF1A and CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory Periodic syndromes, were ruled out. However, the dominant inheritance of the disease, the long Fever episodes with a predominant joint involvement, and the resistance to colchicine in these patients raise the question of whether the Periodic syndrome seen in this kindred is a true FMF disease with unusual manifestations or rather another MEFV-associated Periodic syndrome. We conclude that the new H478Y MEFV mutation is the dominant pathological variant causing the inflammatory Periodic syndrome in this kindred and that full-length analyses of the MEFV gene are needed to obtain an adequate diagnosis of patients with clinical suspicion of a Hereditary Periodic Fever syndrome, especially those from non-ancestral populations.
-
a severe autosomal dominant Periodic inflammatory disorder with renal aa amyloidosis and colchicine resistance associated to the mefv h478y variant in a spanish kindred an unusual familial mediterranean Fever phenotype or another mefv associated peri
American Journal of Medical Genetics Part A, 2004Co-Authors: Anna Aldea, Josep M Campistol, Juan I Arostegui, Josefa Rius, Montserrat Maso, Jordi Vives, Jordi YagueAbstract:Familial Mediterranean Fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of Fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease and around 30 mutations have been reported to date. Colchicine is the standard FMF treatment today, and prevents both attacks and amyloid deposition in 95% of patients. Here we describe a three-generation Spanish kindred with five family members affected by a severe Periodic inflammatory disorder associated with renal AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite FMF disease was made based on the Tel-Hashomer criteria set. Genetic analyses revealed that all subjects were heterozygous for the new H478Y MEFV variant, segregating with the disease. In addition, mutations in the TNFRSF1A and CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory Periodic syndromes, were ruled out. However, the dominant inheritance of the disease, the long Fever episodes with a predominant joint involvement, and the resistance to colchicine in these patients raise the question of whether the Periodic syndrome seen in this kindred is a true FMF disease with unusual manifestations or rather another MEFV-associated Periodic syndrome. We conclude that the new H478Y MEFV mutation is the dominant pathological variant causing the inflammatory Periodic syndrome in this kindred and that full-length analyses of the MEFV gene are needed to obtain an adequate diagnosis of patients with clinical suspicion of a Hereditary Periodic Fever syndrome, especially those from non-ancestral populations. © 2003 Wiley-Liss, Inc.
Simon A. - One of the best experts on this subject based on the ideXlab platform.
-
Long chain fatty acid (Lcfa) abnormalities in hyper Igd syndrome (Hids) and Familial Mediterranean Fever (Fmf): new insight into heritable Periodic Fevers
'Elsevier BV', 2013Co-Authors: Simon A., Drenth J.p.h., Matern D., Goetzman E.s., Hager E.j., Gibson K.m.Abstract:Item does not contain fulltextOBJECTIVE: To examine essential fatty acids (EFAs) in hyper-IgD syndrome (HIDS) and Familial Mediterranean Fever (FMF). METHODS: EFAs were determined in sera derived from an archival, cross-sectional group of HIDS/FMF patients, stratified for presence and absence of Fever. Control populations included healthy afebrile adults, and individuals with non-Periodic Fever (septic shock). EFAs were quantified using isotope dilution gas chromatography-mass spectrometry and data analyzed employing a Kruskal-Wallis non-parametric ANOVA with Dunn's post-hoc test. RESULTS: Sera samples derived from HIDS patients showed significantly decreased C20, C26, phytanic and pristanic acids during febrile crises that normalized in the afebrile state, and a significantly increased afebrile C22_4omega6 level that normalized with Fever. Samples derived from FMF patients revealed increased omega-oxidized LCFAs as compared to controls, and the trend was for these same species to be increased in comparison to febrile, but not afebrile, HIDS patients. Individuals with non-Periodic Fever demonstrated global decreases in C10-C24 fatty acids, both saturated and unsaturated, accompanied by an elevated triene/tetraene ratio. CONCLUSIONS: Our results suggest that different mechanisms are active in Hereditary Periodic Fever syndromes that appear unrelated to Fever, including depletion of very long chain fatty acids (VLCFAs) in febrile HIDS patients and increased omega-oxidized LCFAs in patients with FMF. These findings underscore new roles for EFAs in the potential production of inflammatory species in patients with Hereditary Periodic Fever
-
Long chain fatty acid (Lcfa) abnormalities in hyper Igd syndrome (Hids) and Familial Mediterranean Fever (Fmf): new insight into heritable Periodic Fevers
'Elsevier BV', 2013Co-Authors: Simon A., Drenth J.p.h., Matern D., Goetzman E.s., Hager E.j., Gibson K.m.Abstract:OBJECTIVE: To examine essential fatty acids (EFAs) in hyper-IgD syndrome (HIDS) and Familial Mediterranean Fever (FMF). METHODS: EFAs were determined in sera derived from an archival, cross-sectional group of HIDS/FMF patients, stratified for presence and absence of Fever. Control populations included healthy afebrile adults, and individuals with non-Periodic Fever (septic shock). EFAs were quantified using isotope dilution gas chromatography-mass spectrometry and data analyzed employing a Kruskal-Wallis non-parametric ANOVA with Dunn's post-hoc test. RESULTS: Sera samples derived from HIDS patients showed significantly decreased C20, C26, phytanic and pristanic acids during febrile crises that normalized in the afebrile state, and a significantly increased afebrile C22_4omega6 level that normalized with Fever. Samples derived from FMF patients revealed increased omega-oxidized LCFAs as compared to controls, and the trend was for these same species to be increased in comparison to febrile, but not afebrile, HIDS patients. Individuals with non-Periodic Fever demonstrated global decreases in C10-C24 fatty acids, both saturated and unsaturated, accompanied by an elevated triene/tetraene ratio. CONCLUSIONS: Our results suggest that different mechanisms are active in Hereditary Periodic Fever syndromes that appear unrelated to Fever, including depletion of very long chain fatty acids (VLCFAs) in febrile HIDS patients and increased omega-oxidized LCFAs in patients with FMF. These findings underscore new roles for EFAs in the potential production of inflammatory species in patients with Hereditary Periodic Fever
-
Dysregulation of innate immunity: Hereditary Periodic Fever syndromes.
'Wiley', 2009Co-Authors: Bodar E.j., Drenth J.p.h., Meer, J.w.m. Van Der, Simon A.Abstract:Contains fulltext : 80875.pdf (publisher's version ) (Closed access)The Hereditary Periodic Fever syndromes encompass a rare group of diseases that have lifelong recurrent episodes of inflammatory symptoms and an acute phase response in common. Clinical presentation can mimic that of lymphoproliferative disorders and patients often go undiagnosed for many years. These syndromes follow an autosomal inheritance pattern, and the major syndromes are linked to specific genes, most of which are involved in regulation of the innate immune response through pathways of apoptosis, nuclear factor kappaBeta activation and cytokine production. In others, the link between the protein involved and inflammation is less clear. The recurrent inflammation can lead to complications, such as renal impairment due to amyloidosis and vasculitis, visual impairment, hearing loss, and joint destruction, depending on the specific syndrome. In recent years, treatment options for these diseases have improved significantly. Early establishment of an accurate diagnosis and start of appropriate therapy improves prognosis in these patients
-
Lovastatin inhibits formation of AA amyloid.
'Society for Leukocyte Biology', 2008Co-Authors: Hilst, J.c.h. Van Der, Drenth J.p.h., Bodar E.j., Meer, J.w.m. Van Der, Kluve-beckerman B., Simon A.Abstract:Amyloid A (AA) amyloidosis is a severe complication of many chronic inflammatory disorders, including the Hereditary Periodic Fever syndromes. However, in one of these Periodic Fever syndromes, the hyper IgD and Periodic Fever syndrome, amyloidosis is rare despite vigorous, recurring inflammation. This Hereditary syndrome is caused by mutations in the gene coding for mevalonate kinase, an enzyme of the isoprenoid pathway. In this study, we used a cell culture system with human monocytes to show that inhibition of the isoprenoid pathway inhibits amyloidogenesis. Inhibition of the isoprenoid pathway by lovastatin resulted in a dose-dependent reduction of amyloid formed [53% at 10 microM (P=0.01)] compared with mononuclear cells that are exposed only to serum AA. The inhibitory effects of lovastatin are reversible by addition of farnesol but not geranylgeraniol. Farnesyl transferase inhibition also inhibited amyloidogenesis. These results implicate that the isoprenoid metabolism could be a potential target for prevention and treatment of AA amyloidosis
-
Lovastatin inhibits formation of AA amyloid.
'Society for Leukocyte Biology', 2008Co-Authors: Hilst, J.c.h. Van Der, Drenth J.p.h., Bodar E.j., Meer, J.w.m. Van Der, Kluve-beckerman B., Simon A.Abstract:Item does not contain fulltextAmyloid A (AA) amyloidosis is a severe complication of many chronic inflammatory disorders, including the Hereditary Periodic Fever syndromes. However, in one of these Periodic Fever syndromes, the hyper IgD and Periodic Fever syndrome, amyloidosis is rare despite vigorous, recurring inflammation. This Hereditary syndrome is caused by mutations in the gene coding for mevalonate kinase, an enzyme of the isoprenoid pathway. In this study, we used a cell culture system with human monocytes to show that inhibition of the isoprenoid pathway inhibits amyloidogenesis. Inhibition of the isoprenoid pathway by lovastatin resulted in a dose-dependent reduction of amyloid formed [53% at 10 microM (P=0.01)] compared with mononuclear cells that are exposed only to serum AA. The inhibitory effects of lovastatin are reversible by addition of farnesol but not geranylgeraniol. Farnesyl transferase inhibition also inhibited amyloidogenesis. These results implicate that the isoprenoid metabolism could be a potential target for prevention and treatment of AA amyloidosis
Luca Cantarini - One of the best experts on this subject based on the ideXlab platform.
-
an international delphi survey for the definition of new classification criteria for familial mediterranean Fever mevalonate kinase deficiency tnf receptor associated Periodic Fever syndromes and cryopyrin associated Periodic syndrome
The Journal of Rheumatology, 2019Co-Authors: Silvia Federici, Raphaela Goldbachmansky, Eldad Benchetrit, Hal M Hoffman, Luca Cantarini, Ahmet Gül, Isabelle Konepaut, Federica Vanoni, Jasmin B KuemmerledeschnerAbstract:Objective. Provisional evidence-based classification criteria for Hereditary Periodic Fever (HPF) have been recently developed. However, no consensus on how to combine clinical criteria, laboratory tests, and results of molecular analysis has been reached. The objective of this study is to understand which variables physicians consider important for the classification of patients with HPF. Methods. Two Delphi surveys were sent to health professionals in the field of autoinflammation. In the first open survey, 124 researchers could list all the variables they consider useful for the diagnosis of each monogenic Periodic Fever. The variables could be of any type and each researcher could complete the survey for 1 or more diseases. In the second survey, 162 researchers were asked to select, from a list of items coming from the first survey, the 10 top variables and to rank them by assigning a score from 10 to 1. Results. The response rates to the Delphi surveys were 85% for the first session and 87% for the second. The variables selected for each disease (corresponding to the third quartile, considering the total score obtained by the variables after the second Delphi survey) were 21 for mevalonate kinase deficiency, 22 for cryopyrinopathies, 18 for familial Mediterranean Fever, and 20 for tumor necrosis factor receptor–associated Periodic Fever syndrome. A positive genetic test reached the top rank in all the HPF. Conclusion. Our process led to the identification of those features considered the most important as candidate variables to be included in a new set of evidence-based classification criteria for HPF.
-
A Comprehensive Overview of the Hereditary Periodic Fever Syndromes
Clinical Reviews in Allergy & Immunology, 2018Co-Authors: Donato Rigante, Bruno Frediani, Luca CantariniAbstract:Innate immunity is a critical partner in the regulation of inflammation and some mutations in genes implied in innate immunity pathways can cause genetic disorders characterized by seemingly unprovoked self-limited inflammatory attacks. These rare conditions are collectively named “Hereditary Periodic Fever syndromes” (HPFS), and protean pathogenetic mechanisms combined with several clinical phenotypes characterize at least four distinct conditions: (1) familial Mediterranean Fever, which is the prototype and the most widely recognized among HPFS, inherited as an autosomal recessive disorder showing recurrent dysregulated inflammatory processes, caused by an abnormal interaction between cytoskeleton and inflammasome, a key-signaling platform that releases interleukin-1β (IL-1β); (2) the group of cryopyrin-associated Periodic syndrome, which upsets directly the production of IL-1β, with a dominant pattern of inheritance; (3) tumor necrosis factor receptor-associated Periodic syndrome, which is an autosomal dominant disorder subverting the functions and traffic of a cell membrane protein; and (4) mevalonate kinase deficiency, which is an autosomal recessive metabolic disorder halting the biosynthesis of cholesterol. MEFV , NLRP3 , TNFRSF1A , and MVK are respectively the four causing genes of these conditions, all resulting in excessive IL-1β signaling, though the encoded proteins act at different levels in cytoskeletal filament organization, apoptosis, and activation of the IL-1β-structured inflammasome. The differential diagnosis of HPFS can be challenging, as there are no universally accepted diagnostic algorithms, and near half of patients may have a specific disease without any genetic pathogenetic variant identified. Herein, we outline the most relevant aspects of HPFS at the crossroads between clinical medicine and immunology and all the most recent advances in their treatment, as the increasing use of IL-1 antagonists has achieved unexpected clinical results in a large number of patients.
-
Role of Autoimmunity and Autoinflammation in the Pathogenesis of Idiopathic Recurrent Pericarditis
Clinical Reviews in Allergy & Immunology, 2013Co-Authors: Luca Cantarini, Orso Maria Lucherini, Massimo Imazio, Maria Giuseppina Brizi, Antonio Brucato, Rolando Cimaz, Mauro GaleazziAbstract: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.
-
The diagnostic evaluation of patients with potential adult-onset autoinflammatory disorders : our experience and review of the literature
'Elsevier BV', 2012Co-Authors: I. Muscari, Luca Cantarini, Bruno Frediani, Om Lucherini, F. Iacoponi, G. Simonini, M.g. Brizi, A. Vitale, R. Cimaz, Mauro GaleazziAbstract: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
Tadej Avcin - One of the best experts on this subject based on the ideXlab platform.
-
PIK3AP1 and SPON2 Genes Are Differentially Methylated in Patients With Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) Syndrome
Frontiers in Immunology, 2020Co-Authors: E. Lovšin, Daša Perko, Maruša Debeljak, Nataša Toplak, Jernej Kovač, Tine Tesovnik, Tomaž Rozmarič, Tadej AvcinAbstract:Periodic Fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is the most common autoinflammatory disease in children and is often grouped together with Hereditary Periodic Fever syndromes, although its cause and Hereditary nature remain unexplained. We investigated whether differential DNA methylation was present in DNA from peripheral blood mononuclear cells (PBMC) in patients with PFAPA vs. healthy controls. A whole-epigenome analysis (MeDIP and MBD) was performed using pooled DNA libraries enriched for methylated genomic regions and identified candidate genes, two of which were further evaluated with methylation-specific restriction enzymes coupled with qPCR (MSRE-qPCR). The analysis showed that the PIK3AP1 and SPON2 gene regions are differentially methylated in patients with PFAPA. MSRE-qPCR proved to be a quick, reliable, and cost-effective method of confirming results from MeDIP and MBD. Our findings indicate that a B-cell adapter protein (PIK3AP1), as the PI3K binding inhibitor of inflammation, and spondin-2 (SPON2), as a pattern recognition molecule and integrin ligand, could play a role in the etiology of PFAPA. Their role and the impact of changed DNA methylation in PFAPA etiology and autoinflammation need further investigation.
-
THU0019 INTRON REGIONS OF PIK3AP1 (BCAP) AND SPON2 (SPONDIN-2) GENES ARE DIFFERENTIALLY METHYLATED IN PATIENTS WITH Periodic Fever, APHTHOUS STOMATITIS, PHARYNGITIS AND ADENITIS (PFAPA) SYNDROME
Annals of the Rheumatic Diseases, 2020Co-Authors: E. Lovšin, Daša Perko, Maruša Debeljak, Nataša Toplak, Jernej Kovač, Tine Tesovnik, Tomaž Rozmarič, Tadej AvcinAbstract:Background: Periodic Fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome is the most common autoinflammatory disease in children, often grouped together with Hereditary Periodic Fever syndromes, although its cause and Hereditary nature remain unexplained. Objectives: We investigated whether a differential DNA methylation was present in DNA from peripheral blood mononuclear cells (PBMC) in patients with PFAPA versus a group of healthy young individuals. Methods: A whole epigenome analysis (MeDIP and MBD) was performed using pooled DNA libraries enriched for methylated genomic regions. Of identified candidate genes, two with most significantly different methylation leves were further evaluated with methylation specific restriction enzymes coupled with qPCR (MSRE-qPCR). Results: The analysis showed that PIK3AP1 and SPON2 intronic gene regions are differentially methylated in patients with PFAPA. MSRE-qPCR proved as a quick, reliable and cost-effective method to confirm results from MeDIP and MBD. Conclusion: Our findings indicate that B cell adapter protein (BCAP) as PI3K binding inhibitor of inflammation and spondin-2 (SPON2) as a pattern recognition molecule and integrin ligand could play a role in etiology of PFAPA. Their role and impact of changed DNA methylation in PFAPA etiology and autoinflammation need further investigation. References: [1]Wekell P. Periodic Fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome – PFAPA syndrome. Press Medicale [Internet]. 2019;48(1):e77–87. Available from: https://doi.org/10.1016/j.lpm.2018.08.016 [2]K. Theodoropoulou, F. Vanoni, and M. Hofer, “Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: a Review of the Pathogenesis,” Curr. Rheumatol. Rep., vol. 18:18, 2016. [3]Carpentier SJ, Ni M, Duggan JM, James RG, Cookson BT, Hamerman JA. The signaling adaptor BCAP inhibits NLRP3 and NLRC4 inflammasome activation in macrophages through interactions with Flightless-1. Sci Signal. 2019;12(581). [4]He YW, Li H, Zhang J, Hsu CL, Lin E, Zhang N, et al. The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens. Nat Immunol. 2004;5(1):88–97. Disclosure of Interests: None declared
Kristi L Williams - One of the best experts on this subject based on the ideXlab platform.
-
blimp 1 prdm1 mediates transcriptional suppression of the nlr gene nlrp12 monarch 1
Journal of Immunology, 2009Co-Authors: Christopher A Lord, David Savitsky, Raquel Sitcheran, Kathryn Calame, Jo Rae Wright, Kristi L WilliamsAbstract:NLR (nucleotide-binding domain, leucine-rich repeat) proteins are intracellular regulators of host defense and immunity. One NLR gene, NLRP12 (NLR family, pyrin domain containing 12)/ Monarch-1 , has emerged as an important inhibitor of inflammatory gene expression in human myeloid cells. This is supported by genetic analysis linking the loss of a functional NLRP12 protein to Hereditary Periodic Fever. NLRP12 transcription is diminished by specific TLR stimulation and myeloid cell maturation, consistent with its role as a negative regulator of inflammation. The NLRP12 promoter contains a novel Blimp-1 (B lymphocyte-induced maturation protein-1)/PRDM1 (PR domain-containing 1, with ZNF domain) binding site, and Blimp-1 reduces NLRP12 promoter activity, expression, and histone 3 acetylation. Blimp-1 associates with the endogenous NLRP12 promoter in a TLR-inducible manner and mediates the down-regulation of NLRP12 expression by TLR agonists. As expected, the expression of NLRP12 and Blimp-1 is inversely correlated. Analysis of Blimp-1 −/− murine myeloid cells provides physiologic evidence that Blimp-1 reduces NLRP12 gene expression during cell differentiation. This demonstrates a novel role for Blimp-1 in the regulation of an NLR gene.