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1.
An Acad Bras Cienc ; 93(suppl 4): e20210618, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34730627

RESUMO

Fibromyalgia (FM) is a chronic pain syndrome that affects the central nervous system and generates disability, which is characterized by generalized pain, fatigue, and functional decline. In this review, we aimed to identify the polymorphisms related to the pathophysiology of FM and the clinical characteristics generated by genetic influence. Only original studies with genes related to FM were considered, totaling 27 articles. The genes found were: MTHFR, RGS4, MYT1L, TACR1, SCN9A, DRD3, ADRB2, IL-4, HLA-DRB1, EDN1, CNR1, TAAR1, OPRM1, ADRA1A, ADRB3, BDNF, GRIA4, HTR3A, HTR3B, HTR2A, SERPINA 1 or A1AT, NRXN3, GCH1, MEFV, TRPV3, SLC6A4, ACE I/D, TSPO, COMT, and MAOA. Several genes related to different pain syndromes and altered pain thresholds have been identified and some polymorphisms were related to susceptibility to FM. It was observed that 73.33% of the genes related to FM were also associated with some psychological disorders, such as anxiety, depression, schizophrenia, and obsessive and compulsive disorder, and 40.00% with pain sensitivity and/or migraine, besides other disorders associated (drug addiction, autoimmune disorders, circulatory problems, and metabolic alterations). This review demonstrated an association of FM and genetic polymorphisms that can expand our knowledge about the pathophysiology of this disease.


Assuntos
Fibromialgia , Homocistinúria , Fibromialgia/genética , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2) , Canal de Sódio Disparado por Voltagem NAV1.7 , Dor , Polimorfismo Genético/genética , Pirina , Receptores Adrenérgicos beta 3 , Receptores de GABA , Proteínas da Membrana Plasmática de Transporte de Serotonina
2.
Nature ; 597(7876): 415-419, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34471287

RESUMO

Inflammasomes are important sentinels of innate immune defence, sensing pathogens and inducing cell death in infected cells1. There are several inflammasome sensors that each detect and respond to a specific pathogen- or damage-associated molecular pattern (PAMP or DAMP, respectively)1. During infection, live pathogens can induce the release of multiple PAMPs and DAMPs, which can simultaneously engage multiple inflammasome sensors2-5. Here we found that AIM2 regulates the innate immune sensors pyrin and ZBP1 to drive inflammatory signalling and a form of inflammatory cell death known as PANoptosis, and provide host protection during infections with herpes simplex virus 1 and Francisella novicida. We also observed that AIM2, pyrin and ZBP1 were members of a large multi-protein complex along with ASC, caspase-1, caspase-8, RIPK3, RIPK1 and FADD, that drove inflammatory cell death (PANoptosis). Collectively, our findings define a previously unknown regulatory and molecular interaction between AIM2, pyrin and ZBP1 that drives assembly of an AIM2-mediated multi-protein complex that we term the AIM2 PANoptosome and comprising multiple inflammasome sensors and cell death regulators. These results advance the understanding of the functions of these molecules in innate immunity and inflammatory cell death, suggesting new therapeutic targets for AIM2-, ZBP1- and pyrin-mediated diseases.


Assuntos
Apoptose/imunologia , Proteínas de Ligação a DNA/metabolismo , Necroptose/imunologia , Pirina/metabolismo , Piroptose/imunologia , Proteínas de Ligação a RNA/metabolismo , Animais , Caspase 1/metabolismo , Células Cultivadas , Citocinas/metabolismo , Feminino , Francisella , Herpesvirus Humano 1 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células THP-1
3.
Clin J Gastroenterol ; 14(6): 1661-1666, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34427863

RESUMO

An 86-year-old woman was admitted to our hospital with anemia. She had never experienced symptoms of serositis. Colonoscopy revealed colitis with erosions and a friable mucosa. First, she was diagnosed with unclassified inflammatory bowel disease (IBD-U). We suspected familial Mediterranean fever as a differential diagnosis of IBD-U, and MEFV gene analysis showed heterozygosity for Exon2 R202Q. The patient was treated with colchicine 0.5 mg. After 4 months, a follow-up colonoscopy showed remarkable improvement of the mucosal inflammation throughout the entire colon. MEFV gene-associated enterocolitis responding to colchicine may be observed in patients with IBD-U and elucidating the role of MEFV gene mutations in intestinal inflammation is a future challenge.


Assuntos
Enterocolite , Febre Familiar do Mediterrâneo , Pirina , Idoso de 80 Anos ou mais , Colchicina/uso terapêutico , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Feminino , Humanos , Japão , Mutação , Pirina/genética
4.
Curr Opin Rheumatol ; 33(5): 398-402, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397603

RESUMO

PURPOSE OF REVIEW: Familial Mediterranean fever (FMF) is the prototypic autoinflammatory disease. Although the gene associated with the disease was identified 24 years ago, we still have to learn about the pathogenesis of its inflammation and the variation in the phenotype. In this review, we discuss some recent findings in FMF, such as changes in our understanding of the genetics, aims to define new criteria, and factors contributing to the disease presentation. RECENT FINDINGS: We finally have learned why a mutation causing this disease was selected in ancient times; MEFV gene mutations confer resistance to the microbe of plague. A group of experts have outlined recommendations for the analysis of the genetics of FMF. These recommendations complement the new classification criteria, which includes genetic results. In the past year, a number of studies have addressed the contributing factors to the inflammation caused by the mutations in pyrin; this has included epigenetic studies as well. Finally, we have long-term data for the use of anti-IL1 treatment in colchicine-resistant patients. SUMMARY: We now have recommendations for assessing genetic analysis of the MEFV gene and how to reliably classify a patient as FMF. We await further data to understand the contributing genetic and environmental factors that affect the inflammation and final phenotype in FMF and the extent of the disease presentation.


Assuntos
Febre Familiar do Mediterrâneo , Colchicina , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/genética , Humanos , Mutação , Fenótipo , Pirina/genética
5.
J Trop Pediatr ; 67(3)2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34363075

RESUMO

BACKGROUND: Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by abdominal and chest pain and recurrent fever due to inflammation in the serosal membranes such as peritoneum, pleura and synovia. In FMF, recurrent inflammatory cytokine production may lead to cirrhosis. The aim of this study was to determine the prevalence of FMF in children with cryptogenic cirrhosis and it was found to be high, to add FMF among the etiological causes of cirrhosis. MATERIALS AND METHODS: This prospective cohort study conducted at the Hospital of Inönü University, Malatya, Turkey. In this study, 44 patients diagnosed with cryptogenic cirrhosis by biopsy, in the Pediatric Gastroenterology, Hepatology and Nutrition Clinic, were included, after the other reasons that may cause chronic liver disease were excluded. MEVF gene analysis was performed for all patients with cryptogenic cirrhosis. RESULTS: FMF genetic mutation was detected in 9 (20%) of 44 patients. M694V mutation was detected in one patient (2.27%) and E148Q homozygous mutation was detected in one patient (2.27%). Various other heterozygous mutations were detected in seven other patients. Homozygous and heterozygous R202Q mutations were detected in one patient. CONCLUSION: We suggest that FMF plays a role in the etiologic differential diagnosis of cryptogenic cirrhosis.


Assuntos
Febre Familiar do Mediterrâneo , Criança , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Humanos , Cirrose Hepática/epidemiologia , Prevalência , Estudos Prospectivos , Pirina/genética
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(8): 719-722, 2021 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-34365609

RESUMO

OBJECTIVE: To analyze a pathogenic variant of MEFV gene in a family with autosomal dominant-familial Mediterranean fever (AD-FMF). METHODS: A 5-year-old boy presented with recurrent aseptic meningitis and his major symptoms included recurrent fever with headache and vomiting. His family members including his mother, sister and brother also had recurrent fever. A genetic disease was considered. DNAs were extracted from patient and all his family members' blood samples. Whole exome sequencing was performed to identify putative pathogenic variants that can explain this family's condition and Sanger sequencing was conducted. The impact of detected variants were predicted and validated by bioinformatics. RESULTS: A missense variant c.2229C>G (p.Phe743Leu) in MEFV gene was identified in the proband and his family members including his mother, sister and brother. This variant had not been reported in China previously, but the locus of it had already been reported in Arabic patient with AD-FMF (PS1). This variant was absent in major allele frequency databases (PM2) and had been predicted to be pathogenic based on Mutationtaster, PROVEAN and PolyPhen-2. In addition, the change of amino acid, locating in 743 locus of pyrin protein, encoding by MEFV gene, was found to cause SPRY_PRY_TRIM20 and SPRY_superfamily domain destroyed and finally influenced the fuction of pyrin protein. On the other hand, using UCSF chimera software, we find the variant c.2229C>G (p.Phe743Leu) can induce serious influence to the spatial structure of pyrin protein and loss of protein fuction (PP3). According to the ACMG variant classification guideline, the variant c.2229C>G (p.Phe743Leu) in MEFV gene was classified as likely pathogenic (PS1+PM2+PP3). CONCLUSION: The condition of this AD-FMF family may be attributed to the missense variant c.2229C>G (p.Phe743Leu) in MEFV gene. The recurrent aseptic meningitis was a very rare manifestation in AD-FMF patients and had not been reported in China previously. The clinical and genetic findings of the present study are helpful for the further understanding of AD-FMF.


Assuntos
Febre Familiar do Mediterrâneo , Pré-Escolar , Febre Familiar do Mediterrâneo/genética , Frequência do Gene , Testes Genéticos , Humanos , Masculino , Mutação , Pirina/genética , Sequenciamento Completo do Exoma
7.
Clin Exp Rheumatol ; 39 Suppl 132(5): 18-21, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34251301

RESUMO

OBJECTIVES: Familial Mediterranean fever (FMF) is an autosomal-recessive, inflammatory disorder characterised by short, recurrent attacks of fever, accompanied by pain in the abdomen, chest, or joints and complications of amyloidosis. Recently, we observed a significant association between the serum amyloid A1 (SAA1) ß/ß genotype and a delayed disease onset in 386 M694V homozygous FMF patients. This follow-up study was conducted to additionally analyse MEFV genotypes other than M694V/M694V for a possible influence of the SAA1 genotype on the age of disease onset. METHODS: A total of 700 Armenian patients diagnosed with FMF based on the Tel-Hashomer criteria and carrying two MEFV mutant alleles were included in this study. Patients were divided into three MEFV genotypic subgroups: M694V homozygotes (M694V/M694V), M694V compound heterozygotes (M694V/Other), and patients with genotypes excluding M694V (Other/Other). MEFV and SAA1 analyses were performed by a commercial reverse-hybridisation assay, and resulting genotypes were matched against the demographic and clinical characteristics of the patients. RESULTS: Within the subgroup of M694/M694 homozygotes, SAA1 genotype ß/ß could be identified in 115 (34.43%) and 32 (61.54%) patients with an age of onset <20 and ≥20 years, respectively(p<0.001). However, no such relationship could be observed for MEFV genotypic subgroups M694V/Other (p=0.465) and Other/Other (p=0.697). CONCLUSIONS: Our data suggest, that the influence of SAA1 genotypic variation on the age of disease onset restricts to FMF patients homozygous for MEFV mutation M694V.


Assuntos
Febre Familiar do Mediterrâneo , Proteína Amiloide A Sérica/genética , Adulto , Idade de Início , Armênia , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/genética , Seguimentos , Genótipo , Homozigoto , Humanos , Mutação , Pirina/genética , Adulto Jovem
8.
Clin Exp Rheumatol ; 39 Suppl 132(5): 102-108, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34251310

RESUMO

OBJECTIVES: The severity of familial Mediterranean fever (FMF) may vary in different areas, suggesting a role for environmental factors. We analysed the composition of gut microbiota among children with FMF and healthy controls from Turkey and the USA and determined its effect on disease severity. METHODS: Children with FMF with pathogenic MEFV mutations and healthy controls from Turkey and the USA were enrolled. FMF disease activity was evaluated with the Autoinflammatory Disease Activity Index (AIDAI). Gut bacterial diversity was assessed by sequencing 16S rRNA gene libraries. RESULTS: We included 36 children from Turkey (28 patients with FMF, 8 healthy controls), and 21 patients and 6 controls from the USA. In the Turkish group, 28.6% of patients had severe disease, while 13.3% of US group patients had severe disease. As expected, we observed substantial differences between the gut microbiota of children from the two geographic regions, with Turkish patients and controls exhibiting higher relative abundances of Bacteriodia, while US patients and controls exhibited higher relative abundances of Clostridia. Alpha- and betadiversity did not differ significantly between FMF patients and controls, and neither was predictive of disease severity within each geographic region. We observed differences between FMF patients and controls in the relative abundance of some bacterial taxa at the amplicon sequence variant (ASV) level, but these differences received mixed statistical support. CONCLUSIONS: Among an international cohort of children with FMF, we did not find a strong effect of gut microbiota composition on disease severity. Other environmental or epigenetic factors may be operative.


Assuntos
Febre Familiar do Mediterrâneo , Microbioma Gastrointestinal , Criança , Estudos de Coortes , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/genética , Humanos , Mutação , Pirina/genética , RNA Ribossômico 16S , Índice de Gravidade de Doença , Turquia
9.
FASEB J ; 35(8): e21757, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34233045

RESUMO

Pyroptosis and intrinsic apoptosis are two forms of regulated cell death driven by active caspases where plasma membrane permeabilization is induced by gasdermin pores. Caspase-1 induces gasdermin D pore formation during pyroptosis, whereas caspase-3 promotes gasdermin E pore formation during apoptosis. These two types of cell death are accompanied by mitochondrial outer membrane permeabilization due to BAK/BAX pore formation in the external membrane of mitochondria, and to some extent, this complex also affects the inner mitochondrial membrane facilitating mitochondrial DNA relocalization from the matrix to the cytosol. However, the detailed mechanism responsible for this process has not been investigated. Herein, we reported that gasdermin processing is required to induce mitochondrial DNA release from cells during pyroptosis and apoptosis. Gasdermin targeted at the plasma membrane promotes a fast mitochondrial collapse along with the initial accumulation of mitochondrial DNA in the cytosol and then facilitates the DNA's release from the cell when the plasma membrane ruptures. These findings demonstrate that gasdermin action has a critical effect on the plasma membrane and facilitates the release of mitochondrial DNA as a damage-associated molecular pattern.


Assuntos
Apoptose/fisiologia , DNA Mitocondrial/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Proteínas de Ligação a Fosfato/fisiologia , Piroptose/fisiologia , Animais , Caspases/metabolismo , Membrana Celular/metabolismo , Células HEK293 , Humanos , Técnicas In Vitro , Inflamassomos/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Peptídeos e Proteínas de Sinalização Intracelular/genética , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas de Ligação a Fosfato/deficiência , Proteínas de Ligação a Fosfato/genética , Pirina/metabolismo , Receptores de Estrogênio/fisiologia
11.
J Dermatol ; 48(9): 1453-1456, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34142384

RESUMO

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent febrile attacks and serositis. The diagnosis of FMF has been based on clinical criteria, including frequent symptoms and good response to the treatment with colchicine. Some patients with FMF show skin or muscle manifestations, which may be confused with other cutaneous or muscle disorders. Here we report a female in her 40s with periodic fever, migratory myalgia, dermatomyositis-like dermatitis, arthralgia, pharyngalgia, and lymphadenopathy. The initial clinical differential diagnosis included dermatomyositis, malignant lymphoma, and adult-onset Still's disease. However, the following examinations could not explain her pathological condition with such diseases. In particular, findings from muscle and fascial biopsy demonstrated severe inflammatory cell infiltrate in the fascia, suggesting fasciitis as a possible cause of migratory myalgia. We examined the possibility of autoinflammatory diseases by genetic testing. Accordingly, she was found to have novel compound heterozygous mutations (L110P, E148Q, and P369S) in the MEFV gene. Given her genetic mutations and favorable response to colchicine, she was finally diagnosed as a variant of FMF with myalgia and previously unprecedented skin eruptions.


Assuntos
Dermatomiosite , Febre Familiar do Mediterrâneo , Fasciite , Pirina , Adulto , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Dermatomiosite/genética , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/genética , Fasciite/diagnóstico , Fasciite/tratamento farmacológico , Fasciite/genética , Feminino , Humanos , Mutação , Pirina/genética
13.
Clin Rheumatol ; 40(11): 4437-4444, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34014414

RESUMO

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disorder with an uncertain origin. PFAPA manifestations occur in the form of regular attacks accompanied by a rise in inflammatory markers. Regarding the family clustering of PFAPA and its similarities with other autoinflammatory disorders such as familial Mediterranean fever, a genetic basis is suggested for the disease. Studies have conducted genome analysis in order to find possible gene variants in PFAPA. Associations with variations in several genes such as MEFV, NLRP, TNFRSF1A, CARD15/NOD2, and MVK have been suggested and analyzed. Inflammasomes, intracellular proteins that are members of innate immunity and activate interleukin-1b (IL-1b) and IL-18, are proposed to be involved in PFAPA pathogenesis. The investigations show that a single gene cannot be found in association with PFAPA, and that it might have a multifactorial or polygenic basis, in which an environmental trigger can provoke inflammasome activation and activate PFAPA flares.


Assuntos
Linfadenite , Faringite , Estomatite Aftosa , Febre/genética , Patrimônio Genético , Humanos , Linfadenite/genética , Faringite/genética , Pirina/genética , Estomatite Aftosa/genética
14.
Kobe J Med Sci ; 66(5): E159-E165, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34001682

RESUMO

Familial Mediterranean Fever (FMF) is an autosomal recessive disorder, characterized by recurrent attacks of fever, serositis and articular pain. Mutations in the MEFV gene causes inflammation that may trigger cognitive impairment in FMF patients. The objectives were to identify the effect of anti-inflammatory diet containing curcumin, flaxseed and vitamin D supplementation on the clinical presentation and cognitive functions of FMF patients. The study included 73 FMF patients, that followed in addition to their regular colchicine doses an anti-inflammatory diet (rich in fresh vegetables and fruits, low in saturated and unsaturated fats and carbohydrates, low in food additives, sugar, fast foods and processed foods). In addition, to dietary supplementation with vitamin D, curcumin and flax seeds. Results: Statistically significant improvement was observed regarding clinical presentation, cognitive functions, CRP and subjective wellbeing. Conclusion: Our study highlights the importance of anti-inflammatory diet in the amelioration of the clinical presentation, cognitive functions and general wellbeing of FMF patients. We recommend that our findings would be confirmed by a randomized controlled trial.


Assuntos
Cognição , Curcumina/administração & dosagem , Febre Familiar do Mediterrâneo/dietoterapia , Febre Familiar do Mediterrâneo/genética , Linho , Vitamina D/uso terapêutico , Adolescente , Criança , Colchicina/uso terapêutico , Curcumina/uso terapêutico , Suplementos Nutricionais , Febre Familiar do Mediterrâneo/tratamento farmacológico , Feminino , Amplificação de Genes , Supressores da Gota/uso terapêutico , Humanos , Masculino , Reação em Cadeia da Polimerase , Pirina , Resultado do Tratamento , Moduladores de Tubulina/uso terapêutico , Vitamina D/administração & dosagem , Adulto Jovem
15.
BMJ Case Rep ; 14(5)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011672

RESUMO

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by a pyrin dysfunction, leading to uncontrolled interleukin-1 production that triggers the attacks. Here we report a case of a 36-year-old female patient repeatedly admitted to the cardiology ward with recurrent episodes of pericarditis, with intervals of 1 and 2 months between the episodes. During the attacks, chest pain and fever were the only symptoms. Following the administration of steroids and non-steroidal anti-inflammatory drugs, the patient became afebrile. She also had lymphoma and thyroid carcinoma in anamnesis essential for differential diagnosis. Laboratory tests for infection and autoimmune disease were all negative, and the positron emission tomography-CT scan did not reveal lymphoma relapse. Genetic testing revealed a mutation in the MEFV gene. It is very rare for pericarditis to be the first and only manifestation of FMF.


Assuntos
Febre Familiar do Mediterrâneo , Pericardite , Adulto , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/genética , Feminino , Febre , Humanos , Mutação , Recidiva Local de Neoplasia , Pericardite/etiologia , Pirina/genética
16.
Lupus ; 30(7): 1094-1099, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33794705

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease characterized by antibody production against a myriad of autoantigens. Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder, triggered by FMF-associated point genes mutations. It has been hypothesized that the two conditions rarely coexist. AIM: The aim of this study was to examine the proportions of FMF among SLE patients compared with the general population without SLE. We hypothesized that the proportion of FMF among SLE patients might be higher than the general population. METHODS: To conduct this cross-sectional study, data of adult patients with a physician diagnosis of SLE were retrieved from Clalit Health Services database, the largest Health Maintenance Organization in Israel, serving 4,400,000 members. Chi-square and T-test was used for univariate analysis. RESULTS: The study population included 4,886 SLE patients and 24,430 age and sex matched controls. Within the SLE group we detected a significantly higher proportion of FMF patients compared with non-SLE controls (0.68% and 0.21% respectively; p < 0.001). CONCLUSIONS: Our study indicated that FMF is more prevalent in an Israeli population of SLE patients.


Assuntos
Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/genética , Doenças Hereditárias Autoinflamatórias/genética , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Febre Familiar do Mediterrâneo/epidemiologia , Feminino , Humanos , Imunidade Inata/imunologia , Interleucina-1beta/metabolismo , Israel/epidemiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Proteínas NLR/genética , Prevalência , Pirina/genética
17.
Nephrol Ther ; 17S: S119-S125, 2021 Apr.
Artigo em Francês | MEDLINE | ID: mdl-33910693

RESUMO

Familial Mediterranean fever is the most frequent autoinflammatory disease with autosomal recessive transmission. Most patients carry mutations in the MEFV gene encoding the protein marenostrin/pyrin. It is characterised by short ant recurrent attacks of fever and serositis with abdominal or thoracic pain, usually lasting less than 3 days, raised inflammatory biologic markers in an individual of Mediterranean origin. Colchicine has been shown to be effective in prevention of inflammatory attacks and development of amyloidosis which is responsible of nephrotic syndrome and chronic renal failure. Better knowledge in pathogenic mechanisms permitted identification of interleukin-1 beta (Il-1 ß) as the main cytokine target. Anti-IL-1 therapy must be considered as a second line treatment in case of persistent inflammation or colchicine intolerance.


Assuntos
Amiloidose , Febre Familiar do Mediterrâneo , Colchicina/uso terapêutico , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Febre Familiar do Mediterrâneo/genética , Humanos , Mutação , Pirina/genética
18.
Clin Rheumatol ; 40(10): 4199-4206, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33813620

RESUMO

OBJECTIVES: This study aimed to evaluate the risk for atherosclerosis by using echocardiographic arterial stiffness (AS) parameters and serum endocan levels, as a biomarker of endothelial dysfunction (ED) in children with FMF. METHODS: Seventy-nine children with FMF (12-18 years) and 41 healthy children were included, and clinical features (age at the first attack, age at the time of diagnosis, diagnosis delay time, colchicine dose, biological agent usage, MEFV mutations, and symptoms of attacks) of patients were noted. Arterial stiffness parameters were calculated by using echocardiographic aortic measurements with blood pressure monitoring. Hemogram parameters, acute phase reactants, blood glucose and lipid levels of 12 hours of fasting, and serum endocan levels were evaluated for all participants. RESULTS: There were no statistically significance regarding demographic features, acute phase reactants, and hemogram parameters. Blood glucose and lipid levels were similar, except for HDL (lower in FMF group, p=0.029). Serum endocan levels did not differ in two groups (p=0.906). Only stiffness of descending aorta was lower in FMF group (p=0.028), and the other AS parameters were similar between two groups (p>0.05 for each parameters). CONCLUSION: Good disease control could be preventive for atherosclerosis in children with FMF. On the other hand, screening for cardiovascular diseases is essential, particularly for uncontrolled cases. Distribution of MEFV gene mutations KEY POINTS: • Exaggerated inflammation is the prominent feature of FMF attacks; moreover, it is shown that subclinical inflammation might also continue in attack-free periods. • Chronic inflammation contributes to atherosclerotic process in almost all stages by activating endothelial cells, producing reactive oxygen species, and accelerating foam cell and atherosclerotic plaque formations. • However, the results of this study showed that there was no difference in terms of atherosclerotic markers such as serum endocan levels and arterial stiffness parameters between pediatric FMF patients and healthy peers. • Good disease control in pediatric FMF patients may prevent early atherosclerotic changes during childhood, which then may lead a probable decreased risk of subsequent CVD in adulthood.


Assuntos
Aterosclerose , Febre Familiar do Mediterrâneo , Rigidez Vascular , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Colchicina , Células Endoteliais , Febre Familiar do Mediterrâneo/complicações , Humanos , Pirina
19.
PLoS Pathog ; 17(4): e1009504, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33914853

RESUMO

Pathogens have evolved smart strategies to invade hosts and hijack their immune responses. One such strategy is the targeting of the host RhoGTPases by toxins or virulence factors to hijack the cytoskeleton dynamic and immune processes. In response to this microbial attack, the host has evolved an elegant strategy to monitor the function of virulence factors and toxins by sensing the abnormal activity of RhoGTPases. This innate immune strategy of sensing bacterial effector targeting RhoGTPase appears to be a bona fide example of effector-triggered immunity (ETI). Here, we review recently discovered mechanisms by which the host can sense the activity of these toxins through NOD and NOD-like receptors (NLRs).


Assuntos
Bactérias/imunologia , Inflamassomos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR/metabolismo , Transdução de Sinais , Fatores de Virulência/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Toxinas Bacterianas/metabolismo , Citoesqueleto/imunologia , Imunidade Inata , Pirina/metabolismo
20.
J Pak Med Assoc ; 71(2(A)): 479-483, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33819232

RESUMO

OBJECTIVE: To determine the cumulative effects of Mediterranean fever gene polymorphisms and mutations in patients with inflammatory bowel diseases. METHODS: The case-control study was conducted from January, 2012, to January, 2016,at Cukurova University, Turkey, and comprised patients diagnosed with inflammatory bowel diseases and followed up at the Children Gastroenterology Department. By using molecular methods, 12 Mediterranean fevergene variants most frequently observed in the country were examined in all the diagnosed cases. The results were compared with age-matched healthy population data from the Genetic Diseases Diagnosis and Treatment Centre. Data was analysed using Graph Pad Prism. RESULTS: Of the 151 subjects, 46(30.4%) were cases and 105(69.5%) were controls. Among the cases, there were 23(50%) subjects with a mean age of 14.8±3 years who had ulcerative colitis, and 23(50%) with mean age 14.5±3.2 years who had Crohn's disease. The mean age of the controls was 16.4±3.2 years (p=0.716). Patients with ulcerative colitishad high frequencies of C allele in D102D T>C variant, G allele in G138G A>G variant, A allele in A165A C>A variant and A allele in R202Q G>A variant. Those with Crohn's disease frequently had wild type of R202Q G>A variant. Also, D102D T>C / R314R C>T haplotype was common at a certain level in the UC group. CONCLUSIONS: Mediterranean fever gene variant was more frequently found in cases with ulcerative colitis compared to the controls.


Assuntos
Colite Ulcerativa , Febre Familiar do Mediterrâneo , Doenças Inflamatórias Intestinais , Adolescente , Estudos de Casos e Controles , Criança , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/genética , Febre Familiar do Mediterrâneo/epidemiologia , Febre Familiar do Mediterrâneo/genética , Predisposição Genética para Doença , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Mutação , Polimorfismo Genético , Pirina/genética , Turquia/epidemiologia , Adulto Jovem
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