scholarly journals Unified Modeling of Familial Mediterranean Fever and Cryopyrin Associated Periodic Syndromes

2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
Yasemin Bozkurt ◽  
Alper Demir ◽  
Burak Erman ◽  
Ahmet Gül
Keyword(s):  
Familial Mediterranean Fever ◽  
Nonlinear Ordinary Differential Equations ◽  
Extensive Simulation ◽  
Unified Modeling ◽  
Caspase 1 ◽  
Hereditary Autoinflammatory Diseases ◽  
Clinical Observations ◽  
Genes Encoding ◽  
Mediterranean Fever ◽  
Simulation Results

Familial mediterranean fever (FMF) and Cryopyrin associated periodic syndromes (CAPS) are two prototypical hereditary autoinflammatory diseases, characterized by recurrent episodes of fever and inflammation as a result of mutations inMEFVandNLRP3genes encoding Pyrin and Cryopyrin proteins, respectively. Pyrin and Cryopyrin play key roles in the multiprotein inflammasome complex assembly, which regulates activity of an enzyme, Caspase 1, and its target cytokine, IL-1β. Overproduction of IL-1βby Caspase 1 is the main cause of episodic fever and inflammatory findings in FMF and CAPS. We present a unifying dynamical model for FMF and CAPS in the form of coupled nonlinear ordinary differential equations. The model is composed of two subsystems, which capture the interactions and dynamics of the key molecular players and the insults on the immune system. One of the subsystems, which contains a coupled positive-negative feedback motif, captures the dynamics of inflammation formation and regulation. We perform a comprehensive bifurcation analysis of the model and show that it exhibits three modes, capturing the Healthy, FMF, and CAPS cases. The mutations in Pyrin and Cryopyrin are reflected in the values of three parameters in the model. We present extensive simulation results for the model that match clinical observations.

scholarly journals Fiatal felnőtt korban diagnosztizált familiáris mediterrán láz

2020 ◽  
Vol 53 (4) ◽  
pp. 201-205
Author(s):  
Henrietta Poset ◽  
Judit Kárteszi ◽  
Tibor Kalmár ◽  
Zoltán Maróti ◽  
Julianna Fekete ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Clinical Symptoms ◽  
Clinical Status ◽  
Molecular Genetic ◽  
Mefv Gene ◽  
Young Female ◽  
C1 Inhibitor Deficiency ◽  
First Line Therapy ◽  
Hereditary Autoinflammatory Diseases ◽  
Mediterranean Fever

Összefoglaló. A familiáris mediterrán láz a herediter autoinflammatorikus betegségek közé tartozik. Klinikai tüneteit döntően a savós hártyák akut gyulladása (serositis: peritonitis, pleuritis, synovitis, ritkán pericarditis, meningitis) határozza meg. A betegség hátterében a pyrin fehérjét kódoló MEFV-gén többségében autoszómális recesszív módon öröklődő mutációi állnak. Legfontosabb szövődménye az amyloidosis, amely veseelégtelenséghez vezethet. Kezelésében első vonalbeli terápiaként a colchicin szerepel. Fiatal nőbetegünket 12 éves kora óta több intézetben vizsgálták intenzív hasi fájdalommal és lázzal járó attakok miatt. A tünettan részeként hányás, hasmenés és mellkasi fájdalom jelentkezett. A gyulladásos epizódok 5–14 napig tartottak, a köztes időszakokban viszont teljesen jól volt. A rohamok alatt készült laboratóriumi vizsgálatok során leukocitózis, valamint emelkedett süllyedés és CRP mutatkozott. Intravazális hemolízisre utalt az anémia, retikulocitózis, magas Sebi, szérum szabad hemoglobin és LDH együttes megjelenése. Az EKG-én inferior és az anteroseptalis elvezetésekben átmenetileg negatív T-hullámok jelentek meg, ami pericarditis lehetőségét vetette fel. Fizikális státuszából kiemelendő a diszkrét, de progrediáló splenomegalia. Kizártuk a porphyriat, glucose-6-phosphat dehydrogenase-hiányt, PNH-t és C1-inhibitorhiányt. Az autoinflammatorikus betegség miatt elvégzett molekuláris genetikai vizsgálat az MEFV-génmutáció homozigóta formáját, a Familiáris mediterrán láz diagnózisát igazolta. Summary. The familial Mediterranean fever is one of the hereditary autoinflammatory diseases. Its clinical symptoms are mainly determined by acute inflammation of the serous membranes (serositis: peritonitis, pleurisy, synovitis, rarely, pericarditis, meningitis). The background of the disease is mostly represented by autosomal recessively inherited mutations in the MEFV gene encoding the pyrine protein. Its most important complication is amyloidosis, which can lead to renal failure. Colchicine is included in its treatment, as a first-line therapy. Our young female patient has been examined in several institutions since the age of 12 for attacks of intense abdominal pain and fever. The symptoms included vomiting, diarrhea, and chest pain. The inflammatory episodes lasted 5–14 days, but in the intervening periods she was free of symptoms. Laboratory tests performed during the inflammatory periods showed leukocytosis as well as increased ESR and CRP. Intravascular hemolysis was indicated by anemia, reticulocytosis, co-occurrence of high Sebi, serum free hemoglobin and LDH. On the ECG, transiently negative T waves appeared in the inferior and anteroseptal leads, raising the possibility of pericarditis. Of her clinical status, discrete but progressive splenomegaly should be highlighted. Porphyria, glucose-6-phosphat dehydrogenase deficiency, PNH, and C1 inhibitor deficiency were excluded during our examinations. Molecular genetic testing urged by autoinflammatory disease confirmed a homozygous form of the MEFV gene mutation and established the diagnosis of familial Mediterranean fever.

scholarly journals The PRY/SPRY Domain of Pyrin/TRIM20, The Familial Mediterranean Fever Protein, Interacts with β2-Microglobulin to Promote Inflammasome Formation

2021 ◽  
Author(s):  
Sei Samukawa ◽  
Ryusuke Yoshimi ◽  
Yohei Kirino ◽  
Hideaki Nakajima
Keyword(s):  
Familial Mediterranean Fever ◽  
Protein Interactions ◽  
Hek293 Cells ◽  
Human Neutrophils ◽  
Interacting Protein ◽  
Hek 293 ◽  
Spry Domain ◽  
Caspase 1 ◽  
Associated Proteins ◽  
Mediterranean Fever

Abstract Background. Pyrin/TRIM20 is expressed in the neutrophils and monocytes/macrophages and regulates caspase-1 activation and interleukin-1β maturation. Although the mutations in the PRY/SPRY domain of pyrin cause familial Mediterranean fever (FMF), the mechanism of how mutated pyrin provokes excessive inflammation in FMF patients is not well understood. This study was undertaken to explore the new pyrin PRY/SPRY domain-binding protein and to investigate how the interaction affected the pyrin function.Methods. We carried out the yeast two-hybrid screening for pyrin PRY/SPRY domain-binding proteins. Then, protein interactions were investigated using Lenti-X 293T cells expressing pyrin-associated proteins by co-immunoprecipitation analysis. We also used human embryonic kidney (HEK) 293 cells expressing pyrin-associated proteins and human neutrophils stimulated with monosodium urate crystal for immunofluorescence staining analysis.Results. β2-Microglobulin (β2MG) was identified as the novel pyrin ligand binding to the PRY/SPRY domain. β2MG was co-localized with pyrin not only in the HEK293 cells overexpressing these proteins but also in the stimulated human neutrophils in the speck-like structures. The pyrin-β2MG interaction triggered the binding of pyrin and proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1) and then the subsequent recruitment of apoptosis-associated speck-like protein containing caspase recruitment domain (ASC). Caspase-1 p20 subunit, produced by pyrin inflammasome, also interacted with the pyrin PRY/SPRY domain and inhibited the pyrin-β2MG interaction. FMF-associated pyrin mutation M694V did not affect pyrin-β2MG interaction but weakened this inhibition.Conclusions. Our findings suggest that β2MG functions as the pyrin ligand inducing pyrin inflammasome formation and that the FMF-associated pyrin mutations weakened negative feedback of caspase-1 p20 subunit.

scholarly journals A clinical observation of hereditary spherocytosis in an elderly patient

2021 ◽  
Vol 2 (2) ◽  
pp. 100-103
Author(s):  
E. A. Burtseva ◽  
I V. Snezhko ◽  
G. Yu. Nagornaya ◽  
Yu. V. Shatokhin
Keyword(s):  
Elderly Patient ◽  
Early Diagnosis ◽  
Familial Mediterranean Fever ◽  
Genetic Disease ◽  
Clinical Observation ◽  
Hereditary Spherocytosis ◽  
Clinical Observations ◽  
Pathogenetic Therapy ◽  
Mediterranean Fever ◽  
Made In

Presented are three clinical observations of patients with a rare, but one of the oldest, genetic disease, which according to modern concepts belongs to the group of autoinflammatory diseases — familial Mediterranean fever. In the cases described, the diagnosis was first made in adulthood. The main purpose of the description of these cases is to draw the attention of practitioners to the possibility of early diagnosis and adequate pathogenetic therapy of this cohort of patients with an ethnic predisposition, but manifested regardless of the place of modern residence.

scholarly journals Abdominal syndrome in so-called «Outinflammatory diseases»; Two cases of family Mediterranean fever

2020 ◽  
pp. 121-125
Author(s):  
A. Yu. Spivakovskay ◽  
Yu. M. Spivakovskiy ◽  
Yu. V. Chernenkov
Keyword(s):  
Familial Mediterranean Fever ◽  
Clinical Symptoms ◽  
Inflammatory Diseases ◽  
Periodic Fever ◽  
Periodic Fever Syndrome ◽  
Clinical Observations ◽  
Auto Inflammatory Disease ◽  
Mediterranean Fever ◽  
The Moment ◽  
Clinical Cases

The aim — on the example of the analysis of clinical observations, the authors draw attention to various variants of the course of the classic auto — inflammatory disease-familial Mediterranean fever (SSL) with severe abdominal syndrome.Materials and methods: the article present clinical material on two observations of patients with SSL in clinical symptoms, which were dominated by abdominal syndrome, from the moment of their request for medical care to the verification of the diagnosis.Results: The article presents brief information about the diseases of the group of auto-inflammatory (periodic fever syndrome with mevalonatkinase deficiency, TRAPS-syndrome, Crohn’s disease, familial Mediterranean fever), in the manifestation of which gastroenterological symptoms play a significant role. An example of «early» and «late» diagnosis of auto-inflammatory diseases is illustrated by the results of the analysis of two clinical cases of patients with SSL.The analysis of the analyzed clinical cases confirms the multidisciplinary nature of the problem of auto-inflammatory diseases and the importance of readiness not only of rheumatologists, but also of other specialists to make such a diagnosis.

scholarly journals The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-κB through its N-terminal fragment

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1794-1803 ◽  
Author(s):  
Jae Jin Chae ◽  
Geryl Wood ◽  
Katharina Richard ◽  
Howard Jaffe ◽  
Nona T. Colburn ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Degradation Products ◽  
Adapter Protein ◽  
Caspase 1 ◽  
Terminal Fragment ◽  
Acid Protein ◽  
Mediterranean Fever ◽  
A Site ◽  
B30.2 Domain ◽  
Amino Acid Protein

Abstract Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in MEFV, which encodes a 781–amino acid protein denoted pyrin. We have previously shown that pyrin regulates caspase-1 activation and IL-1β production through interaction of its N-terminal PYD motif with the ASC adapter protein, and also modulates IL-1β production by interaction of its C-terminal B30.2 domain with the catalytic domains of caspase-1. We now asked whether pyrin might itself be a caspase-1 substrate, and found that pyrin is cleaved by caspase-1 at Asp330, a site remote from the B30.2 domain. Pyrin variants harboring FMF-associated B30.2 mutations were cleaved more efficiently than wild-type pyrin. The N-terminal cleaved fragment interacted with the p65 subunit of NF-κB and with IκB-α through its 15-aa bZIP basic domain and adjacent sequences, respectively, and translocated to the nucleus. The interaction of the N-terminal fragment with p65 enhanced entrance of p65 into the nucleus. The interaction of N-terminal pyrin with IκB-α induced calpain-mediated degradation of IκB-α, thus potentiating NF-κB activation. Absolute and relative quantities of cleaved pyrin and IκB-α degradation products were substantially increased in leukocytes from FMF patients compared with healthy controls. Our data support a new pyrin/caspase-1 pathway for NF-κB activation.

scholarly journals Three cases of late diagnosis of periodic illness

2021 ◽  
Vol 2 (2) ◽  
pp. 94-99
Author(s):  
L. N. Eliseeva ◽  
M. I. Bocharnikova
Keyword(s):  
Early Diagnosis ◽  
Familial Mediterranean Fever ◽  
Genetic Disease ◽  
Late Diagnosis ◽  
Autoinflammatory Diseases ◽  
Clinical Observations ◽  
Pathogenetic Therapy ◽  
Mediterranean Fever ◽  
Made In

Presented are three clinical observations of patients with a rare, but one of the oldest, genetic disease, which according to modern concepts belongs to the group of autoinflammatory diseases — familial Mediterranean fever. In the cases described, the diagnosis was first made in adulthood. The main purpose of the description of these cases is to draw the attention of practitioners to the possibility of early diagnosis and adequate pathogenetic therapy of this cohort of patients with an ethnic predisposition, but manifested regardless of the place of modern residence.

Sign in / Sign up

Export Citation Format

Share Document