scholarly journals 013. SUCCESSFUL USE OF TOCILIZUMAB IN TWO CASES OF SEVERE UNDEFINED AUTOINFLAMMATORY DISEASE WITH A SINGLE COPY OF THE MEDITERRANEAN FEVER GENE

Rheumatology ◽  
2017 ◽  
Vol 56 (suppl_2) ◽  
Author(s):  
Elena Nikiphorou ◽  
Vassos Neocleous ◽  
Leonidas A. Phylactou ◽  
Savvas Psarelis
Keyword(s):  
Autoinflammatory Disease ◽  
Single Copy ◽  
Mediterranean Fever ◽  
The Mediterranean

scholarly journals Successful use of tocilizumab in two cases of severe autoinflammatory disease with a single copy of the Mediterranean fever gene

Rheumatology ◽  
2017 ◽  
Vol 56 (9) ◽  
pp. 1627-1628 ◽  
Author(s):  
Elena Nikiphorou ◽  
Vassos Neocleous ◽  
Leonidas A. Phylactou ◽  
Savvas Psarelis
Keyword(s):  
Autoinflammatory Disease ◽  
Single Copy ◽  
Mediterranean Fever ◽  
The Mediterranean

scholarly journals Adaptation to Mediterranea

2020 ◽  
Author(s):  
Jelena M. Milenković ◽  
Dijana R. Stojanović ◽  
Jelena G. Najdanović
Keyword(s):  
Mediterranean Region ◽  
Autoinflammatory Disease ◽  
Mefv Gene ◽  
Regulatory Protein ◽  
Plasmodium Malariae ◽  
Immune Defense ◽  
Duffy Antigen ◽  
Mediterranean Fever ◽  
The Mediterranean ◽  
Glucose 6 Phosphate Dehydrogenase

The Mediterranean region encompasses countries that surround Mediterranean Sea. Due to its position at the intersection of Eurasia and Africa it has often been a route of human migrations during history, which contributed to its high biodiversity. People living in this area had been exposed to the episodes of natural selection that led to the establishment of specific genetic variations, for which is thought to carry a certain adaptation. Some recent studies have shown that genetic adaptations are probably related to the immune defense against infectious pathogens. One of the most recognizable disease of the region is familial Mediterranean fever (FMF), a prototype of a monogenic autoinflammatory disease. FMF is predisposed by the mutations in the Mediterranean fever (MEFV) gene that encodes inflammasome regulatory protein - pyrin. Specific variations of several other genes have been proposed to confer a protection against Plasmodium malariae parasite. Some of these are hemoglobin S (HbS), thalassemia, glucose-6-phosphate dehydrogenase deficiency, ovalocytosis, and mutation in the Duffy antigen (FY). In this chapter we will summarize important genetics and pathogenesis features of diseases commonly encountered in the Mediterranean region with a short discussion of potential adaptations that they may carry.

scholarly journals Abdominal syndrome in monogenic autoinflammatory disease – is it just a familial Mediterranean fever?

2020 ◽  
Vol 14 (4) ◽  
pp. 144-149
Author(s):  
S. O. Salugina ◽  
E. S. Fedorov ◽  
N. G. Volf
Keyword(s):  
Familial Mediterranean Fever ◽  
Autoinflammatory Disease ◽  
Bowel Perforation ◽  
Interleukin 1 ◽  
Diagnostic Features ◽  
Peritoneal Adhesions ◽  
Strict Adherence ◽  
Surgical Interventions ◽  
Abdominal Symptoms ◽  
Mediterranean Fever

Gastrointestinal (GI) manifestations, such as abdominal pain, nausea, vomiting, and diarrhea, are common autoinflammatory disease (AID) symptoms. The abdominal symptomatology reflecting serositis is one of the most important classification and diagnostic criteria for the classic monogenic AID (MAID) – familial Mediterranean fever (FMF). Failure to timely diagnose FMF frequently leads to unjustified surgical interventions. Other periodic fevers may also present as abdominal symptoms; however, the latter are outside their diagnostic features. These diseases include, first of all, tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Interleukin 1 (IL1) inhibitors serve as the major targeted drugs for the treatment of TRAPS. Russia has registered the IL1 inhibitor canakinumab that prevents the development of organ damages, including those in the GI tract. The paper describes a clinical case of the classic manifestations of TRAPS (fever, rash, periorbital edema, arthritis, and elevated levels of acutephase inflammatory markers) concurrent with severe abdominalgia during attacks and with the development of severe peritoneal adhesions, which led to bowel perforation and emergency surgical intervention. The prolonged persistence of inflammatory attacks before the initiation of therapy, as well as violation of the IL1 inhibitor administration regimen facilitated the development of an urgent exacerbation. Thus, TRAPS should be included in the differential diagnostic circle for patients with severe gastrointestinal manifestations characterized by an attack-like course. These patients need timely prescription of targeted therapy, strict adherence to the dosing and intervals between drug administrations, and careful monitoring to prevent serious complications with the visceral organs, including the gastrointestinal tract, and their immediate correction.

Two novel mutations R653H and E230K in the Mediterranean fever gene associated with disease

2001 ◽  
Vol 479 (1-2) ◽  
pp. 235-239 ◽  
Author(s):  
Christian Timmann ◽  
Birgit Muntau ◽  
Kathrin Kuhne ◽  
Annette Gelhaus ◽  
Rolf D. Horstmann
Keyword(s):  
Novel Mutations ◽  
Mediterranean Fever ◽  
The Mediterranean

scholarly journals Kawasaki disease triggered by EBV virus in a child with Familial Mediterranean Fever

2019 ◽  
Vol 45 (1) ◽  
Author(s):  
Maria Cristina Maggio ◽  
Carmelo Fabiano ◽  
Giovanni Corsello
Keyword(s):  
Kawasaki Disease ◽  
Familial Mediterranean Fever ◽  
Epstein Barr Virus ◽  
Autoinflammatory Disease ◽  
Mefv Gene ◽  
Clinical Manifestations ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Mediterranean Fever ◽  
Epstein Barr

Abstract Background Familial Mediterranean Fever is a monogenic autoinflammatory disease, secondary to mutation of MEFV gene, and typically expressed with recurrent attacks of fever, serositis, rash, aphthous changes in lips and/or oral mucosa. Kawasaki Disease, an acute systemic vasculitis with persistent fever (5 or more days), rash, stomatitis, conjunctivitis, lymphadenopathy, changes in extremities, is currently considered a multifactorial autoinflammatory disease. An infection, as Epstein Barr virus, can be the trigger of Kawasaki Disease. Case presentation We describe the clinical case of a 3-year-old boy with Kawasaki disease. Successfully treated with intravenous immune globulin, acetyl salicylate acid, he late developed anaemia and thrombocytopenia. The Epstein-Barr virus infection has been demonstrated and he showed a resolution of the clinical manifestations of Kawasaki disease with the persistence of coronaritis, without aneurisms. However, for the personal and familial history of monthly recurrent attacks of fever, pharyngitis, abdominal pain, the genetic study of MEFV was performed and demonstrated 3 heterozygous mutations of MEFV (E148Q, P369S, R408Q). Conclusions Mutations of MEFV can contribute to increase inflammatory expression in other diseases, as Kawasaki disease.

scholarly journals Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation

2016 ◽  
Vol 113 (50) ◽  
pp. 14384-14389 ◽  
Author(s):  
Hanne Van Gorp ◽  
Pedro H. V. Saavedra ◽  
Nathalia M. de Vasconcelos ◽  
Nina Van Opdenbosch ◽  
Lieselotte Vande Walle ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Autoinflammatory Disease ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Microtubule Assembly ◽  
Inflammasome Activation ◽  
Wild Type ◽  
Peripheral Blood Mononuclear ◽  
Mouse Macrophages ◽  
Mediterranean Fever

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is caused by mutations in the inflammasome adaptor Pyrin, but how FMF mutations alter signaling in FMF patients is unknown. Herein, we establish Clostridium difficile and its enterotoxin A (TcdA) as Pyrin-activating agents and show that wild-type and FMF Pyrin are differentially controlled by microtubules. Diverse microtubule assembly inhibitors prevented Pyrin-mediated caspase-1 activation and secretion of IL-1β and IL-18 from mouse macrophages and human peripheral blood mononuclear cells (PBMCs). Remarkably, Pyrin inflammasome activation persisted upon microtubule disassembly in PBMCs of FMF patients but not in cells of patients afflicted with other autoinflammatory diseases. We further demonstrate that microtubules control Pyrin activation downstream of Pyrin dephosphorylation and that FMF mutations enable microtubule-independent assembly of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) micrometer-sized perinuclear structures (specks). The discovery that Pyrin mutations remove the obligatory requirement for microtubules in inflammasome activation provides a conceptual framework for understanding FMF and enables immunological screening of FMF mutations.

scholarly journals Massive gene presence/absence variation in the mussel genome as an adaptive strategy: first evidence of a pan-genome in Metazoa

2019 ◽  
Author(s):  
Marco Gerdol ◽  
Rebeca Moreira ◽  
Fernando Cruz ◽  
Jessica Gómez-Garrido ◽  
Anna Vlasova ◽  
...  
Keyword(s):  
Large Scale ◽  
Single Copy ◽  
Genomic Diversity ◽  
Small Scale ◽  
Nucleotide Polymorphisms ◽  
Structural Variations ◽  
Pan Genome ◽  
Adaptive Value ◽  
Mediterranean Mussel ◽  
The Mediterranean

AbstractMussels are ecologically and economically relevant edible marine bivalves, highly invasive and resilient to biotic and abiotic stressors causing recurrent massive mortalities in other species. Here we show that the Mediterranean mussel Mytilus galloprovincialis has a complex pan-genomic architecture, which includes a core set of 45,000 genes shared by all individuals plus a surprisingly high number of dispensable genes (∼15,000). The latter are subject to presence/absence variation (PAV), i.e., they may be entirely missing in a given individual and, when present, they are frequently found as a single copy. The enrichment of dispensable genes in survival functions suggests an adaptive value for PAV, which might be the key to explain the extraordinary capabilities of adaptation and invasiveness of this species. Our study underpins a unique metazoan pan-genome architecture only previously described in prokaryotes and in a few non-metazoan eukaryotes, but that might also characterize other marine invertebrates.Significance statementIn animals, intraspecific genomic diversity is generally thought to derive from relatively small-scale variants, such as single nucleotide polymorphisms, small indels, duplications, inversions and translocations. On the other hand, large-scale structural variations which involve the loss of genomic regions encoding protein-coding genes in some individuals (i.e. presence/absence variation, PAV) have been so far only described in bacteria and, occasionally, in plants and fungi. Here we report the first evidence of a pan-genome in the animal kingdom, revealing that 25% of the genes of the Mediterranean mussel are subject to PAV. We show that this unique feature might have an adaptive value, due to the involvement of dispensable genes in functions related with defense and survival.

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