- Fas and Fas ligand gene polymorphisms in Turkish patients with Familial Mediterranean Fever. [Journal Article]
- GENEGene 2017 Apr 22
- Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterized by recurrent fever, serositis, abdominal pain, arthritis, arthralgia and erysipelas like erythema....
Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterized by recurrent fever, serositis, abdominal pain, arthritis, arthralgia and erysipelas like erythema. Fas and Fas ligand molecules play a central role in the apoptosis signaling of various cell types including neutrophils. Neutrophils are the major cell population involved in acute inflammation in patients with FMF and the role of Fas and Fas ligand molecules in this cells of FMF patients may be crucial. Therefore, in the present study, we aimed to investigate whether the Fas cell surface receptor gene (FAS); NM_000043.5: c.-671A>G (rs1800682, MvaI) and Fas ligand gene (FASLG), NM_000639.2: c.-844C>T (rs763110, BsrD1) functional polymorphisms in patients with FMF and their relation to the main clinical features of the disease. The polymorphisms in the promoter regions of FAS c.-671A>G and FASLG c.-844C>T were investigated in 97 non-related FMF patients and 70 non-related healthy controls by using PCR-RFLP technique. The frequencies of FAS c-671AG genotype and G allele were not significantly different between FMF patients and healthy subjects. The frequency of FASLG -844TC genotype was found significantly different between the patients with FMF and healthy controls whereas T or C allele frequency was not significantly different between the groups. Haplotype frequencies of the studied polymorphisms were also not significantly different between FMF patients and controls. There were no correlations between the studied FAS c.-671A>G and FASLG c.-844C>T polymorphisms and the main clinical features of FMF such as fever, arthritis, abdominal and chest pain, arthralgia and erysipelas-like erythema. Our findings suggest that FAS -671AG genotype or G allele and FASLG -844T allele are not to be a risk factor, whereas FASLG c.-844TC genotype may be protective in the studied Turkish population. According to our results we may suggest that although not statistically significant, higher frequencies of FASLG c.-844CC genotype in FMF patients may be related to delayed apoptosis of neutrophils and ultimately cause neutrophilic inflammation by increasing FASLG expression.
- Effect of familial Mediterranean fever on sexual and reproductive health in women. [Journal Article]
- TJTurk J Med Sci 2017 Apr 18; 47(2):463-469
- CONCLUSIONS: Familial Mediterranean fever is a rheumatic disease that predisposes patients to sexual dysfunction and premenstrual syndrome, which emerges as direct and indirect psychological factors.
- Monogenic Autoinflammatory Diseases with Mendelian Inheritance: Genes, Mutations, and Genotype/Phenotype Correlations. [Review]
- FIFront Immunol 2017; 8:344
- Autoinflammatory diseases (AIDs) are a genetically heterogeneous group of diseases caused by mutations of genes encoding proteins, which play a pivotal role in the regulation of the inflammatory resp...
Autoinflammatory diseases (AIDs) are a genetically heterogeneous group of diseases caused by mutations of genes encoding proteins, which play a pivotal role in the regulation of the inflammatory response. In the pathogenesis of AIDs, the role of the genetic background is triggered by environmental factors through the modulation of the innate immune system. Monogenic AIDs are characterized by Mendelian inheritance and are caused by highly penetrant genetic variants in single genes. During the last years, remarkable progress has been made in the identification of disease-associated genes by using new technologies, such as next-generation sequencing, which has allowed the genetic characterization in undiagnosed patients and in sporadic cases by means of targeted resequencing of a gene panel and whole exome sequencing. In this review, we delineate the genetics of the monogenic AIDs, report the role of the most common gene mutations, and describe the evidences of the most sound genotype/phenotype correlations in AID.
- Colchicine resistance and intolerance in familial mediterranean fever: Definition, causes, and alternative treatments. [Review]
- SASemin Arthritis Rheum 2017 Mar 20
- CONCLUSIONS: These results underscore the need to identify patients who are not optimally managed with colchicine and who might therefore benefit from additional biologic therapies.
- EFFECT OF FAMILIAL MEDITERRANEAN FEVER ON IVF OUTCOME: A RETROSPECTIVE CASE SERIES. [Journal Article]
- ACActa Clin Croat 2016; 55(2):254-8
- Although the in vitro fertilization-intra-cytoplasmic sperm injection (IVF-ICSI) has been utilized widely, the management in patients with an autoimmune disease is still a challenge. The aim of this ...
Although the in vitro fertilization-intra-cytoplasmic sperm injection (IVF-ICSI) has been utilized widely, the management in patients with an autoimmune disease is still a challenge. The aim of this study was to demonstrate IVF-ICSI outcomes in infertile women with familial Mediterranean fever (FMF). Patient data were collected from the cases registered from January 2006 until January 2014. A total of 6152 assisted reproductive technology (ART) cycles were analyzed retrospectively in the Ankara Zekai Tahir Burak Women’s Health Education and Research Hospital. Ten infertile women with FMF were included in the study. Baseline clinical and laboratory characteristics were collected and perinatal outcomes evaluated. T e mean age (years), duration of infertility (years) and body mass index (kg/m2) were 29.9±5.3, 5.7±5.3 and 27.9±5.7, respectively. The mean baseline follicle-stimulating hormone (FSH; IU/L), estradiol (E2; pg/mL) and antral follicle count were 7.0±2.4, 48.1±15.8 and 7.9±2.9, respectively. The distribution of ovarian response was heterogeneous. Fourteen cycles in ten patients were evaluated. Embryo transfer could be achieved in only ten cycles. Three out of ten patients became pregnant. No adverse perinatal outcome was observed. Our findings indicate that FMF might have no impact on ART cycles.
- Clinical update on inflammasomopathies. [Journal Article]
- IIInt Immunol 2017 Apr 06
- Inflammasomes are important elements of the innate immune defense. The most common autoinflammatory syndromes, as well a number of rare ones, are due to hereditary defects in the inflammasomes, hence...
Inflammasomes are important elements of the innate immune defense. The most common autoinflammatory syndromes, as well a number of rare ones, are due to hereditary defects in the inflammasomes, hence are called inflammasomopathies. The recent clinical advances in these diseases will be reviewed, with special emphasis on reflecting the international collaborative work in the field. Recent recommendations for familial Mediterranean fever (FMF), cryopyrin-associated periodic syndromes (CAPS) and hyper-IgD syndrome (HIDS) / mevalonate kinase deficiency (MKD) will be presented and diagnostics tests, treatment alternatives, and follow-up recommendations will be summarized. The other rare inflammasomopathies will be briefly discussed based on clinical features; these diseases are pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), NLRC4-related macrophage-activation syndrome of enterocolitis, mutations in NLRP12 that cause hereditary periodic fever syndromes (familial cold inflammatory syndrome 2), and NLRP1 associated autoinflammation with arthritis and dyskeratosis (NAIAD).
- Familial Mediterranean Fever: Recent Developments in Pathogenesis and New Recommendations for Management. [Review]
- FIFront Immunol 2017; 8:253
- Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin. The disease is characterized by...
Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin. The disease is characterized by self-limited inflammatory attacks of fever and polyserositis along with elevated acute phase reactants. FMF is inherited autosomal recessively; however, a significant proportion of heterozygotes also express the phenotype. FMF is caused by mutations in the MEFV gene coding for pyrin, which is a component of inflammasome functioning in inflammatory response and production of interleukin-1β (IL-1β). Recent studies have shown that pyrin recognizes bacterial modifications in Rho GTPases, which results in inflammasome activation and increase in IL-1β. Pyrin does not directly recognize Rho modification but probably affected by Rho effector kinase, which is a downstream event in the actin cytoskeleton pathway. Recently, an international group of experts has published the recommendations for the management of FMF. Colchicine is the mainstay of FMF treatment, and its regular use prevents attacks and controls subclinical inflammation in the majority of patients. Furthermore, it decreases the long-term risk of amyloidosis. However, a minority of FMF patients fail to response or tolerate colchicine treatment. Anti-interleukin-1 drugs could be considered in these patients. One should keep in mind the possibility of non-compliance in colchicine-non-responders. Although FMF is a relatively well-described AID and almost 20 years has passed since the discovery of the MEFV gene, there are still a number of unsolved problems about it such as the exact mechanism of the disease, symptomatic heterozygotes and their treatment, and the optimal management of colchicine resistance.
- Genetic and Epigenetic Determinants in Autoinflammatory Diseases. [Review]
- FIFront Immunol 2017; 8:318
- The concept of autoinflammation has evolved over the past 20 years, beginning with the discovery that mutations in the Mediterranean Fever (MEFV) gene were causative of Familial Mediterranean Fever. ...
The concept of autoinflammation has evolved over the past 20 years, beginning with the discovery that mutations in the Mediterranean Fever (MEFV) gene were causative of Familial Mediterranean Fever. Currently, autoinflammatory diseases comprise a wide range of disorders with the common features of recurrent fever attacks, prevalence of hyperreactive innate immune cells, and signs of inflammation that can be systemic or organ specific in the absence of pathogenic infection of autoimmunity. Innate immune cells from the myeloid compartment are the main effectors of uncontrolled inflammation that is caused in great extent by the overproduction of inflammatory cytokines such as IL-1β and IL-18. Defects in several signaling pathways that control innate immune defense, particularly the hyperreactivity of one or more inflammasomes, are at the core of pathologic autoinflammatory phenotypes. Although many of the autoinflammatory syndromes are known to be monogenic, some of them are genetically complex and are impacted by environmental factors. Recently, epigenetic dysregulation has surfaced as an additional contributor to pathogenesis. In the present review, we discuss data that are currently available to describe the contribution of epigenetic mechanisms in autoinflammatory diseases.
- Tofacitinib suppresses disease activity and febrile attacks in a patient with coexisting rheumatoid arthritis and familial Mediterranean fever. [Journal Article]
- ARActa Reumatol Port 2017 Jan-Mar; 42(1):88-90
- Familial Mediterranean fever (FMF) is the most common hereditary auto-inflammatory (periodic fever) syndrome, and usually successfully treated with colchicine. However, nearly 5-10% of FMF cases are ...
Familial Mediterranean fever (FMF) is the most common hereditary auto-inflammatory (periodic fever) syndrome, and usually successfully treated with colchicine. However, nearly 5-10% of FMF cases are resistant or intolerant to colchicine and treatment options are highly restricted in these cases. Biologics including anakinra, canakinumab, rilonacept, etanercept, infliximab, interferon-alpha, and tocilizumab are shown to have efficacy to control FMF attacks. Tofacitinib, a Janus kinase (JAK) inhibitor, is an orally administered non-biologic disease modifying anti-rheumatic drug for the treatment of rheumatoid arthritis (RA). Herein we report a female patient with coexisting RA and colchicine resistant FMF whose FMF attacks and disease activity were completely controlled after treatment with tofacitinib, a small-molecule JAK3 inhibitor.
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- Genetic Analysis of Southwestern Iranian Patients with Familial Mediterranean Fever. [Journal Article]
- RBRep Biochem Mol Biol 2017; 5(2):117-120
- CONCLUSIONS: Although none of the 12 mutations we included in our test panel was detected in 60% of our patients, all of them had FMF symptoms and responded well to colchicine. MEFV full gene sequencing analysis in these patients may lead to finding new mutations in southwestern Iranian FMF patients which would be helpful in designing a local diagnostic kit.