Experimental models in Familial Mediterranean Fever (FMF): Insights into pathophysiology and therapeutic strategies.

Familial Mediterranean Fever (FMF) is a recurrent polyserositis characterized by self-limiting episodes or attacks of fever along with serosal inflammation. It mainly impacts people of the Mediterranean and Middle Eastern basin. FMF is a recessive autoinflammatory condition caused by mutation in the MEFV gene located on chromosome 16p13. MEFV mutations lead to the activation of the pyrin inflammasome resulting in an uncontrolled release of IL-1ß. Various in vitro, in vivo and ex vivo experimental models have been developed to further comprehend the etiology and pathogenesis of FMF. These models have been proven to be clinically relevant to human FMF and can provide significant information about biological systems with respect to this condition. Additionally, these models have provided pertinent contributions to the development of potent therapeutic strategies against FMF. In this review, we describe the different experimental models utilized in FMF and we focus primarily on the most widely used models that have produced prominent insights into the pathophysiology of the disease.

The effect of education given to Turkish adolescents with Familial Mediterranean fever on anxiety, depression, and quality of life.

To examine the effects of individual education given to Turkish adolescents with Familial Mediterranean fever (FMF) on anxiety, depression, and quality of life. The randomized controlled experimental study was performed on 70 adolescents aged 12-18 years who were diagnosed as having FMF between October 2021 and April 2022 in Turkey. The disease management education was offered individually to adolescents in the intervention group with a booklet entitled "FMF is under my control;" no intervention was applied to adolescents in the control group. The training booklet was prepared by the researchers in a multidisciplinary team and was finalized by taking expert opinions. In the data collection process, a personal information form, the State-Trait Anxiety Inventory for Children (STAI-CH), the children's depression inventory (CDI), and the Pediatric Quality of Life Inventory (PedsQL) were used. After applying the scales specified in the pretest, individual training was given and the posttest was performed 2 months later using the same scales. After the education, there was a statistically significant decrease in the mean CDI score of the intervention group (p < 0.05), whereas there were statistically significant increases in mean scores obtained on PedsQL and its sub-scales (p < 0.05). However, the decrease in the mean STAI-CH score of the intervention group was not statistically significant (p > 0.05). There was no statistically significant difference in the mean STAI-CH, CDI, and PedsQL scores of the control group after the education (p > 0.05).  Conclusion: The effectiveness of the individual education program for adolescents with FMF in improving quality of life and reducing levels of depression within the scope of disease management has been confirmed. It is recommended that all health professionals working with children with FMF regularly provide individual or group-planned education programs. What is Known: • The unpredictability of FMF attacks has a very negative effect on adolescents. • Individual education programs on FMF focus on children with a holistic approach. What is New: • To the best of our knowledge, this study is the first study to evaluate disease management education given to adolescents with FMF. • This is a pioneering study of the use of nurses in the education of adolescents with FMF and in fulfilling their educational roles.

[Monogenic autoinflammatory diseases. An introduction on a translational mode to]. / Maladies auto-inflammatoires monogéniques. Une introduction sur un mode translationnel aux inflammasomopathies.

Autoinflammatory diseases refer to a broad spectrum of diseases that are primarily due to an abnormality in the regulation of natural immunity. Some are polygenic and highly influenced by the environment, others are monogenic. This article is devoted to a family of monogenic autoinflammatory diseases that is very important because it includes the emblematic Mediterranean familial fever, the first autoinflammatory disease described as such and which heavily affects the Eastern Mediterranean populations. We will discuss the regulatory mechanisms of inflammasomes and the impact of certain mutations on their function. General principles of treatment and diagnosis will also be discussed. Other autoinflammatory diseases (including type 1 interferonopathies and NF-?b and TNF-? axis abnormalities) deserve to be discussed later on.

: Les maladies auto-inflammatoires désignent une vaste gamme de maladies dues, avant tout, à une anomalie de régulation de l'immunité naturelle. Certaines sont polygéniques et très influencées par l'environnement, d'autres sont monogéniques. Cet article est consacré à une famille de maladies auto-inflammatoires monogéniques très importante car elle comprend l'emblématique fièvre familiale méditerranéenne, la première maladie auto- inflammatoire décrite comme telle et qui touche lourdement les populations de l'Est de la Méditerranée. Nous aborderons les mécanismes de régulation des inflammasomes et l'impact de certaines mutations sur leur fonctionnement. Les principes généraux du traitement et du diagnostic seront aussi abordés. Les autres maladies auto- inflammatoires, dont les interféronopathies de type 1 et les anomalies de l'axe NF-?b et du TNF-?, mériteraient d'être traitées ultérieurement.

Contribution of Arab Countries to Familial Mediterranean Fever Research: a PubMed-based bibliometric analysis.

Familial Mediterranean Fever (FMF) is an inherited autoinflammatory disease. One of the feared complications of FMF, amyloidosis is often correlated with an increased mortality rate. The severity of the disease is linked with different mutations in the MEFV gene that may favor different outcomes (amyloidosis, Bechet's disease…). Although several countries worldwide contribute remarkably to research related to FMF, Arab countries make up only a small part of this contribution. This study aims to estimate numerically the contribution of the Arab world to research conducted on FMF. PubMed is used to quantitate the number of FMF-related articles published by each Arab country from 2004 till 2019. The retrieved numbers are normalized with respect to each country's average population and average Gross Domestic Product (GDP) and are also compared to those of some non-Arab countries having high FMF prevalence. In comparison with some non-Arab countries, the Arab world has a minor contribution of 3.80% to the total FMF-related publications, faced by 24.93% solely by Turkey. Out of total research done by Arab countries, FMF-related articles constitute no more than 0.133%. When normalized against the average population, Tunisia ranks first, followed by Lebanon. Similarly, normalizing the retrieved numbers of articles against average GDP shows that Tunisia and Lebanon come first and second, respectively. Only 8 Arab countries published a total of 13 articles concerning amyloidosis which makes 4.7% of the total Arabic FMF published articles. This study reflects an undoubtable need for more research to be conducted on FMF by the Arab countries, which suffer greatly from immense shortage in research productivity, due to the many obstacles and limitations these countries face every day.

The Effect of Immunobiotic/Psychobiotic Lactobacillus acidophilus Strain INMIA 9602 Er 317/402 Narine on Gut Prevotella in Familial Mediterranean Fever: Gender-Associated Effects.

Possible mechanisms involved in sex-dependent differences in the gut microbiota have a growing interest worldwide, but the effects of probiotics dependence on the gender of the host have remained outside of researchers' attention until now. Previously, our research data described gender-specific differences in the gut microbiota of Armenian Familial Mediterranean fever (FMF) patients. Taking into account the possible association of Prevotella spp. with depressive disorders, the aim of the current investigations was an evaluation of changes in the abundance of gut Prevotella of FMF patients in association with the patient's depression and gender. The differences between healthy and FMF diseased gut microbiota in terms of Prevotella abundance were revealed. In addition, the gender-dependent effects of immunobiotic/psychobiotic Narine on the abundance of gut Prevotella of FMF patients and patients' depression scores were shown by us in this study.

Association of complementary and integrative therapy use and symptoms among Turkish patients with familial Mediterranean fever.

OBJECTIVE: This study explored the correlations between the use of complementary and integrative therapies (CITs) and symptoms among Turkish patients with familial Mediterranean fever (FMF). METHODS: This is a cross-sectional and descriptive study. The study was conducted with 1119 FMF patients who were registered to the social networking site for Behcet's and the FMF Patients Association (Befemder) in Turkey, between January 2018 and February 2019. Data were collected using an online survey, for which a three-part questionnaire was created using a Google form. Descriptive statistics, chi-square test and logistic regression analysis were used to analyze the data. RESULTS: It was determined that 53.2% of the individuals who participated in the research used various forms of CITs and that 32.8% used vitamin and mineral supplements (calcium, iron, and vitamin B12, C and D), 25.0% used nutritional supplements (fish oil and honey), and 24.6% used oral herbs (ginger, turmeric, green tea and rosemary) and mind-body methods (relaxation, respiration exercise and meditation). It was determined that the percentage of participants that used CITs was higher among women (odds ratio [OR] = 1.825; 95% confidence interval [CI] 1.421-2.344), those with joint pain (OR = 1.385; 95% CI 1.047-1.832), those with difficulty breathing (OR = 1.323; 95% CI 1.031-1.697), those with gastrointestinal symptoms (OR = 1.405; 95% CI 1.089-1.814) and those who had a family member with FMF (OR = 1.437; 95% CI 1.115-1.851). CONCLUSION: More than half of the individuals used at least one type of CIT for symptom control.

Evaluation of caregiver burden and coping strategies in parents of paediatric familial Mediterranean fever patients in relation to illness severity, therapy and health-related quality of life.

PURPOSE: The study aimed to determine the caregiver burden and coping strategies in caregivers of familial Mediterranean fever (FMF) patients in relation to illness severity, therapy and health-related quality of life (HRQoL). METHODS: The study included 171 paediatric FMF patients and their caregivers (parents). The caregivers were asked to complete a socio-demographic form, the Zarit caregiver burden interview (ZCBI) and the Brief COPE. The patients and their caregivers were asked to complete the KINDer Lebensqualitätsfragebogen questionnaire (self-report and proxy report, respectively) for assessing HRQoL. The patients were categorised according to their disease activity (mild, moderate or severe) and the presence or absence of anti-IL-1 therapy. RESULTS: The mean ZCBI score of the caregivers was 44.7 ± 13.5. ZCBI and COPE scores did not differ significantly between the caregivers of FMF patients receiving and not receiving anti-IL-1 therapy. However, dysfunctional COPE (p = 0.039) and ZCBI (p = 0.021) scores showed a significant difference between the caregivers in relation to patient's disease severity. ZCBI scores were positively correlated with dysfunctional coping (p = 0.01). Self-reported HRQoL disease module scores were lower for the patients who received anti-IL-1 therapy than for those did not (p = 0.009). Proxy-reported (p < 0.001) and self-reported (p = 0.043) HRQoL disease module scores were lower for the patients with severe disease activity. CONCLUSIONS: As the caregiver burden increases, parents tend to use a dysfunctional coping strategy. Good control of disease activity with administration of medical therapy can reduce the disease severity, thereby decrease the caregiver burden, and secondly help to reduce the usage of dysfunctional coping in caregivers.

Twenty-Year Experience of a Single Referral Center on Pediatric Familial Mediterranean Fever: What Has Changed Over the Last Decade?

BACKGROUND/OBJECTIVE: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease and is characterized by recurrent fever and serositis episodes. We aimed to share our 20-year FMF experience, clarify a phenotype-genotype correlation, and compare the characteristics and outcomes of pediatric FMF patients over the last 2 decades in this study. METHODS: This medical record review study included 714 pediatric FMF patients (340 females, 374 males), diagnosed by Tel Hashomer diagnostic criteria between January 2009 and January 2019 and followed up in our department. Demographic and disease characteristics, obtained from medical records of the patients, were compared between patients with M694V homozygosity and other genotypes and showed whether they were diagnosed before (n = 137) or after January 2010 (n = 577). χ2, Student t, and Mann-Whitney U tests were used to compare categorical and continuous variables between these groups. RESULTS: The most common symptoms were abdominal pain (92%), fever (89.5%), and arthralgia (64.5%). Mean ages at symptom onset and diagnosis were 5.16 ± 3.73 and 7.71 ± 3.87 years, respectively. M694V homozygosity was recorded in 111 patients (15.5%). Fever, arthralgia, arthritis, myalgia, erysipela-like erythema, colchicine resistance, and subclinical inflammation were more frequent, and mean disease severity score was higher in patients with M694V homozygosity. Fever, chest pain, and proteinuria were statistically more frequent in patients diagnosed before January 2010. Although M694V homozygosity rate was similar, patients diagnosed in the last decade had lower mean disease severity score. CONCLUSIONS: With this study, we speculate that although genotype and delay in diagnosis were similar, patients diagnosed in the last decade have a milder disease severity.

Association of complementary and integrative therapy use and symptoms among Turkish patients with familial Mediterranean fever / 中西医结合学报

OBJECTIVE@#This study explored the correlations between the use of complementary and integrative therapies (CITs) and symptoms among Turkish patients with familial Mediterranean fever (FMF).@*METHODS@#This is a cross-sectional and descriptive study. The study was conducted with 1119 FMF patients who were registered to the social networking site for Behcet's and the FMF Patients Association (Befemder) in Turkey, between January 2018 and February 2019. Data were collected using an online survey, for which a three-part questionnaire was created using a Google form. Descriptive statistics, chi-square test and logistic regression analysis were used to analyze the data.@*RESULTS@#It was determined that 53.2% of the individuals who participated in the research used various forms of CITs and that 32.8% used vitamin and mineral supplements (calcium, iron, and vitamin B12, C and D), 25.0% used nutritional supplements (fish oil and honey), and 24.6% used oral herbs (ginger, turmeric, green tea and rosemary) and mind-body methods (relaxation, respiration exercise and meditation). It was determined that the percentage of participants that used CITs was higher among women (odds ratio [OR] = 1.825; 95% confidence interval [CI] 1.421-2.344), those with joint pain (OR = 1.385; 95% CI 1.047-1.832), those with difficulty breathing (OR = 1.323; 95% CI 1.031-1.697), those with gastrointestinal symptoms (OR = 1.405; 95% CI 1.089-1.814) and those who had a family member with FMF (OR = 1.437; 95% CI 1.115-1.851).@*CONCLUSION@#More than half of the individuals used at least one type of CIT for symptom control.

Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review

Familial Mediterranean fever (FMF) (OMIM #249100) is the most common hereditary autoinflammatory disease in the world. FMF is caused by gain of function mutations of MEFV gene which encodes an immune regulatory protein, pyrin. Over the last few years, we have witnessed several new developments in the pathogenesis, genetic testing, diagnosis, comorbidities, disease related damage and treatment approaches to FMF. Elucidation of some of the pathogenic mechanisms has led to the discovery of pathways involved in inflammatory, metabolic, cardiovascular and degenerative diseases. The use of next generation sequencing in FMF has revealed many new gene variants whose clinical significance may be clarified by developing functional assays and biomarkers. Clinically, although FMF is considered an episodic disease characterized by brief attacks, recent systematic studies have defined several associated chronic inflammatory conditions. Colchicine is the mainstay of FMF treatment, and interleukin (IL)-1 antagonists are the treatment of choice in refractory or intolerant cases. Experience of IL-1 antagonists, anakinra and canakinumab, is now available in thousands of colchicine resistant or intolerant FMF patients. In this contemporary review, we surveyed current FMF knowledge in the light of these recent advances.

A systematic literature review of efficacy, effectiveness and safety of biologic therapies for treatment of familial Mediterranean fever.

OBJECTIVES: To identify and summarize the existing evidence on the efficacy, effectiveness and safety of biologic therapies used, either as indicated or off-label, in the treatment of FMF. METHODS: A systematic literature review was conducted using Embase®, MEDLINE®, MEDLINE®-In Process, and Cochrane databases to identify randomized/non-randomized controlled trials (RCTs/non-RCTs) and real-world observational studies of FMF published as full-text articles (2000-September 2017) or conference abstracts (2014-September 2017). Studies with data for ≥1 biologic were included. Studies with <5 patients were excluded. RESULTS: Of the 3342 retrieved records, 67 publications, yielding 38 unique studies, were included. All studies were published after the year 2010, and the majority (21) were full-text articles. Most studies (33/38) were prospective/retrospective observational; three were double-blind, placebo-controlled RCTs (one each of anakinra, canakinumab and rilonacept); and two were non-RCTs (both canakinumab). Anakinra (26), canakinumab (21) and etanercept (6) were the most frequently used biologics across studies, whereas use of adalimumab, tocilizumab, rilonacept and infliximab was limited (1-2 studies). The available evidence suggested benefits of anakinra and canakinumab in FMF. CONCLUSION: Anti-IL-1 therapies (i.e. anakinra and canakinumab) appear to be effective and safe options in the treatment of overall FMF, including patients with colchicine resistance and FMF-related amyloidosis. There is a need for properly designed prospective or controlled studies to conclude the superiority of one anti-IL-1 therapy over another. Evidence on the use of TNF-α and IL-6 inhibitors is limited, and further research is suggested.

Anti-IL1 treatment in colchicine-resistant paediatric FMF patients: real life data from the HELIOS registry.

OBJECTIVES: FMF is a prototype of autoinflammatory diseases associated with excess IL1 production. Anti-IL1 treatments are the first-line alternatives in colchicine-resistant/intolerant FMF patients. We aimed to investigate the efficacy and safety of anti-IL1 treatment in paediatric FMF patients in our local [Hacettepe univErsity eLectronIc research fOrmS (HELIOS)] registry. METHODS: HELIOS is a web-based biologic drug registry for paediatric rheumatology patients. We have analysed the clinical features, disease activity parameters, treatment responses and safety outcomes in FMF patients treated with anti-IL1 agents. RESULTS: Forty paediatric FMF patients (34 continuous and six on-demand use) were included. Among the continuously treated group (61.7% female), the mean age at the start of colchicine was 5.55 (3.87) years. Age at onset of the anti-IL1 treatment was 11.47 (5.41) years with a mean follow-up duration of 3.87 (1.96) years. Apart from two, all patients had biallelic exon-10 mutations. We also gave anti-IL1 treatment on an on-demand basis in six patients. Anakinra was used as the first-line anti-IL1 treatment. During the last visit, six patients were treated with anakinra and 28 patients with canakinumab. Anti-IL1 treatment decreased the CRP levels and number and severity of the attacks. There were three hospitalizations reported due to mild infections. Eleven patients had local skin reactions, two patients had leucopenia with anakinra and one patient had thrombocytopenia with canakinumab. There was no malignancy or other severe adverse reactions. CONCLUSION: Anakinra and canakinumab are efficient and safe alternatives in colchicine-resistant or -intolerant paediatric FMF patients. We also, for the first time, report on-demand use of anti-IL1 in paediatric FMF patients.

Necessity of Utilizing Physiological Glucocorticoids for Managing Familial Mediterranean Fever.

BACKGROUND Familial Mediterranean fever is an auto-inflammatory disease caused by pyrin mutations. Glucocorticoids inhibit the production and secretion of inflammatory cytokines, including IL-6 and IL-1ß, from inflammatory cells and suppress the activation of nuclear factor-kappaB in the nucleus. However, the functions of physiological glucocorticoids in the disease remain unknown. CASE REPORT We report the case of a Japanese man with familial Mediterranean fever complicated by isolated adrenocorticotropic hormone deficiency. Patient non-compliance with hydrocortisone replacement therapy led to a series of pericarditis and fever episodes. Subsequently, the regular administration of colchicine alone could not prevent auto-inflammation. The clinical course of treatment suggested that the absence of physiological levels of glucocorticoids is crucial for familial Mediterranean fever attacks. Because familial Mediterranean fever is a pyrin abnormality-induced auto-inflammatory disease that subsequently activates cytokines via the nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing 3 inflammasomes and the absence of glucocorticoids can exacerbate the severity of the auto-inflammatory disease. CONCLUSIONS Physiological glucocorticoid levels appear to be essential for the regulation of inflammasome activation via IL-6-negative regulation. However, pharmacological levels of glucocorticoids are not currently used for the prevention of familial Mediterranean fever attacks. Physicians should be aware of adrenal insufficiency as a possible disorder when they encounter cases of refractory familial Mediterranean fever.

FMF is not always "fever": from clinical presentation to "treat to target".

Familial Mediterranean Fever, a monogenic autoinflammatory disease secondary to MEFV gene mutations in the chromosome 16p13, is characterized by recurrent self-limiting attacks of fever, arthritis, aphthous changes in lips and/or oral mucosa, erythema, serositis. It is caused by dysregulation of the inflammasome, a complex intracellular multiprotein structure, commanding the overproduction of interleukin 1. Familial Mediterranean Fever can be associated with other multifactorial autoinflammatory diseases, as vasculitis and Behçet disease.Symptoms frequently start before 20 years of age and are characterized by a more severe phenotype in patients who begin earlier.Attacks consist of fever, serositis, arthritis and high levels of inflammatory reactants: C-reactive protein, erythrocyte sedimentation rate, serum amyloid A associated with leucocytosis and neutrophilia. The symptom-free intervals are of different length.The attacks of Familial Mediterranean Fever can have a trigger, as infections, stress, menses, exposure to cold, fat-rich food, drugs.The diagnosis needs a clinical definition of the disease and a genetic confirmation. An accurate differential diagnosis is mandatory to exclude infective agents, autoimmune diseases, etc.In many patients there is no genetic confirmation of the disease; furthermore, some subjects with the relieve of MEFV mutations, show a phenotype not in line with the diagnosis of Familial Mediterranean Fever. For these reasons, diagnostic criteria were developed, as Tel Hashomer Hospital criteria, the "Turkish FMF Paediatric criteria", the "clinical classification criteria for autoinflammatory periodic fevers" formulated by PRINTO.The goals of the treatment are: prevention of attacks recurrence, normalization of inflammatory markers, control of subclinical inflammation in attacks-free intervals and prevention of medium and long-term complications, as amyloidosis. Colchicine is the first step in the treatment; biological drugs are effective in non-responder patients.The goal of this paper is to give a wide and broad review to general paediatricians on Familial Mediterranean Fever, with the relative diagnostic, clinical and therapeutic aspects.

Improvement of MEFV gene variants classification to aid treatment decision making in familial Mediterranean fever.

OBJECTIVE: FMF is an inherited autoinflammatory syndrome caused by mutations in the MEFV gene. MEFV variants are still largely classified as acvariant of uncertain significance, or with unresolved classification, posing significant challenges in FMF diagnosis. Rare Exome Variant Ensemble Learner (REVEL) is a recently developed variant metapredictor tool. To reduce the number of MEFV variants with ambiguous classification, we extracted REVEL scores for all missense variants present in the INFEVERS database, and analysed its correlation with expert-based classification and localization in the MEFV-encoded pyrin functional domains. METHODS: The data set of 216 MEFV missense variants was divided into four categories (likely benign, variant of uncertain significance, likely pathogenic and unresolved). Variants were plotted onto the pyrin protein, the distribution of REVEL scores in each category was computed and means, confidence intervals, and area under the receiver operating curve were calculated. RESULTS: We observed a non-random distribution of pathogenic variants along the pyrin functional domains. The REVEL scores demonstrated a good correlation with the consensus classification of the International Study Group for Systemic Autoinflammatory Diseases. Sensitivity, specificity and accuracy were calculated for different cut-off values of REVEL scores and a gene-specific-threshold of 0.298 was computed with confidence boundary limits. This cut-off value allowed us to propose a reclassification of 96 MEFV gene variants, thus reducing the variant of uncertain significance proportion from 61.6% to 17.6%. CONCLUSION: The combination of available expert information with sensitive predictor tools could result in a more accurate interpretation of clinical consequences of MEFV gene variants, and to a better genetic counselling and patient management.

Autoinflammation: Lessons from the study of familial Mediterranean fever.

Autoinflammatory disorders represent a heterogeneous group of systemic inflammatory diseases caused by genetic or acquired defects in key components of the innate immunity. Familial Mediterranean fever (FMF) is the most common among the other clinical phenotypes of the rare hereditary periodic fevers (HPFs) syndromes. FMF is associated with mutations in the MEFV gene encoding pyrin and is characterized by recurrent, often stress-provoked attacks of fever and serositis, but sometimes also by chronic subclinical inflammation. FMF is prevalent in Greece and other countries of the eastern Mediterranean region. Over the last 17 years, our group has focused on FMF as a model suitable for the research on innate immunity and particularly the role of neutrophils. Therefore, the study of Greek patients with FMF has yielded lessons across several levels: the epidemiology of the disease in Greece, the spectrum of its clinical manifestations and potential overlaps with other idiopathic inflammatory conditions, the demonstration of its rather complex and heterogeneous genetic background and the suggestion of a novel mechanism involved in the crosstalk between environmental stress and inflammation. Mechanistically, during FMF attack, neutrophils release chromatin structures called neutrophil extracellular traps (NETs), which are decorated with bioactive IL-1ß. REDD1 (regulated in development and DNA damage responses 1), that encodes a stress-related mTOR repressor, has been found to be the most significantly upregulated gene in neutrophils during disease attacks. Upon adrenergic stress, REDD1-induced autophagy triggers a pyrin-driven IL-1ß maturation, and the release of IL-1ß-bearing NETs. Consequently, not only the mode of action of IL-1ß-targeting therapies is explained, but also new treatment prospects emerge with the evaluation of old or the design of new drugs targeting autophagy-induced NETosis. Information gained from FMF studies may subsequently be applied in more complex but still relevant inflammatory conditions, such as adult-onset Still's disease, gout, ulcerative colitis and Behçet's disease.

Potential of miRNAs to predict and treat inflammation from the perspective of Familial Mediterranean Fever.

AIM: microRNAs (miRNAs) are small noncoding RNAs that play critical roles in physiological networks by regulating host genome expression at the post-transcriptional level. miRNAs are known to be key regulators of various biological processes in different types of immune cells, and they are known to regulate immunological functions. Differential expression of miRNAs has been documented in several diseases, including autoinflammatory and autoimmune diseases. This review aimed to focus on miRNAs and their association with autoimmune and autoinflammatory diseases. METHODS: All related literature was screened from PubMed, and we discussed the possible role of miRNAs in disease prediction and usage as therapeutic agents from the perspective of Familial Mediterranean Fever (FMF). CONCLUSIONS: FMF is an inherited autosomal recessive autoinflammatory disease caused by mutations in the MEditerranean FeVer (MEFV) gene, which encodes the protein pyrin. Recent studies have demonstrated that miRNAs may be effective in the pathogenesis of FMF and offer a potential explanation for phenotypic heterogeneity. Further understanding of the role of miRNAs in the pathogenesis of these diseases may help to identify molecular diagnostic markers, which may be important for the differential diagnosis of autoinflammatory diseases. Studies have shown that in the near future, traditional therapies in autoinflammatory diseases may be replaced with novel effective, miRNA-based therapies, such as the delivery of miRNA mimics or antagonists. These approaches may be important for predictive, preventive, and personalized medicine.

Familial Mediterranean Fever (FMF): a single centre retrospective study in Amsterdam.

BACKGROUND: Familial Mediterranean Fever (FMF) is the earliest described and most prevalent hereditary auto-inflammatory disease. Its clinical presentation is diverse, leading to possible delay in diagnosis and treatment. Due to immigration, FMF became common in non-Mediterranean European regions. In the present single centre retrospective study, the clinical, demographic, and genetic characteristics of patients with FMF of different ancestry in Amsterdam are described. METHODS: Case records of patients with FMF, who met the Tel-Hashomer diagnostic criteria, were retrospectively analysed. The international disease severity score was used. RESULTS: Between 1990-2012, 53 patients were identified, 28 were female. Main country of origin was Turkey. The mean age at the time of analysis was 29.1 years; 13.8 years at onset of symptoms; and at time of diagnosis, 22.0 years. Most frequent symptoms were peritonitis (91%) and fever (81%). The mean C-reactive protein and erythrocyte sedimentation rate during acute attacks were 133 mg/l and 37 mm/first hour, respectively. One patient developed amyloidosis as a complication. Seventeen patients underwent abdominal surgery before diagnosis. Most patients (92%) received colchicine treatment and were responsive (81%). Most patients classified their disease as a mild disease (42%). MEFV gene mutation analysis was performed in 46 patients; most patients were compound heterozygotes (n = 17), and the most frequent mutation was M694V (n = 18). CONCLUSION: FMF in Amsterdam is diagnosed in relatively young patients and the delay to diagnosis is 8.2 years. Disease manifestations and genetic distribution of our FMF patients are comparable to those in Mediterranean regions, suggesting that ancestry is more important than environment.

Evaluation of the Burden of Care and the Quality of Life in the Parents of Turkish Children with Familial Mediterranean Fever.

PURPOSE: This study aimed to determine the burden of care and the quality of life in caregivers of children with FMF. DESIGN AND METHODS: A cross-sectional study was conducted. Caregivers of the 109 children with FMF followed by a pediatric nephrology department were invited to join the study. Besides demographic information, the Zarit Care Burden Scale (ZCBS) and the World Health Organization Quality of Life Questionnaire-Short Form (WHOQOL-BREF) were used to collect data. Results for 90 patients were analyzed. RESULTS: The mean (±SD) ZCBS score of the caregivers was 44.78 ±â€¯13.55. Care burden of the caregivers according to the ZCBS was categorized as; 61.1% (n = 55) mild, 25.6% (n = 23) moderate, and 13.3% (n = 12) severe. Although single caregivers were perceived as having a relatively higher burden than those who were married (80% and 36%), this difference was not significant. There were no statistically significant differences between ZCBS categories concerning caregivers' gender, educational status, and having comorbidities (p > 0.05). Also, there were no significant correlations between ZCBS and the WHOQOL-BREF domains (p > 0.05). CONCLUSION: This study showed that the quality of life of the caregivers of children with FMF was not adversely affected, but a significant number of caregivers perceived care burden in moderate severity. Attention should be paid to the needs of caregivers, and they should be provided with adequate social, economic, physical, and psychological support. PRACTICE IMPLICATION: Responsive strategies to support caregivers' should be taken as means of social, economic, physical, and psychological needs.