Dysregulation of miRNA-30e-3p targeting IL-1β in an international cohort of systemic autoinflammatory disease patients

Abstract: Autoinflammation is the standard mechanism seen in systemic autoinflammatory disease (SAID) patients. This study aimed to investigate the effect of a candidate miRNA, miR-30e-3p, which was identified in our previous study, on the autoinflammation phenotype seen in SAID patients and to analyze its expression in a larger group of European SAID patients. We examined the potential anti-inflammatory effect of miR-30e-3p, which we had defined as one of the differentially expressed miRNAs in microarray analysis involved in inflammation-related pathways. This study validated our previous microarray results of miR-30e-3p in a cohort involving European SAID patients. We performed cell culture transfection assays for miR-30e-3p. Then, in transfected cells, we analyzed expression levels of pro-inflammatory genes; IL-1β, TNF-α, TGF-β, and MEFV. We also performed functional experiments, caspase-1 activation by fluorometric assay kit, apoptosis assay by flow cytometry, and cell migration assays by wound healing and filter system to understand the possible effect of miR-30e-3p on inflammation. Following these functional assays, 3'UTR luciferase activity assay and western blotting were carried out to identify the target gene of the aforementioned miRNA. MiR-30e-3p was decreased in severe European SAID patients like the Turkish patients. The functional assays associated with inflammation suggested that miR-30e-3p has an anti-inflammatory effect. 3'UTR luciferase activity assay demonstrated that miR-30e-3p directly binds to interleukin-1-beta (IL-1β), one of the critical molecules of inflammatory pathways, and reduces both RNA and protein levels of IL-1β. miR-30e-3p, which has been associated with IL-1β, a principal component of inflammation, might be of potential diagnostic and therapeutic value for SAIDs. Key Messages: miR-30e-3p, which targets IL-1β, could have a role in the pathogenesis of SAID patients.miR-30e-3p has a role in regulating inflammatory pathways like migration, caspase-1 activation.miR-30e-3p has the potential to be used for future diagnostic and therapeutic approaches.</p

A patient-driven registry on Behçet’s disease: the AIDA for patients pilot project

IntroductionThis paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet’s disease (BD).MethodsThe project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry.ResultsRespondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet’s Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0–30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1–50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range – 1.8–4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p &lt; 0.001), the presence of any major organ involvement (p &lt; 0.031), the presence of gastro-intestinal (p &lt; 0.001), neurological (p = 0.012) and musculoskeletal (p = 0.022) symptoms, recurrent fever (p = 0.002), and headache (p &lt; 0.001) were associated to a higher number of accesses to the healthcare system. Multiple linear regression showed that the BDQoL score could significantly predict the global socioeconomic impact of BD (F = 14.519, OR 1.162 [CI 0.557–1.766], p &lt; 0.001).DiscussionPreliminary results from the AIDA for Patients BD registry were consistent with data available in the literature, confirming that PROs and PREs could be easily provided by the patient remotely to integrate physician-driven registries with complementary and reliable information

Çocuklarda Vertigo Etiyolojisi, Çocukluk Çağı Benign Paroksismal Vertigosu ve Migren Ilişkisi

Vertigo in children has received much less attention in the literature than vertigo in adults and there is no standart algorithm for evaluation of these children. The most common reason of vertigo in childhood, benign paroxysmal vertigo of childhood (BPVC) is thought to be a migraine precursor. The aim of this study was to describe the characteristics of vertigo in pediatric patients presenting to a tertiary neurology clinic and to investigate the relationship between BPVC and migraine. All patients younger than 18 years of age and presenting with vertigo to Hacettepe University Ihsan Dogramaci Children?s Hospital Neurology Unit between January 1996-January 2012 were included in the study. These patients were retrospectively analysed through the patient files and follow-up data were obtained with phone interviews. One hundred patients with a mean age of 7,5 years were evaluated in our study. The most common symptoms associated with vertigo were headache (20%) and nausea (17%). The most common vertigo etiologies were BPVC (39%), psychogenic vertigo (21%), epileptic vertigo (15%), and migraine-associated vertigo (MAV) (11%). The most common etiology was BPVC in children ?5 years of age, while it was psychogenic vertigo in older children. Staring episodes were more common in epileptic vertigo patients (p=0,021) while headache was more commonly associated with MAV (p<0,001). Vertigo attacks lasting more than five minutes were less common in BPVC patients compared with others (p=0,013). Six (20%) out of 30 BPVC patients contacted through phone interviews were experiencing migraine type headaches. An algorithm for evaluation of children presenting with vertigo was formed based on data obtained from this study and the literature. When this algorithm was applied to 30 randomly selected cases from this series, 23 (76,6%) were correctly diagnosed. In most of the cases of vertigo disorders in children, a thorough medical history and a detailed physical examination, neurological examination and audiological evaluation are sufficient for accurate diagnosis. A standart algorithm for evalution of this patient group can help with the correct diagnosis and treatment.Çocukluk yaş grubunda vertigo, erişkin döneme göre daha az çalışılmış bir konu olup, vertigo yakınmasıyla başvuran çocukların değerlendirilmesinde belirli bir yaklaşım algoritması bulunmamaktadır. Çocuklarda vertigonun en sık nedeni bir migren öncülü olarak düşünülen çocukluk çağı benign paroksismal vertigosudur (ÇÇBPV). Bu çalışmanın amacı; üçüncü basamak bir hastanenin Pediatrik Nöroloji Ünitesi?ne vertigo yakınmasıyla başvuran çocuk hastaların özelliklerinin belirlenmesi ve ÇÇBPV ile migren ilişkisinin değerlendirilmesidir. Çalışmaya Hacettepe Üniversitesi İhsan Doğramacı Çocuk Hastanesi Nöroloji Polikliniği?ne, Ocak 1996-Ocak 2012 arasında vertigo yakınmasıyla başvuran 18 yaşından küçük tüm hastalar dahil edilmiştir. Bu hastaların bilgileri hasta dosyaları üzerinden geriye dönük olarak incelenmiş; son durumları telefon görüşmeleri ile öğrenilmiştir. Çalışmamızda, vertigo yakınmasının başlangıç yaşı ortalama 7,5 yaş olan 100 hasta değerlendirildi. Vertigoya en sık eşlik eden yakınmalar baş ağrısı (%20) ve mide bulantısıydı (%17). Klinikte en sık saptanan vertigo nedenleri ÇÇBPV (%39), psikojenik vertigo (%21), epileptik vertigo (%15) ve migrenle ilişkili vertigoydu (MİV) (%11). Beş yaş altı çocuklarda en sık vertigo nedeni ÇÇBPV iken, beş yaş üstü çocuklarda psikojenik vertigo ilk sırayı almaktaydı. Dalma-boş bakma yakınması epileptik vertigo hastalarında daha sıktı (p=0,021); baş ağrısı yakınmasının MİV hastalarında baş dönmesine daha sık eşlik ettiği görüldü (p<0,001). Beş dakikadan uzun süren vertigo atakları, ÇÇBPV hastalarında diğer hastalara göre daha az sıklıkta görülmekteydi (p=0,013). Telefonla ulaşılan 30 ÇÇBPV hastasının altısında (%20) migren tipi baş ağrısının olduğu öğrenildi. Çalışma sonuçları ve literatürden gelen bilgiler çerçevesinde vertigolu çocuğa yaklaşım şeması oluşturuldu. Bu şema, çalışma grubundan rastgele seçilen 30 hastaya uygulanarak denendiğinde, 23 (%76,6) hastaya doğru tanı konulabildiği görüldü. Vertigolu çocuk hastaların büyük kısmında ayrıntılı bir öykü ve nörolojik ve odyolojik değerlendirmeyi de içeren ayrıntılı bir muayene tanı konulması için yeterlidir. Bu grup hastaya yaklaşımda, standart bir yaklaşım protokolünün belirlenmesi, doğru tanı ve tedavi seçiminde yol gösterici olacaktır

Testing The Model For Predicting Effectiveness Of Anakinra In Systemic Juvenile Idiopathic Arthritis

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Familial Mediterranean Fever: Recent Developments In Pathogenesis And New Recommendations For Management

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.PubMedWoSScopu

Familial Mediterranean Fever: Current Perspectives

Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disease, and it is characterized by recurrent attacks of fever and polyserositis. The disease is associated with mutations in the MEFV gene encoding pyrin, which causes exaggerated inflammatory response through uncontrolled production of interleukin 1. The major long-term complication of FMF is amyloidosis. Colchicine remains the principle therapy, and the aim of treatment is to prevent acute attacks and the consequences of chronic inflammation. With the evolution in the concepts about the etiopathogenesis and genetics of the disease, we have understood that FMF is more complicated than an ordinary autosomal recessive monogenic disorder. Recently, recommendation sets have been generated for interpretation of genetic testing and genetic diagnosis of FMF. Here, we have reviewed the current perspectives in FMF in light of recent recommendations.PubMedScopu

A Proposed Treatment Scheme For Chronic Recurrent Multifocal Osteomyelitis (Crmo): A Case Series Of Nine Patients

PubMe

Vasculitis In Children

Primary systemic vasculitides of the young are relatively rare diseases, but are associated with significant morbidity and mortality, particularly if there is diagnostic delay. We provide an overview of paediatric vasculitides with emphasis on key differences in vasculitis presentation and management between children and adults. Significant advances in the field of paediatric vasculitis research include the development of classification criteria and disease outcome tools for paediatric disease; inclusion of paediatric patients in international multicentre randomized controlled trials of therapies in vasculitis; and development of rare disease trial designs for therapeutic trials of paediatric vasculitis. The continuation of unmet needs as well as the exploration of potential therapeutic avenues and considerations in the design of future trials are also discussed.WoSScopu