scholarly journals A unique circulating miRNA profile highlights thrombo-inflammation in Behçet’s syndrome

2021 ◽  
pp. annrheumdis-2021-220859
Author(s):  
Giacomo Emmi ◽  
Giacomo Bagni ◽  
Elena Lastraioli ◽  
Francesca Di Patti ◽  
Alessandra Bettiol ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Validation Cohort ◽  
Systemic Vasculitis ◽  
Mirna Profile ◽  
Inactive Disease ◽  
Pcr Analysis ◽  
Behçet’S Syndrome ◽  
Behçet's Syndrome ◽  
Behcet’S Syndrome ◽  
Behcet's Syndrome

ObjectivesBehçet’s syndrome (BS) is a rare systemic vasculitis often complicated by thrombotic events. Given the lack of validated biomarkers, BS diagnosis relies on clinical criteria.In search of novel biomarkers for BS diagnosis, we determined the profile of plasmatic circulating microRNAs (ci-miRNAs) in patients with BS compared with healthy controls (HCs).Methodsci-miRNA profile was evaluated by microarray in a screening cohort (16 patients with BS and 18 HCs) and then validated by poly(T) adaptor PCR (PTA-PCR) in a validation cohort (30 patients with BS and 30 HCs). Two disease control groups (30 patients with systemic lupus erythematosus (SLE) and 30 patients with giant cell arteritis (GCA) were also analysed.ResultsFrom the microarray screening, 29 deregulated (differentially expressed (DE)) human ci-miRNAs emerged. A hierarchical cluster analysis indicated that DE ci-miRNAs clearly segregated patients from controls, independently of clinical features. PTA-PCR analysis on the validation cohort confirmed the deregulation of miR-224-5p, miR-206 and miR-653-5p. The combined receiver operating characteristic (ROC) curve analyses showed that such ci-miRNAs discriminate BS from HCs (and BS with active vs inactive disease), as well as BS from patients with SLE and GCA.The functional annotation analyses (FAAs) showed that the most enriched pathways affected by DE ci-miRNAs (ie, cell–matrix interaction, oxidative stress and blood coagulation) are related to thrombo-inflammatory mechanisms. Accordingly, the expression of the three ci-miRNAs from the validation cohort significantly correlated with leucocyte reactive oxygen species production and plasma lipid peroxidation.ConclusionsThe ci-miRNA profile identified in this study may represent a novel, poorly invasive BS biomarker, while suggesting an epigenetic control of BS-related thrombo-inflammation.

scholarly journals Neutrophil-mediated mechanisms in non-vascular Behçet’s syndrome

2021 ◽  
Author(s):  
Alessandra Bettiol ◽  
MATTEO BECATTI ◽  
Elena Slvestri ◽  
Flavia Rita Argento ◽  
Eleonora Fini ◽  
...  
Keyword(s):  
Systemic Vasculitis ◽  
Clinical Manifestations ◽  
Gastrointestinal Symptoms ◽  
Inactive Disease ◽  
Behçet’S Syndrome ◽  
Ros Production ◽  
Behçet's Syndrome ◽  
Intracellular Ros ◽  
Behcet’S Syndrome ◽  
Behcet's Syndrome

Objective: Behçet’s syndrome (BS) is a systemic vasculitis with several clinical manifestations. Neutrophils hyperactivation mediates vascular BS involvement, via a massive production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). We investigated neutrophil-mediated mechanisms of damage in non-vascular BS manifestations and explored in vitro the effects of colchicine in counteracting these mechanisms. Methods: NETs and intracellular ROS production was assessed in blood samples from 80 BS patients (46 with active non-vascular BS, 34 with inactive disease) and 80 healthy controls. Moreover, isolated neutrophils were incubated for 1 hour with an oxidating agent (2,2′-azobis (2-amidinopropane) dihydrochloride; 250nM), and the ability of pure colchicine pre-treatment (100ng/ml) to counteract oxidation-induced damage was assessed. Results: Patients with active non-vascular BS had remarkably increased NET levels [21.2 (IQR 18.3-25.9) mU/ml] compared to patients with inactive disease [16.8 (13.3-20.2) mU/ml] and to controls [7.1 (5.1-8.7) mU/ml], p<0.001]. Also, intracellular ROS tended to be increased in active BS, although not significantly. In active non-vascular BS, NETs correlated with neutrophils ROS production (p<0.001) and were particularly increased in patients with active mucosal (p<0.001), articular (p=0.004), and gastrointestinal symptoms (p=0.006). On isolated neutrophils, colchicine significantly reduced oxidation-induced NET production and cell apoptosis, though not via an antioxidant activity. Conclusion: Neutrophil-mediated mechanisms might be directly involved in non-vascular BS, and NETs, more than ROS, might drive the pathogenesis of mucosal, articular and intestinal manifestations. Colchicine might be effective to counteract neutrophils-mediated damage in BS, although further studies are needed.

scholarly journals Discordance between patient and physician global assessment of disease activity in Behçet’s syndrome: a multicenter study cohort

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Alberto Floris ◽  
◽  
Gerard Espinosa ◽  
Luisa Serpa Pinto ◽  
Nikolaos Kougkas ◽  
...  
Keyword(s):  
Disease Activity ◽  
Global Assessment ◽  
Inactive Disease ◽  
Ocular Involvement ◽  
Behçet’S Syndrome ◽  
Behçet's Syndrome ◽  
Patient Reported ◽  
Behcet’S Syndrome ◽  
Assessment Of Disease Activity ◽  
Behcet's Syndrome

Abstract Background To compare the patients’ and physician’s global assessment of disease activity in Behçet’s syndrome (BS) and investigate the frequency, magnitude, and determinants of potential discordance. Methods A total of 226 adult BS patients with a median (IQR) age of 46.9 (35.6–55.2) years were enrolled across Italy, Greece, Portugal, and Spain. Demographic, clinical, and therapeutic variables, as well as the patient reported outcomes, were collected at the recruitment visit. The physical (PCS) and mental (MCS) component summary scores of the Short Form Questionnaire 36 (SF-36) and the Behçet’s syndrome Overall Damage Index (BODI) were calculated. Disease activity was assessed by the patients’ (PtGA) and physician’s global assessment (PGA) in a 10-cm visual analog scale, as well as the Behçet Disease Current Activity Form (BDCAF). Discordance (∆) was calculated by subtracting the PGA from the PtGA and defined as positive (PtGA>PGA) and negative (PtGA<PGA) discordance using both a more stringent (∆ = ±2) and a less stringent (∆ = ±1) cutoff. Univariate and multivariate logistic regressions were performed. Results Median PtGA and PGA scores were 2.0 (0.3–5.0) and 1.0 (0.0–3.0) cm, respectively. The discordance prevalence varied (from 29.6 to 55.3%) according to the cutoff applied, and the majority (> 80%) of disagreements were due to patients rating higher their disease activity. Higher values of BDCAF were associated to increased rate of positive discordance. When BDCAF = 0, the median (IQR) values of PtGA and PGA were 0.2 (0–2) and 0 (0–1), respectively. PCS (adjusted odds ratio (adjOR) 0.96 per unit, 95% CI 0.93–0.98, p = 0.006) and MCS (adjOR 0.96 per unit, 95% CI 0.93–0.99, p = 0.003) were independently associated with positive discordance using both cutoffs. Active ocular involvement emerged as a potential determinant of negative discordance (adjOR 5.88, 95% CI 1.48–23.30, p = 0.012). Conclusions PtGA and PGA should be considered as complementary measures in BS, as patients and physicians may be influenced by different factors when assessing active disease manifestations. Particularly, PtGA may be a useful tool in the assessment of BS disease activity, as it carries a low risk to misclassify an inactive disease, and may allow to capture aspects of the patient’s health that negatively affect his well-being and the treatment.

scholarly journals Pathogenesis of Behçet's Syndrome: Genetic, Environmental and Immunological Factors

2021 ◽  
Vol 8 ◽  
Author(s):  
Irene Mattioli ◽  
Alessandra Bettiol ◽  
Güher Saruhan-Direskeneli ◽  
Haner Direskeneli ◽  
Giacomo Emmi
Keyword(s):  
Systemic Vasculitis ◽  
Strong Association ◽  
Current Evidence ◽  
Behçet’S Syndrome ◽  
Predisposing Factor ◽  
Behçet's Syndrome ◽  
Wide Range ◽  
Behcet’S Syndrome ◽  
Immunological Factors ◽  
Behcet's Syndrome

Behçet's syndrome (BS) is a rare systemic vasculitis, characterized by a wide range of different clinical involvements and unpredictable phases of recurrence and remission. BS can be described as a multifactorial disease with an incompletely known etiopathogenesis; in fact, though presenting some peculiar features, such as its typical geographic distribution and the strong association with the well-known genetic predisposing factor HLA-B*51, the cause behind the onset and progression of the disease remains currently not fully understood. Besides genetic HLA and non-HLA predisposing associations and epigenetic influence, environmental factors also play an important role in the pathogenesis of the disease, and among these, infectious agents (both bacterial and viral) and specific microbiome alterations are considered of particular relevance in BS pathogenesis. BS has been included for decades among autoimmune diseases, in light of evidence showing T- and B-cell aberrant responses. However, because of recurrent mucocutaneous lesions and episodes of inflammation without antigen-specific T-cell or autoantibody responses, BS has also been classified among autoinflammatory disorders. Nevertheless, differently from autoinflammatory diseases, BS mildly responds to therapies targeting IL-1, its onset is not usually in childhood, and has high neutrophilic vasculitic involvement. Finally, given the association with HLA class I alleles, similar to spondyloarthropathies, the concept of BS as a major histocompatibility complex (MHC) I -opathy has been introduced. Understanding the complex etiopathogenesis of BS is essential to identify modifiable risk factors of BS occurrence or exacerbation and to develop targeted therapies. This review summarizes current evidence on the main genetic, environmental and immunological factors contributing to BS development.

Behçet: the syndrome

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_3) ◽  
pp. iii101-iii107 ◽  
Author(s):  
Alessandra Bettiol ◽  
Domenico Prisco ◽  
Giacomo Emmi
Keyword(s):  
Systemic Vasculitis ◽  
Current Evidence ◽  
Patient Specific ◽  
Behçet’S Syndrome ◽  
Behçet's Syndrome ◽  
Disease Phenotypes ◽  
Genetic Features ◽  
Distinct Disease ◽  
Behcet’S Syndrome ◽  
Behcet's Syndrome

Abstract Behçet’s syndrome (BS) is a systemic vasculitis characterized by a relapsing and remitting course. It can involve the skin, mucosa, joints, vessels (arteries and/or veins), eyes, and nervous and gastrointestinal systems, and so is referred to as a syndrome rather than as a unique and nosologically distinct condition. These involvements may present alone or co-exist in the same patient. Although all the possible combinations of the above-mentioned manifestations may occur, clusters of commonly co-existing involvements (also referred to as ‘disease phenotypes’) have been suggested, namely ‘mucocutaneous and articular’, ‘peripheral vascular and extra-parenchymal neurological’ and ‘parenchymal neurological and ocular’ phenotypes have been described. Patient-specific demographic and genetic features have been described as positively or negatively associated with specific disease phenotypes. This review will focus on the different clinical features of Behçet’s syndrome, summarizing current evidence on the distinct disease manifestations as well as the major phenotypes.

Clinical and epidemiological features of visual organ damage in systemic connective tissue diseases

2020 ◽  
Vol 1-2 (211-212) ◽  
pp. 67-74
Author(s):  
Akmarzhan Rystanbayeva ◽  
◽  
Aigul Balmukhanova ◽  
Olga Mashkunova ◽  
Kuralay Kaynazarova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Connective Tissue ◽  
Systemic Vasculitis ◽  
Connective Tissue Diseases ◽  
Clinical Manifestations ◽  
Posterior Uveitis ◽  
Behçet’S Syndrome ◽  
Behçet's Syndrome ◽  
Behcet’S Syndrome ◽  
Behcet's Syndrome

To this date, uveitis associated with connective tissue diseases remain relevant due to serious complications that significantly reduce vision and thus worsen the quality of life of patients. Aim. To study the frequency and prevalence, as well as clinical manifestations of ophthalmopathology in connective tissue diseases. Material and methods. A retrospective and prospective study of 534 patients (144 men and 390 women) with connective tissue diseases was conducted, in which ophthalmological disorders were detected. The patients underwent standard rheumatological examination in the department. And also, ophthalmological examination with the determination of visual acuity, intraocular pressure and the use of biomicroscopy, ophthalmoscopy (or cycloscopy). If necessary and possible, additional studies were performed such as: ultrasound B-scan, optical coherence tomography, perimetry. The study examined the type of common disease, age of onset and gender of the patient. Of particular interest were patients with uveal inflammation, in which the localization and nature of the course of inflammation were evaluated. Results and discussion. The most common diseases with eye damage were rheumatoid arthritis (RA) – 129 (24.1%), systemic lupus erythematosus (SLE) – 92 (17.2%), inflammatory bowel disease (IBD) – 95 (17.8%), systemic scleroderma (SDS) – 54 (10.1%) and spondylarthritis (Spa) – 41 (7.8%). In a small percentage of cases, other connective tissue diseases were diagnosed, such as: mixed connective tissue diseases (MCTS) – 24 (4.5%), Overlap syndrome – 21 (3.9%), systemic vasculitis – 23 (4.3%), Behcet's syndrome -18 (3.4%), Sjogren disease – 14 (2.6%) and juvenile idiopathic arthritis - 7 (1.3%). All ophthalmic disorders were divided into four general groups and distributed as follows: inflammatory 27.7%, degenerative 4.9%, vascular 48.7%, side effects of glucocorticoids 18.7%. Uveitis accounted for 52 (9.7%) of all ophthalmopathology, occurring in connective tissue diseases. Unilateral acute anterior uveitis (AAU) was diagnosed in 13 (25%) patients with ankylosing spondylitis, of which 4 (7.8%) had a relapse in the paired eye. Simultaneously, bilateral AAU was detected in 3 (5.7%) patients with Behcet's syndrome. Chronic, recurrent posterior uveitis was diagnosed in 13 (25%) patients with Behcet's systemic vasculitis. All patients with Behcet's syndrome were male at the age of 31±3.1 years. The uveal process approximately started 3.2±1.16 years after the onset of systemic disease. Generalization of inflammation in all departments of uvea was detected in patients with PSA-5 (9.6%), AC – 3 (5.7%), DS – 2 (3.8%) and SLE – 2 (3.8%). In 5 (9.6%) patients, the process was bilateral. Inflammation of the paired eye by the type of AAU was observed in 1 patient and posterior uveitis - in 2 patients. Conclusions. Ophthalmic disorders in the structure of systemic diseases make up 20.2% and vary widely in their clinical manifestations. Chronic blepharoconjunctivitis, combined with rheumatoid arthritis (46%) is a common inflammation of the accessory structures of the eye. About 20% of patients have complications from general immunosuppressive therapy, leading to impaired visual function. The frequency of uveitis in the structure of ophthalmopathology associated with connective tissue disease is 9.7%. Uveitis associated with ankylosing spondylitis and systemic vasculitis of Behcet occurs in men at a younger age and is 31%. More than half (63%) of patients with uveitis have a severe course with the development of panuveitis and neuropathy. An increase in the thickness of the choroid (up to 2 mm) according to two-dimensional ultrasound is an early diagnostic criterion for the development of uveitis and the underlying disease of connective tissue. Keywords: inflammatory eye diseases, uveitis, connective tissue diseases, spondyloarthritis, Behcet's syndrome, complications.

scholarly journals Clinical Manifestations and Diagnosis of Behçet’s Syndrome

2021 ◽  
pp. 94-104
Author(s):  
Sara Beça ◽  
Gerard Espinosa
Keyword(s):  
Systemic Vasculitis ◽  
Clinical Manifestations ◽  
Disease Assessment ◽  
Significant Heterogeneity ◽  
Behçet’S Syndrome ◽  
Behçet's Syndrome ◽  
Clinical Presentations ◽  
Wide Range ◽  
Behcet’S Syndrome ◽  
Behcet's Syndrome

Behçet’s syndrome (BS) is a systemic vasculitis with a wide range of clinical presentations and disease courses. It may involve the mucosa, skin, joints, vessels, eyes, and nervous and gastrointestinal systems. These organ involvements may present alone or co-exist in the same patient. Three main clusters of commonly co-existing manifestations were recognised and are currently called disease phenotypes. There is a significant heterogeneity among patients regarding demographic features and clinical expression of the disease that hinders a standardised disease assessment and a generalised use of diagnostic criteria. Additionally, BS is not associated with pathognomonic laboratory or histopathology features; therefore, the diagnosis is mainly based on the clinical manifestations. The purpose of this narrative review of the literature is to provide a description of the most common or typical clinical features of BS, summarise the major phenotypes of BS, and address the diagnosis strategy of this syndrome.

Behcet's syndrome

1970 ◽  
Vol 102 (1) ◽  
pp. 116-117 ◽  
Author(s):  
J. L. Fromer
Keyword(s):  
Behçet’S Syndrome ◽  
Behçet's Syndrome ◽  
Behcet’S Syndrome ◽  
Behcet's Syndrome
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