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Behçet's Syndrome (BS) is a chronic vasculitis of unknown etiology. Arterial involvement occurring in the pulmonary artery is associated with poor prognosis. It may cause pulmonary thrombus (PTE) and aneurysm (PAA) which may also lead to a rare complication, intracardiac thrombus. PAA and PTE can be complications of BS and are associated with high morbidity and mortality. A 30-year-old male patient had a fever of 38.4°C, recurrent oral-genital ulcers, shortness of breath, cough, and sputum. In this case report, medical history, clinical and laboratory examinations, radiography, echocardiography, and computer tomography imaging examinations were performed. PAA, PTE, intracardiac and left popliteal vein thrombosis, and infective endocarditis were present. The patient was diagnosed with BS according to the International Study Group criteria. Surgery was performed for intracardiac thrombus. Vegetation within the thrombus was demonstrated histopathologically. The patient's clinical condition and laboratory tests improved with intervention and medical treatments. The patient with BS, PAA, PTE, intracardiac thrombus, and infective endocarditis was successfully treated with pulmonary embolization, antibiotics, and systemic immunosuppression, despite its rarity, poor prognosis, and high morbidity and mortality rates.
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OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.
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Síndrome de Behçet , Úlceras Orais , Criança , Humanos , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Úlceras Orais/etiologia , Úlceras Orais/tratamento farmacológico , Estudos Transversais , Imunossupressores/uso terapêutico , Árvores de DecisõesRESUMO
Objectives: This study aimed to investigate the potential effect of the mevalonate kinase (MVK) gene polymorphisms on the pathogenesis and clinical findings in ankylosing spondylitis (AS) patients. Patients and methods: This cross-sectional study was conducted with 103 participants (63 males, 40 females) between January 2013 and January 2014. Of these, 51 (32 males, 19 females; mean age: 37.3±10.2 years; range, 19 to 60 years) were adult AS patients who met the 1984 Modified New York Criteria, and 52 (31 males, 21 females; mean age: 33.8±12 years; range, 19 to 60 years) were healthy volunteers with similar demographics. MVK gene analysis was performed using polymerase chain reaction sequencing by isolating deoxyribonucleic acids from peripheral blood samples. We determined serum immunoglobulin (Ig)D levels using radial immunodiffusion. We performed physical examinations on the AS patients. The Bath Ankylosing Spondylitis Disease Activity Index and the Bath Ankylosing Spondylitis Functional Index forms were filled and erythrocyte sedimentation rate, C-reactive protein, and IgD levels were recorded. Results: There was no statistically significant difference in the mean age between the groups (p=0.121). The frequency of symptomatic single nucleotide polymorphisms (SNPs), c.769-38 C>T heterozygous, c.769-7 T>G heterozygous, and c.769-38 C>T homozygous were similar between the groups (15/15; p=0.646). Nonsymptomatic SNPs were more common in the patient group, but the difference was not significant (83/58; p>0.05). The rate of having an MVK gene polymorphism was 36 (70.6%) in the AS compared to the 33 (63.4%) in the control group (p>0.05). There were no associations in clinical findings between the AS patients with or without MVK gene polymorphisms. New heterozygous SNPs, I56V A>G, E281D G>D, V80I G>A, and C173Y G>A, were present in four AS patients. Conclusion: The frequency of MVK gene polymorphisms was higher in AS patients than in healthy controls. But there was no statistically significant difference. We determined no effect of the present polymorphisms on AS clinical and laboratory findings.
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Background/aim: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly small joints, such as hand and foot joints symmetrically with irreversible joint destruction. In this study, the relationship between CD39 expression and the treatment response of RA patients was examined to investigate its potential as a biomarker that demonstrates treatment response. Materials and methods: This study included 77 RA patients and 40 healthy controls (HC). The RA patients were divided into 2 groups based on their response to RA treatment, those with a good response to methotrexate (MTX) monotherapy and those with an inadequate response based on the American College of Rheumatology and the European League Against Rheumatism response criteria. Various immunological parameters and Disease Activity Score in 28 Joints (DAS28) were examined between the groups using the Student's t-test. Results: The monocytic myeloid-derived suppressor cell (M-MDSC) percentage was higher in the RA patient group versus the HC group. The CD39 expression in the T lymphocytes were higher in patients that responded well to the MTX compared to those showing inadequate response. Additionally, s negative correlation was found between the DAS28 and CD39 in the T cells. Conclusion: The results showed that the improvement in treatment response to the therapy in RA patients could be because of the enhancement in the CD39/adenosine (ADO) pathway. Therefore, therapies targeting the CD39/ADO pathway in T cells may improve RA treatments.
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Antirreumáticos , Apirase , Artrite Reumatoide , Metotrexato , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Metotrexato/uso terapêutico , Feminino , Masculino , Apirase/metabolismo , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Antirreumáticos/farmacologia , Adulto , Biomarcadores/sangue , Resultado do Tratamento , Antígenos CD/metabolismo , Estudos de Casos e Controles , Idoso , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
OBJECTIVES: Behçet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behçet's disease. METHODS: A total of 1762 male and 1216 female patients with Behçet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behçet's disease was calculated and compared between male and female patients. RESULTS: Genetic association analysis comparing male to female patients with Behçet's disease from Turkey revealed an association with male sex in HLA-B/MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 × 10-8). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behçet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behçet's disease was observed in male patients in HLA-B/MICA (rs116799036, OR = 1.45, P = 1.95 × 10-8), HLA-C (rs12525170, OR = 1.46, P = 5.66 × 10-7), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients. CONCLUSIONS: Male patients with Behçet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behçet's disease.
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Síndrome de Behçet , Humanos , Feminino , Masculino , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/epidemiologia , Síndrome de Behçet/genética , Estudo de Associação Genômica Ampla , Fatores de Risco , Antígenos HLA-C , Testes GenéticosRESUMO
INTRODUCTION: Systemic sclerosis (SSc) is a multisystemic disease. Thyroid involvement in systemic sclerosis is an overlooked issue. Our study aimed to evaluate the decreased thyroid volume in SSc. Also, we aimed to show the relationship between patients' thyroid volume and clinical and laboratory parameters. METHOD: This was a single-center, cross-sectional study. Eighty-six patients were included in the study. A radiologist evaluated patients' thyroid volumes by ultrasonography. Demographic and clinical characteristics of the patients were recorded. Skin thickness was evaluated by the modified Rodnan skin score (mRSS) and the disease severity by the Medsger severity score (MSS). Findings were analyzed statistically. RESULTS: Thyroid volume was in the atrophic range in 53.5% of the patients. There was a significant negative correlation between thyroid volume and mRSS, MSS, and disease duration. Logistic regression analysis showed that mRSS and disease duration were risk factors for thyroid atrophy. CONCLUSIONS: Many studies point out that thyroid autoantibodies are a cause of thyroid dysfunction in patients with SSc. However, in most of these studies, thyroid volume was not evaluated. As a result of our study, we saw that the major cause of thyroid dysfunction in our SSc patients was thyroid atrophy. Also, we observed that thyroid atrophy was more common in patients with interstitial lung disease. We would like to draw attention to the fact that thyroid dysfunction and volume changes increase with the disease's duration and severity in systemic sclerosis.
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BACKGROUND: For patients with systemic sclerosis (SSc), hand involvement is an underrated clinical manifestation. Therefore, the aim of this study was to investigate the efficacy of a hand exercise program and to demonstrate its effect on hand function, quality of life, anxiety, and depression in patients with SSc. METHODS: This study was designed as a single blind, randomized controlled comparative study. Sixty-two female patients with SSc were randomized into an exercise group (n = 32) or a control group (n = 30). After some were lost to follow-up, 25 patients were analyzed in each group. In the exercise group, the 8-week intervention consisted of isometric hand exercises and self-administered stretching repeated 10 times/2 sets per day. All patients were assessed using the Hand Mobility in Scleroderma (HAMIS) test, the Duruoz Hand Index (DHI), grip strength, the 36-item short form, Health Assessment Questionnaire-Disability Index (HAQ-DI), Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) at baseline and then again 4 and 8 weeks later. Within-group comparisons over time were analyzed using the Friedman test. Post hoc analysis was performed using the Wilcoxon signed rank test. A multiple linear regression analysis was used to define the impact of exercise on clinical status. RESULTS: Of the 50 total patients, the median age and the median body mass index were 55.5 years and 25.9 kg/m2. The median disease duration was 10.0 years. Thirty-four patients (68.0%) were diffuse cutaneous systemic sclerosis (dcSSC), whereas 16 (32.0%) were limited cutaneous systemic sclerosis (lcSSc). The primary outcome of handgrip strength, as well as the HAMIS, DHI, HAQ-DI, and BDI, significantly improved over time (p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p = 0.005, respectively). The between-group comparison indicated significant improvement in DHI, handgrip strength, HAQ-DI, BAI, and BDI in the exercise group (p = 0.02, p = 0.013, p < 0.001, p = 0.015, and p = 0.036, respectively). In the multiple linear regression analysis, exercise was found to be the most efficient factor affecting the improvement in HAMIS, DHI, HAQ-DI, and grip strength. CONCLUSIONS: The 8-week intervention composed of isometric hand exercises and self-administered stretching provided a significant improvement in handgrip strength, general health, quality of life, and psychological status for patients with SSc.
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Qualidade de Vida , Escleroderma Sistêmico , Avaliação da Deficiência , Terapia por Exercício , Feminino , Mãos , Força da Mão , Humanos , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/terapia , Método Simples-CegoRESUMO
AIM: The aim of this study was to detect macrovascular findings in systemic sclerosis (SSc) by means of color Doppler ultrasonography (CDUS) and to evaluate the relationship between the laboratory and clinical findings in the setting of the disease. METHODS: This was a cross-sectional study. Eighty-eight patients were included in the study. CDUS examinations of the bilateral carotid, vertebral, and peripheral arteries were performed. The presence of macrovascular involvement was investigated and recorded, and its relationships with the clinical, laboratory, and cardiovascular risk factors were evaluated. RESULTS: An atheromatous plaque was found in 67.7% of the 1936 arteries examined by CDUS. Of these 1936 arteries, 37.4% demonstrated a narrowing of the intraluminal diameter. On the other hand, the carotid intima-media thickness (CIMT) was found to have increased in 55.7% of the patients. This increase was found to be statistically correlated with disease duration, the modified Rodnan Skin Thickness Score, and the Medsger Disease Activity Score. But no relation existed with the disease subtype, age, or cardiovascular risk factors. Arterial occlusion was detected in 10 patients. An association was found between the CIMT values and arterial occlusion. CONCLUSIONS: In this study, we examined the arteries by means of CDUS, and we detected structural alterations in the peripheral and carotid arteries. We witnessed that these macrovascular changes had a close association with certain features of SSc. We think there is a need for broader prospective studies in order to evaluate the contribution of these factors to the macrovascular changes stated in the article.
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Artérias Carótidas/diagnóstico por imagem , Microvasos/patologia , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/patologia , Túnica Média/diagnóstico por imagem , Túnica Média/patologia , Ultrassonografia Doppler em Cores/métodos , Adulto , Idoso , Artérias/patologia , Espessura Intima-Media Carotídea , Estudos Transversais , Feminino , Humanos , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico por imagemRESUMO
OBJECTIVE: Behçet's disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. This study was undertaken to investigate genetic associations with Behçet's disease in a diverse multiethnic population. METHODS: A total of 9,444 patients and controls from 7 different populations were included in this study. Genotyping was performed using an Infinium ImmunoArray-24 v.1.0 or v.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed. RESULTS: We identified 2 novel genetic susceptibility loci for Behçet's disease, including a risk locus in IFNGR1 (rs4896243) (odds ratio [OR] 1.25; P = 2.42 × 10-9 ) and within the intergenic region LNCAROD/DKK1 (rs1660760) (OR 0.78; P = 2.75 × 10-8 ). The risk variants in IFNGR1 significantly increased IFNGR1 messenger RNA expression in lipopolysaccharide-stimulated monocytes. In addition, our results replicated the association (P < 5 × 10-8 ) of 6 previously identified susceptibility loci in Behçet's disease: IL10, IL23R, IL12A-AS1, CCR3, ADO, and LACC1, reinforcing the notion that these loci are strong genetic factors in Behçet's disease shared across ancestries. We also identified >30 genetic susceptibility loci with a suggestive level of association (P < 5 × 10-5 ), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behçet's disease revealed their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated. CONCLUSION: We performed the largest genetic association study in Behçet's disease to date. Our findings reveal novel putative functional variants associated with the disease and replicate and extend the genetic associations in other loci across multiple ancestries.
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Síndrome de Behçet/genética , Monócitos/imunologia , Receptores de Interferon/genética , Síndrome de Behçet/imunologia , Estudos de Casos e Controles , Cromossomos Humanos Par 10/genética , DNA Intergênico/genética , Epigênese Genética , Feminino , Mutação com Ganho de Função , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Lipopolissacarídeos , Masculino , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , RNA Mensageiro/metabolismo , Receptores de Interferon/imunologia , Receptor de Interferon gamaRESUMO
Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 × 10-5) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.
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Predisposição Genética para Doença/genética , Arterite de Takayasu/genética , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Doenças Inflamatórias Intestinais/genética , Masculino , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
The aim of the present study was to examine the effects of age on mucocutaneous activity by using moderation analysis in Behçet's syndrome (BS). In this cross-sectional study, 887 BS patients (female : male, 481:406; mean age, 38.4 ± 10.9 years) followed in 13 tertiary centers in Turkey were included. Mucocutaneous activity was evaluated by using the Mucocutaneous Index (MI) according to sex and disease course. Moderation analysis was performed to test the effect of age on mucocutaneous activity. A moderator variable is a third variable and affects the relationship between independent and outcome variables. Age was chosen as a potential moderator variable (interaction effect), MI score as the outcome variable and sex as an independent variable in the analysis. The moderation analysis tested the effects of age in three steps: whole BS patient group, patients without systemic involvement and those with systemic involvement. The moderation model was only significant in BS patients with systemic involvement (P = 0.0351), and a significant relationship was observed between female sex and MI score (P = 0.0156). In addition, the interaction plot showed that female patients had increased MI scores compared with male patients, especially in the 28-year-old age group (P = 0.0067). Moreover, major organ involvement was newly diagnosed in the majority of these young female BS patients. Our results suggest that the relationship between sex and mucocutaneous activity was moderated by age in the systemic involvement group. Also, increased mucocutaneous activity may be associated with new major organ involvement in young female BS patients with systemic involvement.
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Síndrome de Behçet , Adulto , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/epidemiologia , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Turquia/epidemiologiaRESUMO
OBJECTIVE: The aim of this multi-center study was to assess predictive factors for work-day loss as an indirect cost element in Behçet's syndrome (BS). METHODS: In this cross-sectional, multi-center study, 834 BS patients (F/M: 441/393, age mean: 38.4 ± 10.9 years) were included. Data were collected by a questionnaire regarding treatment protocols, disease duration, smoking pattern, frequency of medical visits during the previous year and self-reported work-day loss during the previous year. RESULTS: Work-day loss was observed in 16.2% of patients (M/F: 103/32). The percentages of being a smoker (81.8%), using immunosuppressive (IS) medications (82%), and having disease duration <5 years (74%) were higher in male patients with work-day loss (P < .05). The majority of males (90.9%) had more than four clinic visits during the previous year. Moreover, the mean work-day loss (30.8 ± 57.7 days) was higher in patients with vascular involvement (56.1 ± 85.9) than those without (26.4 ± 50.6 days) (P = .046). In addition, increased frequency of ocular involvement (25.9%) was also observed in patients with work-day loss compared to others (8.6%) (P = .059). CONCLUSION: Work-day loss was associated with both vascular and ocular involvement. Close associations were observed among male gender, early period of the disease, frequent medical visits, being a smoker and treatment with IS medications in patients with work-day loss.
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Síndrome de Behçet/economia , Trabalho/estatística & dados numéricos , Adulto , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Custos e Análise de Custo , Estudos Transversais , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: The aim of this multicentre study was to understand patients' needs and to evaluate the oral ulcer activity with the Composite Index (CI), according to different treatment modalities in Behçet's syndrome (BS). METHODS: BS patients (n=834) from 12 centres participated in this cross-sectional study. Oral ulcer activity (active vs. inactive) and the CI (0: inactive vs. 1-10 points: active) were evaluated during the previous month. The effects of treatment protocols [non-immunosuppressive: non-IS vs. immunosuppressive: (ISs)], severity (mild vs. severe), disease duration (<5 years vs. ≥5 years) and smoking pattern (non-smoker vs. current smoker) were analysed for oral ulcer activity. RESULTS: Oral ulcer activity was observed in 65.1% of the group (n=543). In both genders, the activity was higher in mild disease course with non-IS treatment group compared to severe course with ISs (p<0.05). As a resistant group, patients with mild disease course whose mucocutaneous symptoms were unresponsive to non-IS medications were treated with ISs in a limited period and achieved the highest CI scores in females. Oral ulcer activity and poor CI score were associated with disease duration less than 5 years compared to others in male patients (p<0.05). CONCLUSIONS: Oral ulcer activity pattern is affected by both the combination of disease course, treatment protocols and disease duration. CI scores reflected the oral clinical activity and CI might be a candidate scale to evaluate the efficacy of treatments during the follow-up of oral ulcer activity in BS.
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Síndrome de Behçet , Imunossupressores/uso terapêutico , Úlceras Orais , Síndrome de Behçet/classificação , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Úlceras Orais/classificação , Recidiva , Índice de Gravidade de DoençaRESUMO
Background/aim: Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation. The study aimed to assess serum 14-3-3eta, anti-CarP, and anti-Sa in seronegative RA (SNRA) patients who were treatment-naïve as well as in healthy subjects. This is the first study in the literature to examine these autoantibodies together in SNRA patients. Materials and methods: Forty-five treatment-naïve SNRA patients and 45 healthy subjects were recruited. Drugs change the levels of autoantibodies; therefore, patients who took any medication had been excluded from our study. Anti-carbamylated protein, anti-Sa, and 14-3-3eta were measured by using three different ELISA kits. Results: Median serum concentration of healthy controls in 14-3-3eta was 0.02 (0.020.27) ng/mL. Median serum concentration of SNRA patients in 14-3-3eta was 1.00 (0.481.28) ng/mL. Data were analyzed with MannWhitney U tests; the P-value was <0.001 in 14-3-3eta. Receiver operating characteristic (ROC) curve analysis showed that 14-3-3eta in SNR compared to healthy controls had a significant (P < 0.001) area under the curve (AUC) of 0.90 (95% confidence interval, 0.830.96). At a cutoff of ≥0.33 ng/mL, the ROC curve yielded a sensitivity of 88.9%, a specificity of 82.2%, a positive predictive value of 83.3%, and a negative predictive value of 88.1%. Conclusion: We found that 14-3-3eta can be used as a diagnostic marker in SNRA.
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Proteínas 14-3-3/sangue , Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/sangue , Autoanticorpos/sangue , Carbamatos/imunologia , Vimentina/imunologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes SorológicosRESUMO
INTRODUCTION: Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), a subgroup of obsessive-compulsive disorder (OCD), has received much attention even though the specific underlying mechanisms remain unknown. Mannose-binding lectin (MBL) is a key factor in the innate immune response. The aim of this study was to investigate the role of MBL2 gene polymorphisms in pediatric OCD patients diagnosed as PANDAS, PANDAS-Variant and non-PANDAS. METHODS: The study included 102 pediatric OCD patients (59 [57.8% ] PANDAS, 20 [19.6% ] non-PANDAS, and 23 [22.5% ] PANDAS-Variant) and 60 healthy controls. Polymorphisms at codon 52, 54 and 57 of the MBL2 gene were investigated. RESULTS: Codon 54 polymorphism and any variant of MBL2 gene were significantly more frequent in the OCD group than in the control group (OR=2.97, 95% CI: 1.26-6.97; and OR=2.66, 95% CI: 1.32-5.38, respectively). According to regression analysis, the presence of any variant of MBL2 gene was found in 14.50-fold increased frequency in the PANDAS subgroup compared with the non-PANDAS subgroup (95% CI: 2.49-84.19). CONCLUSIONS: Our findings support an association between MBL2 genotypes and pediatric OCD, particularly PANDAS-OCD.
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Background/aim: The distribution of Mediterranean fever (MEFV) gene mutations in Turkish familial Mediterranean fever (FMF) patients varies according to geographic area of Turkey. There is a need for highly representative data for Turkish FMF patients. The aim of our study was to investigate the distribution of the common MEFV mutations in Turkish FMF patients in a nationwide, multicenter study. Materials and methods: Data of the 2246 FMF patients, from 15 adult rheumatology clinics located in different parts of the country, were evaluated retrospectively. The following mutations have been tested in all patients: M694V, M680I, M694I, V726A, and E148Q. Results: There were 1719 FMF patients with available genetic testing. According to the genotyping, homozygous M694V, present in 413 patients (24%), was the most common mutation . One hundred and fifty-four (9%) of patients had no detectable mutations. Allele frequencies of common mutations were: M694V (n = 1529, 44.5%), M680I (n = 423, 12.3%), V726A (n = 315, 9.2%), E148Q (n = 214, 1%), and M694I (n = 12, <1%). Conclusion: In this large-scale multicenter study, we provided information about the frequencies of common MEFV gene mutations obtained from adult Turkish FMF patients. Nearly half of the patients were carrying at least one M694V mutations in their alleles.
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Proteínas do Citoesqueleto/genética , Febre Familiar do Mediterrâneo/genética , Genética Populacional , Mutação/genética , Pirina/genética , Adolescente , Adulto , Criança , Análise Mutacional de DNA , Febre Familiar do Mediterrâneo/diagnóstico , Feminino , Frequência do Gene , Predisposição Genética para Doença/epidemiologia , Testes Genéticos , Genética Populacional/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Estudos Retrospectivos , Turquia/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. Most of the identified disease-causing mutations are located on exon 10. As the number of studies about the effect of the exonal location of the mutation and its phenotypic expression is limited, we aimed to investigate whether the exonic location of the Mediterranean fever (MEFV) mutation has an effect on the clinical manifestation in patients with FMF. METHODS: Study population was derived from the main FMF registry that included 2246 patients from 15 different rheumatology clinics. We categorized the mutations according to their exon locations and retrieved the clinical and demographic information from the database. RESULTS: Patients having the MEFV mutations on exon 2 or 10 (n:1526) were divided into three subgroups according to the location of the MEFV mutations: Group 1 (exon 2 mutations), Group 2 (exon 10 mutations), and Group 3 (both exon 2 and exon 10 mutations). Group 2 patients were of a significantly younger age at onset, and erysipel-like erythema, arthritis, amyloidosis, and a family history of FMF were more common in this group. CONCLUSION: Patients with FMF and exon 10 mutations show more severe clinical symptoms and outcome. Exon 2 mutations tend to have a better outcome.
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BACKGROUND: Impaired systolic function is common in sarcoidosis however the frequency of diastolic dysfunction (DD) and it's possible genetic basis has not been fully elucidated yet. The aim of this study is to evaluate the frequency of left ventricular DD(LVDD) and right ventricular DD(RVDD) and it's possible relationship between Human Leukocyte Antigen(HLA)-DRB1* alleles in patients with sarcoidosis. METHODS: Seventy seven patients (51 females, mean age 41.1±8.2yrs) without known sarcoid related or any other structured heart disease and 77 healthy controls with a similar age and gender (38.7±7.8yrs,51 females) were included in the case control study. DD was diagnosed with echocardiography. RVDD was defined as early(E)/late(A) ratio<1 or >2 on tricuspit valve. LVDD was defined as E/A ratio<1 or >2 on mitral valve, with isovolumetric relaxation time(IVRT)>90 miliseconds(msn) or deceleration rate of early diastolic flow(Edec)>220msn respectively. All patients were HLAtyped with the Sequence Specific Oligonucleotide Probe(SSOP) method. RESULTS: The frequencies of LVDDs and RVDDs were significantly higher in sarcoidosis patients than the controls (26.0% vs. 2.6% for LVDD; and 42.9% vs. 18.2% for RVDD)(p<0.05). No significant difference was found in patients according to the presence of RVDD and LVDD in terms of age, gender or respiratory function test parameters. Although the frequency of HLA DRB1* alleles were comparable among patients with RVDD, HLA DRB1*14 alleles were more frequent in patients with LVDD. CONCLUSIONS: Biventricular DD is common in patients with sarcoidosis without manifest cardiac involvement. HLA DRB1*14 allele seems to be related with LVDD in this study population.
Assuntos
Cadeias HLA-DRB1/genética , Sarcoidose Pulmonar/complicações , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Direita/etiologia , Função Ventricular Esquerda/genética , Função Ventricular Direita/genética , Adulto , Estudos de Casos e Controles , Diástole , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/genética , Sarcoidose Pulmonar/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/genética , Disfunção Ventricular Direita/fisiopatologiaRESUMO
Pain is one of the most common symptoms in systemic sclerosis (SSc) patients, yet not considered in the assessment of disease severity. This study aimed to investigate the frequency of neuropathic pain (NP) and to evaluate its interference with the quality of life (QoL) in SSc patients. Diffuse and Limited SSc patients diagnosed by American College of Rheumatology 2013 criteria were included in the study. Pain was evaluated with Visual Analogue Scale (VAS); presence of NP was screened with The Leeds Assessment of Neuropathic Symptoms and Signs (LANNS) questionnaire; disease activity was evaluated with modified Medsger Severity Scale (MSS) and QoL with short-form 36 (SF-36). One hundred twenty patients were included in the study (mean age 53.64 ± 11.44 years, female/male 83.3-16.7%). Total pain frequency was found 69.2% and NP was 35.9% in the entire patient group. Pain was most frequently seen in wrist-hand (50.6%) and ankle-foot (43.4%) regions; albeit, NP rates were highest in face (94.4%), lower leg (87.5%), and hip-thigh (78.6%) regions. SF-36 scores were significantly lower in patients with NP than the patients without NP (P < 0.05). The most associated factors with NP were MSS score for muscle involvement and drug consumption of the patient. According to our results, high frequency of NP is seen in SSc patients, and NP is associated with low QoL. Differential diagnosis of NP is important to consider right treatment options and accurate management of pain in all rheumatologic diseases including SSc.