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1.
Am J Hum Genet ; 108(1): 84-99, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33308445

RESUMO

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.


Assuntos
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/genética
2.
Clin Exp Rheumatol ; 41(10): 2078-2086, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37902270

RESUMO

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.


Assuntos
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 Decisões
3.
Turk J Med Sci ; 53(5): 1075-1083, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38813034

RESUMO

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.


Assuntos
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/metabolismo
4.
J Autoimmun ; 132: 102882, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35987173

RESUMO

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.


Assuntos
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 Genéticos
5.
J Clin Rheumatol ; 28(2): e422-e429, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34030163

RESUMO

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.


Assuntos
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-Cego
6.
Clin Exp Rheumatol ; 37 Suppl 121(6): 98-104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31856935

RESUMO

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.


Assuntos
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 Doença
7.
Turk J Med Sci ; 49(5): 1498-1502, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651120

RESUMO

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.


Assuntos
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 Sorológicos
8.
Turk J Med Sci ; 49(2): 472-477, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30887796

RESUMO

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.


Assuntos
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 Jovem
9.
Rheumatol Int ; 38(1): 51-58, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29051974

RESUMO

Familial Mediterranean fever (FMF) is an autoinflammatory disease manifested by inflammatory attacks of peritonitis, pleuritis, pericarditis accompanied by fever and arthritis. Mutations of MEFV gene results in pyrin dysfunction, which causes uncontrolled interleukin-1 beta production and triggers the inflammatory attacks. Inflammation persists even during attack-free periods in one-third of the FMF patients. Findings of elevated proinflammatory cytokine patterns during remission as well as inflammatory attacks indicate the continuous subclinical disease activity and inflammation. Chronic inflammation was thought to be related to the cardiovascular risk in FMF patients. Main cardiac manifestations reported in FMF are pericarditis, idiopathic recurrent pericarditis, pericardiac tamponade, coronary heart disease and abnormal cardiovascular reactivity. Cardiac involvement in FMF may often be related to secondary AA amyloidosis. Deposition of amyloid may lead to cardiovascular morbidity and mortality in FMF patients. Associations of several vasculitic disorders such as Immunoglobulin A-associated vasculitis, polyarteritis nodosa and Behcet's disease are common in FMF. Appropriate prophylactic treatment with colchicine is recommended to prevent from cardiovascular risks. For those resistant to colchicine, IL-1 inhibitor agents can be used. Associated vasculitis should be treated with immunosuppressive agents. This review article aims to compile information about cardiac disease in FMF and refer to recent studies on the topic.


Assuntos
Amiloidose/etiologia , Doenças Cardiovasculares/etiologia , Febre Familiar do Mediterrâneo/complicações , Colchicina/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Genótipo , Humanos , Imunossupressores/uso terapêutico , Inflamação/etiologia , Fenótipo , Moduladores de Tubulina/uso terapêutico , Vasculite/tratamento farmacológico , Vasculite/etiologia
10.
Clin Exp Rheumatol ; 35 Suppl 103(1): 77-82, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27908308

RESUMO

OBJECTIVES: We aimed to assess the outcome of a large Takayasu arteritis (TAK) cohort using the vasculitis damage index (VDI) and quality of life (QoL) scale, tools which have been validated for vasculitis. METHODS: Disease activity, damage and QoL were cross-sectionally evaluated in 165 TAK patients from 6 centres. SF-36 were applied to 51 age-matched healthy controls (HC). Persistent activity for ≥6 months was considered as treatment resistance (r-TAK). The correlation between VDI, clinical characteristics and mental (MCS)/physical (PCS) component scores of SF-36 were analysed. SF-36 and VDI scores were compared between TAK subgroups and HC. RESULTS: The median age, follow-up time and disease duration were 40 (17-68), 60 (6-384), and 72 (6-396) months, respectively. 35% of them were r-TAK. VDI scores (VDIs) in TAK 4 (1-12) were mainly due to the disease itself [4 (1-10)]. VDIs in r-TAK were significantly higher than nr-TAK [5 (2-12) vs. 3 (2-10), p<0.001)]. In the TAK patients, MCS and PCS were found as 43±10 and 38±11, respectively. A high proportion of poor MCS (70%) and PCS (80%) were demonstrated in TAK. A significantly negative but weak correlation was observed between VDI and MCS (p=0.003, r=-0.23), PCS (p<0.001, r=-0.34). Higher VDIs were detected in patients with PCS <50 [5 (1-12) vs. 2 (1-6) p<0.001)]. SF-36 score was significantly lower in TAK than HC. CONCLUSIONS: Disease-related damage mainly caused by peripheral vascular involvement was more predominant than treatment-related damage without reaching the level of severe damage scores, but contributing to poor QoL, in the TAK cohort.


Assuntos
Qualidade de Vida , Arterite de Takayasu/patologia , Arterite de Takayasu/psicologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Estudos Transversais , Ciclofosfamida/uso terapêutico , Progressão da Doença , Resistência a Medicamentos , Feminino , Glucocorticoides/uso terapêutico , Nível de Saúde , Humanos , Imunossupressores/uso terapêutico , Masculino , Saúde Mental , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Arterite de Takayasu/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Turquia , Adulto Jovem
11.
Rheumatol Int ; 37(5): 675-684, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28289872

RESUMO

Patients with primary Sjogren's syndrome (pSS) may go undiagnosed or be misclassified due to the insidious nature and wide spectrum of the disease. The available several classification criteria emphasize glandular findings. We aimed to analyze the efficiency of various classification criteria sets in patients diagnosed on the clinical basis by expert opinion and to compare those pSS patients who fulfilled these criteria with those who did not. This is a multicenter study in which 834 patients from 22 university-based rheumatology clinics are included. Diagnosis of pSS was made on the clinical basis by the expert opinion. In this study, we only interviewed patients once and collected available data from the medical records. The European criteria, American-European Consensus Group (AECG) and American College of Rheumatology (ACR) Sjogren's criteria were applied. Majority of the patients were women (F/M was 20/1). The median duration from the first pSS-related symptom to diagnosis was significantly shorter in men (2.5 ± 2.3 vs 4.3 ± 5.9 years) (p = 0 < 0.016). When the European, AECG and ACR Sjogren's criteria were applied, 666 patients (79.9%) satisfied at least one of them. In total, 539 patients (64.4%) satisfied the European, 439 (52.6%) satisfied the AECG, and 359 (43%) satisfied the ACR criteria. Among the entire group, 250 patients (29.9%) satisfied all and 168 (20.1%) met none of the criteria. The rates of extraglandular organ involvements were not different between patients who met at least one of the criteria sets and those who met none. There is an urgent need for the modification of the pSS criteria sets to prevent exclusion of patients with extraglandular involvements as the dominant clinical features.


Assuntos
Síndrome de Sjogren/diagnóstico , Avaliação de Sintomas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reumatologia , Adulto Jovem
12.
J Autoimmun ; 69: 59-63, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26970681

RESUMO

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare condition, and treatment choices are frequently dependent on expert opinions. The objectives of the present study were to assess treatment modalities, disease course, and the factors influencing the outcome of patients with AOSD. METHODS: A multicenter study was used to reach sufficient patient numbers. The diagnosis of AOSD was based on the Yamaguchi criteria. The data collected included patient age, gender, age at the time of diagnosis, delay time for the diagnosis, typical AOSD rash, arthralgia, arthritis, myalgia, sore throat, lymphadenopathy, hepatomegaly, splenomegaly, pleuritis, pericarditis, and other rare findings. The laboratory findings of the patients were also recorded. The drugs initiated after the establishment of a diagnosis and the induction of remission with the first treatment was recorded. Disease patterns and related factors were also investigated. A multivariate analysis was performed to assess the factors related to remission. RESULTS: The initial data of 356 patients (210 females; 59%) from 19 centers were evaluated. The median age at onset was 32 (16-88) years, and the median follow-up time was 22 months (0-180). Fever (95.8%), arthralgia (94.9%), typical AOSD rash (66.9%), arthritis (64.6%), sore throat (63.5%), and myalgia (52.8%) were the most frequent clinical features. It was found that 254 of the 306 patients (83.0%) displayed remission with the initial treatment, including corticosteroids plus methotrexate with or without other disease-modifying antirheumatic drugs. The multivariate analysis revealed that the male sex, delayed diagnosis of more than 6 months, failure to achieve remission with initial treatment, and arthritis involving wrist/elbow joints were related to the chronic disease course. CONCLUSION: Induction of remission with initial treatment was achieved in the majority of AOSD patients. Failure to achieve remission with initial treatment as well as a delayed diagnosis implicated a chronic disease course in AOSD.


Assuntos
Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Biomarcadores , Diagnóstico Tardio , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Recidiva , Indução de Remissão , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
14.
Med Sci Monit ; 21: 3547-54, 2015 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-26574972

RESUMO

BACKGROUND Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease predominantly affecting Mediterranean populations. The gene associated with FMF is the MEFV gene, which encodes for a protein called pyrin. Mutations of pyrin lead to uncontrolled attacks of inflammation, and subclinical inflammation continues during attack-free intervals. Killer cell immunoglobulin-like receptor (KIR) genes encode HLA class I receptors expressed by NK cells. The aim this study was to look for immunogenetic determinants in the pathogenesis of FMF and find out if KIR are related to susceptibility to disease or complications like renal amyloidosis. MATERIAL AND METHODS One hundred and five patients with FMF and 100 healthy individuals were involved in the study. Isolated DNA from peripheral blood was amplified by sequence specific PCR probes and analyzed by Luminex for KIR genotypes. Fisher Exact test was used to evaluate the variation of KIR gene distribution. RESULTS All patients and healthy controls expressed the framework genes. An activator KIR gene, KIR2DS2, was significantly more frequent in FMF patients (p=0.036). Renal amyloidosis and presence of arthritis were not associated with KIR genes and genotype. KIR3DL1 gene was more common in patients with high serum CRP (p=0.016). CONCLUSIONS According to our findings, we suggest that presence of KIR2DS2, which is an activator gene for NK cell functions, might be related to the autoinflammation in FMF. The potential effect of KIR genes on amyloidosis and other clinical features requires studies with larger sample sizes.


Assuntos
Proteínas do Citoesqueleto/genética , Febre Familiar do Mediterrâneo/genética , Receptores KIR/genética , Adulto , Amiloidose/genética , Estudos de Casos e Controles , Proteínas do Citoesqueleto/imunologia , Febre Familiar do Mediterrâneo/imunologia , Febre Familiar do Mediterrâneo/patologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Imunogenética , Imunoglobulinas/genética , Imunoglobulinas/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Masculino , Mutação , Polimorfismo Genético , Pirina , Receptores KIR/imunologia
15.
Mod Rheumatol ; 25(2): 315-21, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24533558

RESUMO

We present two PHO siblings having a novel homozygous truncating mutation in HPGD. The purpose of the study was to attempt medical treatment, and to find the HPGD mutation causing the disease, in a 22-year old Turkish male and his 23-year old sister afflicted with primary hypertrophic osteoarthropathy (PHO). In combination with NSAIDs and colchicine, treatment with sulfasalazine was started in both cases, and methotrexate was added to the treatment regimen of the female patient at the end of the first year. The patients were found to be typical PHO. Ultrasonographic examination of the joints revealed synovitis and inflammation by B mode and power Doppler ultrasonography. Joint symptoms responded to sulfasalazine treatment in both patients. However, after the addition of methotrexate, the female patient had better remission. All exons of HPGD, the known disease gene, were analyzed by Sanger sequencing. A homozygous 2-bp deletion (c.310_311delCT or p.L104AfsX3) was identified. Seven relatives carrying the mutation in the heterozygous state were examined and none was found affected. Although not specific for this disease, skin, soft tissue and joint ultrasonography can be helpful for evaluation of the musculoskeletal findings in the patients.


Assuntos
Hidroxiprostaglandina Desidrogenases/genética , Mutação de Sentido Incorreto , Osteoartropatia Hipertrófica Primária/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Linhagem , Adulto Jovem
16.
Ann Rheum Dis ; 73(5): 897-901, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24570027

RESUMO

BACKGROUND: Colchicine is the main treatment for familial Mediterranean fever (FMF). However, biological agents and other treatments are available for patients who are unable to receive optimal treatment. OBJECTIVE: To develop outcome criteria that define response to treatment. METHODS: Two rounds of Delphi exercise were followed by a consensus conference enabling the definition of the criteria to be employed. Data for patients with FMF responding and resistant to their treatment were obtained from the FMF Arthritis Vasculitis and Orphan disease Research in paediatric rheumatology (FAVOR) website. The suggested criteria were analysed and validated in this patient cohort. Sensitivity/specificity measures and the ability of the score to discriminate between patients with active and inactive disease via the best cut-off score were calculated by a receiver operating characteristic analysis. RESULTS: Compliance with the maximum dose of the drug was considered essential for evaluation of the patients. Seven criteria were suggested in the consensus conference. The performance of each criterion, in differentiating between resistant and responsive patients, was tested. The final set of criteria was defined as at least 50% improvement in five of six criteria, without worsening in any one defined response to treatment with a very high sensitivity and specificity. The items of this FMF50 included: 1. Percentage change in the frequency of attacks with the treatment. 2. Percentage change in the duration of attacks with the treatment. 3. Patients/parents' global assessment of disease severity (10 cm visual analogue scale (VAS)). 4. Physicians' global assessment of disease severity (10 cm VAS). 5. Percentage change in arthritis attacks with the treatment. 6. Percentage change in C-reactive protein, erythrocyte sedimentation rate or serum amyloid A level with the treatment. CONCLUSIONS: The FMF50 produced is a user-friendly measurement tool to guide physicians and can be used in clinical trials.


Assuntos
Febre Familiar do Mediterrâneo/tratamento farmacológico , Imunossupressores/uso terapêutico , Adolescente , Adulto , Área Sob a Curva , Colchicina/uso terapêutico , Técnica Delphi , Feminino , Humanos , Masculino , Curva ROC , Sistema de Registros , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
17.
Rheumatology (Oxford) ; 53(4): 741-5, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24369413

RESUMO

OBJECTIVE: The primary aim of this study was to investigate the prevalence of amyloidosis and its related factors in a large number of FMF patients. METHODS: Fifteen centres from the different geographical regions of Turkey were included in the study. Detailed demographic and medical data based on a structured questionnaire and medical records were collected. The diagnosis of amyloidosis was based on histological proof of congophilic fibrillar deposits in tissue biopsy specimens. RESULTS: There were 2246 FMF patients. The male/female ratio was 0.87 (1049/1197). The mean age of the patients was 34.5 years (S.D. 11.9). Peritonitis was the most frequent clinical finding and it was present in 94.6% of patients. Genetic testing was available in 1719 patients (76.5%). The most frequently observed genotype was homozygous M694V mutation, which was present in 413 (24%) patients. Amyloidosis was present in 193 patients (8.6%). Male sex, arthritis, delay in diagnosis, M694V genotype, patients with end-stage renal disease (ESRD) and family history of amyloidosis and ESRD were significantly more prevalent in patients with amyloidosis compared with the amyloidosis-negative subjects. Patients with homozygous M694V mutations had a 6-fold higher risk of amyloidosis compared with the other genotypes (95% CI 4.29, 8.7, P < 0.001). CONCLUSION: In this nationwide study we found that 8.6% of our FMF patients had amyloidosis and homozygosity for M694V was the most common mutation in these patients. The latter finding confirms the association of homozygous M694V mutation with amyloidosis in Turkish FMF patients.


Assuntos
Amiloidose/etiologia , Febre Familiar do Mediterrâneo/complicações , Adulto , Amiloidose/genética , Artrite/etiologia , Proteínas do Citoesqueleto/genética , Diagnóstico Tardio , Febre Familiar do Mediterrâneo/genética , Feminino , Genótipo , Homozigoto , Humanos , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Pirina , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Turquia , Adulto Jovem
18.
Med Sci Monit ; 20: 28-34, 2014 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-24407110

RESUMO

BACKGROUND: Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activating receptors expressed by natural killer (NK) cells and regulate NK cell activity in the innate response against viral infections. The aim of this study was to determine the possibility of KIR genes and genotypes as a candidate for susceptibility to or protection against chronic hepatitis B virus (HBV) infection or spontaneous remission of the infection in a Turkish cohort. MATERIAL AND METHODS: The present study was carried out on 37 patients with chronic HBV infection, 36 patients in spontaneous remission of HBV infection, and 85 healthy subjects. Sequence-specific oligonucleotide probes analysis was used to investigate 16 KIR genes. All data were statistically analyzed by the Fisher exact test. RESULTS: The rate of inhibitory KIR2DL3 (p=0.0) and 3DS1 (p=0.0) were higher in the healthy group than the group composed of chronic HBV patients and patients with spontaneous remission. There were no statistically significant differences between the rate of AA and Bx genotypes of chronic HBV patients and patients with spontaneous remission and the control group (p>0.05). CONCLUSIONS: Our results suggest that KIR2DL3 and KIR3DS1 genes could be protector genes for HBV infection and they could be important immuno-genetic markers in determining antiviral immunity in the Turkish population.


Assuntos
Marcadores Genéticos/genética , Predisposição Genética para Doença/genética , Hepatite B/genética , Hepatite B/imunologia , Receptores KIR/genética , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Sondas de Oligonucleotídeos/genética , Turquia
19.
Sisli Etfal Hastan Tip Bul ; 58(2): 244-248, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39021690

RESUMO

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.

20.
Rheumatology (Oxford) ; 52(10): 1898-904, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23873821

RESUMO

OBJECTIVE: Patient-reported outcomes (PROs) are increasingly accepted to be among the major tools for outcome assessment in rheumatic disorders. In this study we aimed to assess quality of life (QoL), disability, anxiety and depression in patients with Takayasu's arteritis (TAK). METHODS: Patients followed with the diagnosis of TAK (n = 165) and healthy controls (HCs) (n = 109) were enrolled to the study. The 36-item Short Form Health Survey (SF-36) and hospital anxiety and depression scales (HADS) were used to assess QoL and mental status together with HAQ for disability. RESULTS: In SF-36 subscale assessment, all items were observed to be statistically lower in TAK patients; similarly HAQ scores were also higher (P < 0.001) in this group. In mental assessment, anxiety was found to be more common in TAK patients [90 (54.5%) vs 38 (34.9%), P = 0.001]. Depression also tended to be higher in TAK patients [70 (66.7%) vs 35 (33.3%)], without reaching significance (P = 0.086). Most of the SF-36 subgroup parameters were lower in TAK patients with active disease. Patients having anxiety and depression or with high HAQ scores reported worse SF-36 scores. In multivariate analysis, HADS-A, HADS-D and HAQ were associated with most SF-36 subscales. CONCLUSION: PROs demonstrate that not only general health but also physical and social functioning with physical role limitations and mental health parameters were impaired in TAK. Our results, especially in active disease, suggest that PROs such as SF-36 can be core domains of disease assessment in TAK, similar to ANCA-associated vasculitides.


Assuntos
Ansiedade/etiologia , Depressão/etiologia , Qualidade de Vida , Arterite de Takayasu/psicologia , Adulto , Ansiedade/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Psicometria , Arterite de Takayasu/epidemiologia , Arterite de Takayasu/fisiopatologia , Arterite de Takayasu/reabilitação , Turquia/epidemiologia
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