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1.
Clin Exp Rheumatol ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32242803

RESUMO

OBJECTIVES: Cytokines signaling pathway genes represent a key component of the genetic network implicated in the pathogenesis of immunoglobulin-A vasculitis (IgAV), an inflammatory vascular pathology. Interleukin (IL)17A is described as a genetic risk locus for some autoimmune diseases, such as giant cell arteritis and spondyloarthritis. Accordingly, we aimed to determine the potential influence of IL17A on the pathogenesis of IgAV. METHODS: Five IL17A tag polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909), which cover the major variability of this gene, were genotyped in 360 Caucasian patients with IgAV and 1,003 sex and ethnically matched healthy controls using TaqMan probes. RESULTS: No statistically significant differences between patients with IgAV and healthy controls were observed when each IL17A genetic variant was analysed independently. Similarly, no statistically significant differences between patients with IgAV and healthy controls were found when the five IL17A polymorphisms were evaluated combined conforming haplotypes. In addition, there were no statistically significant differences in genotype, allele and haplotype frequencies of IL17A when patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. CONCLUSIONS: Our results do not support an influence of IL17A on the pathogenesis of IgAV.

2.
Clin Exp Rheumatol ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32167874

RESUMO

OBJECTIVES: The TYK2 gene encodes a tyrosin kinase which is involved in multiple immune functions. A functional variant of this gene has been identified to play a protective role in multiple autoimmune diseases. The goal of this study was to evaluate the involvement of this variant of TYK2 in vasculitides [giant cell arteritis (GCA), ANCA-associated vasculitis (AAV) and IgA vasculitis (IgAV)] and viral infections [hepatitis C virus (HCV) and human immunodeficiency virus type I (HIV-1)]. METHODS: The study sample was composed of 13,745 European individuals. The genotyping was performed by Immunochip and TaqMan 5' allele discrimination assays and the allele frequencies were compared using PLINK. RESULTS: Although the results obtained did not reach the genome-wide level of significance, p-values at nominal significance were observed, suggesting that the TYK2 variant provides protection against two vasculitides: GCA (p=5.94E-3; OR (95%CI) = 0.56 (0.37-0.85) and AAV (p=6.79E-3; OR (95%CI) = 0.65 (0.47-0.89). However, this variant was not found to be associated with IgAV. No evidence was gained that the TYK2 variant confers susceptibility to HCV and HIV-1 infection. CONCLUSIONS: This is the first study to propose the association between the TYK2 and both GCA and AAV. Our findings also suggest that TYK2 does not play a relevant role in IgAV or in susceptibility to HCV and HVI-1.

3.
Sci Rep ; 10(1): 3355, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32098994

RESUMO

The major environmental risk factor for rheumatoid arthritis (RA) is smoking, which according to a widely accepted model induces protein citrullination in the lungs, triggering the production of anti-citrullinated protein antibodies (ACPA) and RA development. Nevertheless, some research findings do not fit this model. Therefore, we obtained six independent cohorts with 2253 RA patients for a detailed analysis of the association between smoking and RA autoantibodies. Our results showed a predominant association of smoking with the concurrent presence of the three antibodies: rheumatoid factor (RF), ACPA and anti-carbamylated protein antibodies (ACarPA) (3 Ab vs. 0 Ab: OR = 1.99, p = 2.5 × 10-8). Meta-analysis with previous data (4491 patients) confirmed the predominant association with the concurrent presence of the three antibodies (3 Ab vs. 0 Ab: OR = 2.00, p = 4.4 ×10-16) and revealed that smoking was exclusively associated with the presence of RF in patients with one or two antibodies (RF+1+2 vs. RF-0+1+2: OR = 1.32, p = 0.0002). In contrast, no specific association with ACPA or ACarPA was found. Therefore, these results showed the need to understand how smoking favors the concordance of RA specific antibodies and RF triggering, perhaps involving smoking-induced epitope spreading and other hypothesized mechanisms.

4.
Sci Rep ; 10(1): 1415, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996780

RESUMO

MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. No significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with a usual interstitial pneumonia (UIP) pattern when compared to those with a non-UIP pattern. However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD.

5.
Clin Exp Rheumatol ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31969232

RESUMO

OBJECTIVES: Patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) have an increased premature prevalence of atherosclerosis. We aimed to determine whether there are differences in the prevalence of classic cardiovascular risk factors between SLE and RA. We also analysed the effect of traditional cardiovascular risk factors on the development of subclinical atherosclerosis in both conditions and if some disease-characteristic features are associated with these traditional cardiovascular risk factors. METHODS: This was a cross-sectional study encompassing 602 individuals, 276 SLE and 326 RA patients. Subclinical atherosclerosis (presence of carotid plaques and carotid intima-media thickness [cIMT]) was determined by carotid ultrasonography. A multivariable regression analysis was performed to evaluate whether classic cardiovascular-related risk factors differentially influence subclinical carotid atherosclerosis in SLE compared to RA patients. RESULTS: Age (interaction factor [if] p=0.000), hypertension (if p=0.034), and diabetes (if p=0.037) had a higher effect on cIMT in RA than in SLE subjects. However, these traditional cardiovascular factors did not yield different effects on the presence of carotid plaques in RA and SLE when the univariate interaction was analysed. In addition, no differences were found in the influence of hypertension, diabetes, dyslipidaemia or current smoking on cIMT or carotid plaque after adjusting for demographics, the presence of other traditional cardiovascular factors, and disease-related data. Moreover, the additive effect of several cardiovascular risk factors on the subclinical carotid atherosclerosis did not differ between the two diseases. CONCLUSIONS: The influence of traditional cardiovascular risk factors on cIMT and carotid plaque is similar in RA and SLE.

7.
Neurol Clin ; 37(2): 219-234, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30952406

RESUMO

"Vasculitides are a heterogeneous group of inflammatory diseases of blood vessels in which genetic variation plays an important role in their susceptibility and clinical spectrum. Because of the use of novel technologies and the increase of the sample size of the study cohorts, the knowledge of the genetic background of vasculitides has considerably expanded during the last years. However, few insights have been obtained regarding the genetics underlying severe clinical phenotypes, such as those related to the nervous system. In this review the authors provide an updated overview of the genetic landscape behind vasculitis predisposition and development of neurologic manifestations."


Assuntos
Predisposição Genética para Doença , Doenças do Sistema Nervoso/etiologia , Vasculite/complicações , Vasculite/genética , Humanos
8.
Nefrologia ; 39(5): 523-530, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30902505

RESUMO

INTRODUCTION: IgA nephropathy (IgAN) is the most common and heterogeneous glomerular nephropathy. Several strategies have been used to determine the risk of progression to ESRD. We evaluate the prognostic significance and correlate the IgAN progression calculator (IgANPC) and the Oxford/MEST-C score in our population. MATERIAL AND METHODS: We performed a retrospective study of biopsied patients with diagnosis of IgA nephropathy from 1990 to 2015. We classified the biopsies using MEST-C score and we correlated the score to clinical evolution. We also calculated the risk of progression with the online IgANPC at the time of the biopsy. RESULTS: We analysed 48 biopsies, 83% of which were men with a mean age of 45 years at the time of the biopsy. Patients with a biopsy E1 according to MEST-C score had a higher IgANPC score than those with E0 (P=.021). The Pearson's correlation for the percentage of crescents and the IgANPC risk score was statistically significant (P=.014) with r=0.357. The percentage of patients with eGFR above 30 ml/min at 10 years was 100% for the low-risk group (group 1 of IgANPC), and 0% for the high-risk group (group 3), log rank P=0.001. The log rank comparison for variables of the MEST-C score, presented statistically significant results between E (0.036) and S (0.022) and the eGFR time<30 ml/min. A statistically significant relationship was also observed between T1 and eGFR<30 ml/min. The multivariate Cox regression analysis for IgANPC and eGFR<30 ml/min demonstrated a strong correlation (P=.016) between the risk group and eGFR <30 ml/min. CONCLUSION: In our study population, the IgANPC predicts the time to eGFR<30 ml/min, and adds information independent of the MEST. The MEST-C classification and IgANPC are useful and independent ÿolos for prognostic prediction, but more studies are needed to validate its use in the general population.

9.
Arthritis Rheumatol ; 71(3): 351-360, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30251476

RESUMO

OBJECTIVE: To investigate the genetic background influencing the development of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA). METHODS: We performed a genome-wide association study (GWAS) in which, after quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analyzed in 2,989 RA patients of European origin. Data on subclinical atherosclerosis, obtained through assessment of carotid intima-media thickness (CIMT) and presence/absence of carotid plaques by carotid ultrasonography, were available for 1,355 individuals. RESULTS: A genetic variant of the RARB gene (rs116199914) was associated with CIMT values at the genome-wide level of significance (minor allele [G] ß coefficient 0.142, P = 1.86 × 10-8 ). Interestingly, rs116199914 overlapped with regulatory elements in tissues related to CV pathophysiology and immune cells. In addition, biologic pathway enrichment and predictive protein-protein relationship analyses, including suggestive GWAS signals of potential relevance, revealed a functional enrichment of the collagen biosynthesis network related to the presence/absence of carotid plaques (Gene Ontology no. 0032964; false discovery rate-adjusted P = 4.01 × 10-3 ). Furthermore, our data suggest potential influences of the previously described candidate CV risk loci NFKB1, MSRA, and ZC3HC1 (P = 8.12 × 10-4 , P = 5.94 × 10-4 , and P = 2.46 × 10-4 , respectively). CONCLUSION: The present findings strongly suggest that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA.


Assuntos
Regiões 3' não Traduzidas/genética , Artrite Reumatoide/genética , Artrite Reumatoide/fisiopatologia , Aterosclerose/genética , Espessura Intima-Media Carotídea , Receptores do Ácido Retinoico/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Artérias Carótidas/diagnóstico por imagem , Proteínas de Ciclo Celular/genética , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Metionina Sulfóxido Redutases/genética , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/genética , Proteínas Nucleares/genética , Fatores de Risco
10.
J Rheumatol ; 46(3): 229-236, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30275261

RESUMO

OBJECTIVE: In nondiabetic healthy individuals, insulin secretion and sensitivity are linked by a negative feedback loop characterized by a hyperbolic function. We aimed to study the association of traditional insulin resistance (IR) factors with insulin secretion and sensitivity, and to determine whether the hyperbolic equilibrium of this relation is preserved in patients with rheumatoid arthritis (RA). METHODS: This was a cross-sectional study encompassing 361 nondiabetic individuals: 151 with RA and 210 controls. Insulin, C-peptide, and IR indices by homeostatic model (HOMA2) were assessed. A multivariable analysis was performed to evaluate the differences in the correlation of traditional IR-related factors with glucose homeostasis molecules, as well as IR indices between patients and controls. Nonlinear regression analysis was used to assess the hyperbolic relation of insulin sensitivity and secretion. RESULTS: HOMA2-IR indices were higher in patients with RA than controls. Hepatic insulin extraction, as assessed by the insulin:C-peptide molar ratio, was lower in patients with RA after multivariable analysis (0.08 ± 0.02 vs 0.14 ± 0.07, p < 0.001). Traditional IR-related factors showed significantly lower adjusted correlation coefficients with IR indices in patients with RA. The association between insulin sensitivity and secretion showed a different hyperbolic relation in patients with RA: the variability explained by the curve was lower in RA (nonlinear r2 = 0.845 vs r2 = 0.928, p = 0.001) and ß coefficients (-0.74, 95% CI -0.77 to -0.70 vs -1.09, 95% CI -1.17 to -1.02, ng/ml, p < 0.001) were different in RA. CONCLUSION: The traditional factors associated with IR in healthy individuals are less related to IR in patients with RA. Insulin sensitivity and secretion yield a different hyperbolic equilibrium in RA.

11.
Clin Exp Rheumatol ; 37(3): 373-379, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30299246

RESUMO

OBJECTIVES: The chemokine molecule CXCL5 (C-X-C motif chemokine ligand 5, also known as epithelial neutrophil activating peptide 78 -ENA78-) constitutes a link between obesity, inflammation and insulin resistance (IR) in the general population. CXCL5 has also been found to play a role in rheumatoid arthritis (RA) pathogenesis. Since chronic inflammation promotes IR and impairs pancreatic beta cell function in RA patients, we assessed the role of CXCL5 in the development of IR in RA. METHODS: Cross-sectional study that encompassed 141 non-diabetic patients with RA. IR assessed by homeostatic model assessment (HOMA2), insulin and C-peptide serum levels and lipid profile, and CXCL5 serum levels were studied. Regression analysis was performed to evaluate how CXCL5 was related to IR, disease activity, and disease characteristics in RA patients. RESULTS: HOMA2-IR indexes showed high values for both IR and beta cell production (%B), and low insulin sensitivity (%S) in patients with RA. C reactive protein (beta coef. 0.2 [95%CI -1.5-1.9], p=0.80) and disease activity through DAS28 (beta coef. 13 [95%CI -14-41], p=0.34) revealed no relation with CXCL5. Other disease characteristics, such as disease duration, serological status, or use of methotrexate or anti-TNF alpha therapies, were not associated with CXCL5 serum levels. While glucocorticoids were related to insulin, C-peptide serum levels, and HOMA2-IR and HOMA2-%B-C peptide, the use of prednisone was not associated with CXCL5 serum levels. Insulin and C peptide serum levels and IR indexes showed strong correlations among each other, but not with CXCL5 (insulin r2=-0.034, p=0.69; C peptide r2=-0.050, p=0.56). CONCLUSIONS: CXCL5 is not related to IR in RA patients. Therefore, the mechanisms leading to IR in patients with RA may be different from those in the general population.


Assuntos
Artrite Reumatoide , Quimiocina CXCL5/sangue , Resistência à Insulina , Peptídeos/sangue , Artrite Reumatoide/fisiopatologia , Estudos Transversais , Feminino , Humanos , Resistência à Insulina/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Pessoa de Meia-Idade , Neutrófilos , Fator de Necrose Tumoral alfa
12.
Clin Exp Rheumatol ; 37(3): 465-473, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30418124

RESUMO

OBJECTIVES: In patients with rheumatoid arthritis (RA), insulin resistance (IR), a component of the metabolic syndrome, is closely linked to the systemic inflammation induced by proinflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-6. In the present study, we aimed to assess if an intravenous administration of the anti-IL-6 receptor tocilizumab may yield a rapid improvement of IR in RA. METHODS: 50 consecutive non-diabetic patients with RA refractory to methotrexate, undergoing periodic treatment with tocilizumab, were studied. Besides disease activity, serum insulin, insulin/glucose ratio, insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) indexes were assessed immediately before and 1 hour after the end of an intravenous administration of tocilizumab (given in saline solution over 60 minutes). RESULTS: When comparing baseline data (immediately before) and 1 hour after finishing tocilizumab administration, we observed a dramatic decrease of the serum insulin levels and insulin/glucose ratio. Also, a statistically significant reduction of IR (HOMA-IR: mean± standard deviation immediately before: 2.62±2.03 vs. 1.65±1.15 1 hour after the end of the infusion (p<0.01) and a statistically significant increase of insulin sensitivity (QUICKI immediately before 0.34±0.03 vs. 0.37±0.04 1 hour after the end of tocilizumab infusion (p<0.01) was observed. CONCLUSIONS: The intravenous administration of tocilizumab yields a rapid beneficial effect on IR and insulin sensitivity in non-diabetic RA patients. These findings support the potential beneficial effect of the IL-6 blockade on the mechanisms associated with the development of metabolic syndrome and cardiovascular disease in patients with RA.


Assuntos
Artrite Reumatoide , Resistência à Insulina , Receptores de Interleucina-6/antagonistas & inibidores , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Glicemia/análise , Humanos , Insulina/sangue , Interleucina-6 , Fator de Necrose Tumoral alfa
13.
Sci Rep ; 8(1): 13728, 2018 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-30213986

RESUMO

Calprotectin (CPT) is released during inflammation, also in the context of atherosclerosis. The link between CPT and the atherosclerotic process was evaluated in several diseases. However, studies in axial spondyloarthritis (axSpA), associated with a high incidence of subclinical atherosclerosis, are scarce. Therefore, we assessed the association of CPT with subclinical atherosclerosis and metabolic risk factors in axSpA. CPT serum levels were measured by enzyme-linked immunosorbent assay in 163 axSpA patients and 63 controls. Subclinical atherosclerosis was determined in patients by carotid ultrasonography (assessing the presence/absence of carotid plaques and carotid intima-media thickness [cIMT]). Data on inflammation, disease activity, lipid profile and treatment were collected to evaluate its relationship with CPT. axSpA patients evidenced lower CPT levels than controls. CPT showed no association with plaques or cIMT in axSpA. CPT and HDL-cholesterol negatively correlated, while a positive association of CPT with the atherogenic index was disclosed. Additionally, axSpA patients with C-reactive protein values at diagnosis higher than 3 mg/L displayed higher CPT levels. Our study shows no relationship between CPT and markers of subclinical atherosclerosis in axSpA. Nevertheless, it demonstrates an association of CPT with adverse lipid profiles and inflammatory biomarkers, which could further influence on the development of atherosclerosis.


Assuntos
Aterosclerose/sangue , Inflamação/sangue , Complexo Antígeno L1 Leucocitário/sangue , Lipídeos/sangue , Espondilartrite/sangue , Adulto , Aterosclerose/patologia , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Artérias Carótidas/patologia , Espessura Intima-Media Carotídea , HDL-Colesterol/sangue , Feminino , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Espondilartrite/patologia , Ultrassonografia
14.
Curr Rheumatol Rep ; 20(5): 24, 2018 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-29611051

RESUMO

PURPOSE OF REVIEW: The purpose of the study is to perform an update on the current knowledge on genetics, clinical manifestations, and therapy in immunoglobulin A vasculitis (IgAV) (Henoch-Schönlein purpura). RECENT FINDINGS: A strong genetic predisposition in individuals with IgAV was confirmed. It was due to the association with the HLA class II region that in people of European background is mainly related to HLA-DRB1*01 allele. Recent reports support the claim that kidney disease is more common in adults than in children with IgAV. The clinical spectrum and outcome of adults with IgAV depends on the age of onset. Relapses are not uncommon in IgAV. The presence of renal impairment or proteinuria excretion exceeding 1 g/24 h at the time of disease diagnosis and the degree of renal damage on the kidney biopsy are the best predictors of end-stage renal failure in adults with IgAV. The levels of urinary IgA at the onset of the disease may predict a poor renal outcome. The use of prednisone does not seem to prevent persistent kidney disease in children with IgAV. No additional benefit of adding cyclophosphamide to glucocorticoids in adults with IgAV was found. Rituximab seems to be a promising therapy in the management of adults with IgAV. In this overview, we focus on the genetics, clinical manifestations, and therapy of IgA vasculitis, emphasizing the main differences in the clinical expression of the disease between children and adults.


Assuntos
Imunoglobulina A/análise , Púrpura de Schoenlein-Henoch/tratamento farmacológico , Púrpura de Schoenlein-Henoch/genética , Predisposição Genética para Doença , Glucocorticoides/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Púrpura de Schoenlein-Henoch/diagnóstico , Rituximab/uso terapêutico
15.
Semin Arthritis Rheum ; 48(1): 22-27, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29422324

RESUMO

OBJECTIVE: Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA. METHODS: National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA. RESULTS: 63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean ± standard deviation age at the time of the study was 63.2 ± 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 ± 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events. CONCLUSION: ABA appears to be an effective in RA-associated ILD.


Assuntos
Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Idoso , Artrite Reumatoide/complicações , Feminino , Humanos , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
Clin Exp Rheumatol ; 36(2): 302-309, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29303699

RESUMO

OBJECTIVES: Due to the high incidence of cardiovascular disease in axial spondyloarthritis (axSpA), the search of potential biomarkers that may help to identify patients with high cardiovascular risk is of main importance. Therefore, in this study we assessed the implication of osteoprotegerin (OPG) and sclerostin (SCL), two biomarkers associated with cardiovascular disease and bone metabolism, in the clinical spectrum and atherosclerotic disease of patients with axSpA. METHODS: OPG and SCL serum levels were determined in 163 axSpA Spanish patients (119 ankylosing spondylitis and 44 non-radiographic axSpA) and 63 healthy controls by enzyme-linked immunosorbent assay. Carotid ultrasound was performed in axSpA patients to determine the presence of subclinical atherosclerosis (by the identification of abnormally increased carotid intima-media thickness [cIMT] and presence of plaques). RESULTS: Patients displayed higher OPG but lower SCL levels than controls (p=0.02 and 0.001, respectively). Association of these molecules with some metabolic syndrome features was seen. In this regard, OPG negatively correlated with body mass index (p=0.04) whereas SCL levels were higher in hypertensive patients (p=0.01) and in men (p=0.002). However, serum OPG and SCL were not significantly correlated with cIMT values or presence of plaques when data were adjusted by age at the time of the study, sex, classic cardiovascular risk factors and anti-TNF therapy. CONCLUSIONS: Our results suggest an association of OPG and SCL in axSpA with some metabolic syndrome features that are associated with an increased risk of CV disease.


Assuntos
Proteínas Morfogenéticas Ósseas/sangue , Doenças Cardiovasculares/etiologia , Osteoprotegerina/sangue , Espondilartrite/complicações , Adulto , Idoso , Espessura Intima-Media Carotídea , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade
17.
PLoS One ; 13(1): e0190568, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29300768

RESUMO

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease which has been associated with an increased risk of adverse cardiovascular (CV) outcomes. Adequate stratification of the CV risk is an issue of major importance in patients with HS. To analyze the usefulness of carotid ultrasound (US) assessment for the CV disease risk stratification compared with a traditional score, the Framingham risk score (FRS), in a series of patients with HS. METHODS: Cross-sectional study of 60 patients with HS without history of CV events, diabetes mellitus or chronic kidney disease. Information on CV risk factors was collected and the FRS was calculated. Thus, the patients were classified into low, intermediate and high-CV disease risk categories based on FRS. Carotid US was performed in all participants, and the presence of atherosclerotic plaques was considered as a marker of high CV risk. RESULTS: HS patients had a mean age of 45.1±10.2 years, and 55% were female. The median FRS was 5.7 (IQR: 3.1-14.7). Twenty-four (40%) of the patients were classified into the low risk group, 28 (46.7%) in the intermediate risk group, and 8 (13.3%) into the FRS-high risk category. Noteworthy, carotid US revealed that about one-third of the patients (17/52; 32.6%) in the FRS-based low and intermediate risk categories had carotid plaques, and, therefore, they were reclassified into a high-risk category. CONCLUSION: CV risk in HS patients may be underestimated by using the FRS. Carotid US may be useful to improve the CV risk stratification of patients with HS.


Assuntos
Doenças Cardiovasculares/complicações , Artérias Carótidas/diagnóstico por imagem , Hidradenite Supurativa/complicações , Estudos Transversais , Humanos , Curva ROC
18.
Autoimmun Rev ; 17(3): 301-315, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29353097

RESUMO

Immunoglobulin-A vasculitis (IgAV) is classically a childhood small-sized blood vessel vasculitis with predominant involvement of the skin. Gastrointestinal and joint manifestations are common in patients diagnosed with this condition. Nephritis, which is more severe in adults, constitutes the most feared complication of this vasculitis. The molecular bases underlying the origin of IgAV have not been completely elucidated. Nevertheless, several pieces of evidence support the claim that genes play a crucial role in the pathogenesis of this disease. The human leukocyte antigen (HLA) region is, until now, the main genetic factor associated with IgAV pathogenesis. Besides a strong association with HLA class II alleles, specifically HLA-DRB1 alleles, HLA class I alleles also seem to influence on the predisposition of this disease. Other gene polymorphisms located outside the HLA region, including those coding cytokines, chemokines, adhesion molecules as well as those related to T-cells, aberrant glycosylation of IgA1, nitric oxide production, neoangiogenesis, renin-angiotensin system and lipid, Pyrin and homocysteine metabolism, may be implicated not only in the predisposition to IgAV but also in its severity. An update of the current knowledge of the genetic component associated with the pathogenesis of IgAV is detailed in this review.


Assuntos
Imunoglobulina A/genética , Polimorfismo Genético/genética , Púrpura de Schoenlein-Henoch/genética , Humanos , Imunoglobulina A/imunologia
19.
Ann Rheum Dis ; 77(4): 589-595, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29374629

RESUMO

OBJETIVE: Systemic vasculitides represent a heterogeneous group of rare complex diseases of the blood vessels with a poorly understood aetiology. To investigate the shared genetic component underlying their predisposition, we performed the first cross-phenotype meta-analysis of genetic data from different clinically distinct patterns of vasculitis. METHODS: Immunochip genotyping data from 2465 patients diagnosed with giant cell arteritis, Takayasu's arteritis, antineutrophil cytoplasmic antibody-associated vasculitis or IgA vasculitis as well as 4632 unaffected controls were analysed to identify common susceptibility loci for vasculitis development. The possible functional consequences of the associated variants were interrogated using publicly available annotation data. RESULTS: The strongest association signal corresponded with an intergenic polymorphism located between HLA-DQB1 and HLA-DQA2 (rs6932517, P=4.16E-14, OR=0.74). This single nucleotide polymorphism is in moderate linkage disequilibrium with the disease-specific human leucocyte antigen (HLA) class II associations of each type of vasculitis and could mark them. Outside the HLA region, we identified the KDM4C gene as a common risk locus for vasculitides (highest peak rs16925200, P=6.23E-07, OR=1.75). This gene encodes a histone demethylase involved in the epigenetic control of gene expression. CONCLUSIONS: Through a combined analysis of Immunochip data, we have identified KDM4C as a new risk gene shared between systemic vasculitides, consistent with the increasing evidences of the crucial role that the epigenetic mechanisms have in the development of complex immune-mediated conditions.


Assuntos
Loci Gênicos/genética , Histona Desmetilases com o Domínio Jumonji/genética , Fenótipo , Vasculite Sistêmica/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Estudos de Casos e Controles , Epigênese Genética , Feminino , Loci Gênicos/imunologia , Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Arterite de Células Gigantes/imunologia , Antígenos HLA-DQ/genética , Antígenos HLA-DQ/imunologia , Cadeias beta de HLA-DQ/genética , Cadeias beta de HLA-DQ/imunologia , Humanos , Histona Desmetilases com o Domínio Jumonji/imunologia , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único , Análise Serial de Proteínas , Vasculite Sistêmica/imunologia , Arterite de Takayasu/genética , Arterite de Takayasu/imunologia
20.
Clin Exp Rheumatol ; 36(3): 421-427, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29352842

RESUMO

OBJECTIVES: Amylin, which is co-secreted with insulin, plays a role in glycemic regulation and is impaired in type 2 diabetes. In the present study we assess, for the first time, the implication of amylin in the development of insulin resistance (IR) in rheumatoid arthritis (RA). METHODS: This was a cross-sectional study involving 361 non-diabetic individuals, 151 patients with RA and 210 sex-matched controls. Insulin, C-peptide, amylin, lipoprotein serum concentrations, and IR indexes by homeostatic model assessment (HOMA2) were evaluated in patients and controls. A multivariable analysis, adjusted for IR-related factors, was performed to determine the differences between patients and controls vis-à-vis amylin and how it is related to IR in RA. RESULTS: Insulin, C-peptide and HOMA2-IR indexes were higher in RA patients than in controls. Amylin serum levels were found to be upregulated in RA patients compared to controls (1.36 ± 0.81 vs. 1.79 ± 1.51 ng/ml, p=0.011), although this difference was lost after adjusting for covariates (p=0.46). While amylin positively correlated with the presence of rheumatoid factor (beta coef. 0.90 [95%CI -0.23-1.56], p=0.009) and SDAI (beta coef 0.01 [95%CI 0.00-0.03], p=0.034), no significant association with other disease activity scores, glucocorticoid intake, methotrexate use or TNF-alpha inhibitors was found. CONCLUSIONS: IR in RA does not appear to be mediated by amylin. This would imply that the mechanisms associated with IR in RA patients differ from those at work in type 2 diabetes.


Assuntos
Artrite Reumatoide/metabolismo , Resistência à Insulina , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Adulto , Idoso , Antirreumáticos/uso terapêutico , Apolipoproteína A-I/metabolismo , Apolipoproteínas B/metabolismo , Artrite Reumatoide/tratamento farmacológico , Peptídeo C/metabolismo , Estudos de Casos e Controles , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Estudos Transversais , Feminino , Humanos , Insulina/metabolismo , Lipoproteína(a)/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fator Reumatoide
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