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1.
Clin Exp Rheumatol ; 2018 Nov 07.
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.

2.
Arthritis Rheumatol ; 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30251476

RESUMO

OBJECTIVE: A genome-wide association study (GWAS) was conducted to shed light into the genetic background influencing the development of cardiovascular (CV) disease in patients diagnosed with rheumatoid arthritis (RA). METHODS: After quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analysed in 2,989 RA patients from European origin. Data on subclinical atherosclerosis, obtained by carotid ultrasonography through assessment of carotid intima-media thickness (cIMT) and presence/absence of carotid plaques, 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): beta (ß) coefficient=0.142, P=1.86E-08). Interestingly, rs116199914 overlapped with regulatory elements in tissues related to CV pathophysiology and immune cells. In addition, biological 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 (GO:0032964, PFDR =4.01E-03). Furthermore, our data suggest a potential influence of the previously described candidate CV risk loci NFKB1, MSRA and ZC3HC1 (P=8.12E-04, P=5.94E-04 and P=2.46E-04, respectively). CONCLUSION: Our study strongly suggests that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA. This article is protected by copyright. All rights reserved.

3.
Sci Rep ; 8(1): 13728, 2018 Sep 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.

4.
Arthritis Res Ther ; 20(1): 195, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30157925

RESUMO

BACKGROUND: This study aimed to determine whether, besides carotid ultrasound (US), a lateral lumbar spine radiography may also help identify ankylosing spondylitis (AS) patients at high risk of cardiovascular (CV) disease. METHODS: A set of 125 AS patients older than 35 years without a history of CV events, diabetes mellitus, or chronic kidney disease was recruited. Carotid US and lateral lumbar spine radiography were performed in all of them. The CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC-SCORE) algorithm. Presence of carotid plaques was defined following the Mannheim Carotid Intima-media Thickness and Plaque Consensus. Abdominal aortic calcium (AAC) in a plain radiography was defined as calcific densities visible in an area parallel and anterior to the lumbar spine. RESULTS: Carotid US showed higher sensitivity than lateral lumbar spine radiography to detect high CV risk in the 54 patients with moderate TC-SCORE (61% versus 38.9%). Using carotid plaques as the gold standard test, a predictive model that included a TC-SCORE ≥ 5% or the presence of AAC in the lateral lumbar spine radiography in patients with both moderate and low CV risk (< 5%) according to the TC-SCORE yielded a sensitivity of 50.9% with a specificity of 95.7% to identify high/very high CV-risk AS patients. A positive correlation between AAC and carotid plaques was observed (r2 = 0.49, p < 0.001). CONCLUSIONS: A lateral lumbar spine radiography is a useful tool to identify patients with AS at high risk of CV disease.

5.
Int J Rheumatol ; 2018: 1847894, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29666651

RESUMO

Objective: To determine if the use of the relative risk (RR) chart score may help to identify young ankylosing spondylitis (AS) patients at high risk of cardiovascular (CV) disease. Methods: 73 AS patients younger than 50 years were assessed. CV risk was calculated according to the total cholesterol systematic coronary risk evaluation (TC-SCORE) and the RR chart score. C-reactive protein (CRP) value at disease diagnosis and carotid ultrasound data were also analyzed. Results: Twenty (27.4%) patients exhibited carotid plaques being classified into the category of very high CV risk. None of them was found to have a high/very high TC-SCORE. CRP > 3 mg/L at disease diagnosis was associated with the presence of carotid plaques (odds ratio 5.66, p = 0.03). Whereas only 5 (14.2%) of the 35 patients with RR = 1 had carotid plaques, 15 (39.5%) of 38 with RR > 1 showed plaques. A model that included the performance of carotid US in patients with RR > 1 who had CRP > 3 mg/L allowed us to identify 60% of very high risk patients, with a specificity of 77.4%. Conclusions: RR chart score assessment may help to identify young AS patients at high risk of CV disease.

6.
Clin Exp Rheumatol ; 36(2): 302-309, 2018 Mar-Apr.
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
7.
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
8.
Clin Exp Rheumatol ; 36(1): 73-80, 2018 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28850022

RESUMO

OBJECTIVES: To determine the ability of Coronary Artery Calcification Score (CACS) and carotid ultrasonography (US) to detect high cardiovascular (CV) risk axial spondyloarthritis (ax-SpA) patients. METHODS: CACS and carotid plaques were assessed in 66 consecutive ax-SpA patients (51 fulfilling criteria for ankylosing spondylitis and 15 for non-radiological ax-SpA) without history of CV events. The Systematic Coronary Risk Evaluation (SCORE) calculated using total cholesterol (TC-SCORE) was assessed in 64 patients without diabetes mellitus or chronic kidney disease. RESULTS: The mean age of the patients and the median disease duration since the onset of symptoms were 49.3 and 14.5 years. HLA-B27 was positive in 47 (75%) patients. CV risk was categorised according to the TC-SCORE as low (<1%; n=33), moderate (≥1% and<5%; n=30) and high/very high risk (≥5%; n=1). Most patients with low TC-SCORE (27/33; 82%) had normal CACS (zero), and only 1/33 had CACS >100. However, carotid plaques were observed in patients with CACS=0 (12/37; 32%) and CACS 1-100 (10/16; 62%). The sensitivity to detect high/very high CV risk using only the TC-SCORE was very low as the algorithm only detected 1/33 (3%) of patients with high/very high CV risk. Ten of 33 (30%) high/very high CV risk patients were identified using a chart TC-SCORE risk ≥5% plus the presence of CACS ≥100 in patients with moderate TC-SCORE. The replacement of CACS with carotid US identified a higher number of high/very high CV risk patients (22/33; 67%). CONCLUSIONS: Carotid US is more sensitive than CACS for the detection of high CV risk in ax-SpA patients.


Assuntos
Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Espondilite Anquilosante/complicações , Calcificação Vascular/diagnóstico por imagem , Adulto , Doenças Assintomáticas , Doenças das Artérias Carótidas/etiologia , Doença da Artéria Coronariana/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Espondilite Anquilosante/diagnóstico , Calcificação Vascular/etiologia
9.
Sci Rep ; 7(1): 10525, 2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28874816

RESUMO

Several protein tyrosine phosphatase non-receptor 22 (PTPN22) single-nucleotide polymorphisms (SNPs) have been significantly related with rheumatoid arthritis (RA) susceptibility. Nevertheless, its potential influence on PTPN22 expression in RA has not been completely elucidated. Furthermore, PTPN22 binds to C-Src tyrosine kinase (CSK) forming a key complex in autoimmunity. However, the information of CSK gene in RA is scarce. In this study, we analyzed the relative PTPN22 and CSK expression in peripheral blood from 89 RA patients and 43 controls to determine if the most relevant PTPN22 (rs2488457, rs2476601 and rs33996649) and CSK (rs34933034 and rs1378942) polymorphisms may influence on PTPN22 and CSK expression in RA. The association between PTPN22 and CSK expression in RA patients and their clinical characteristics was also evaluated. Our study shows for the first time a marked down-regulation of PTPN22 expression in RA patients carrying the risk alleles of PTPN22 rs2488457 and rs2476601 compared to controls (p = 0.004 and p = 0.007, respectively). Furthermore, CSK expression was significantly lower in RA patients than in controls (p < 0.0001). Interestingly, a reduced PTPN22 expression was disclosed in RA patients with ischemic heart disease (p = 0.009). The transcriptional suppression of this PTPN22/CSK complex may have a noteworthy clinical relevance in RA patients.

10.
Sci Rep ; 7(1): 5088, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28698626

RESUMO

The genetic component of Immunoglobulin-A (IgA) vasculitis is still far to be elucidated. To increase the current knowledge on the genetic component of this vasculitis we performed the first genome-wide association study (GWAS) on this condition. 308 IgA vasculitis patients and 1,018 healthy controls from Spain were genotyped by Illumina HumanCore BeadChips. Imputation of GWAS data was performed using the 1000 Genomes Project Phase III dataset as reference panel. After quality control filters and GWAS imputation, 285 patients and 1,006 controls remained in the datasets and were included in further analysis. Additionally, the human leukocyte antigen (HLA) region was comprehensively studied by imputing classical alleles and polymorphic amino acid positions. A linkage disequilibrium block of polymorphisms located in the HLA class II region surpassed the genome-wide level of significance (OR = 0.56, 95% CI = 0.46-0.68). Although no polymorphic amino acid positions were associated at the genome-wide level of significance, P-values of potential relevance were observed for the positions 13 and 11 of HLA-DRB1 (P = 6.67E-05, P = 1.88E-05, respectively). Outside the HLA, potential associations were detected, but none of them were close to the statistical significance. In conclusion, our study suggests that IgA vasculitis is an archetypal HLA class II disease.

11.
J Dermatolog Treat ; 28(8): 726-730, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28489469

RESUMO

PURPOSE: Psoriasis patients have high risk of atherosclerosis, characterized by endothelial dysfunction. We aimed to study the association of the endothelial activation biomarkers monocyte chemoattractant protein 1 (MCP-1), soluble (s) E-selectin and P-selectin with disease activity and severity in psoriasis patients treated with anti-TNF-α therapy. Also, to evaluate the relationship of metabolic syndrome features with these biomarkers and the effect of anti-TNF-α therapy on these molecules. METHODS: Twenty-nine consecutive non-diabetic patients with moderate-to-severe psoriasis who underwent 6 months of anti-TNF-α-adalimumab therapy were studied. Metabolic and clinical evaluation was performed prior to anti-TNF-α treatment (time 0) and 6 months later. MCP-1, sE-selectin and sP-selectin serum levels were determined by ELISA. RESULTS: Dyslipidemic and obese patients showed higher MCP-1 levels at month 6 from the onset of anti-TNF-α therapy (p = .05 and .01, respectively). sE-selectin positively correlated with pro-inflammatory molecules such as asymmetric dimethylarginine, sP-selectin and resistin at baseline and month 6 (p < .05). sE-selectin levels significantly reduced after 6 months of therapy (p = .0006). CONCLUSIONS: Metabolic syndrome features are associated with endothelial activation in patients with moderate-to-severe psoriasis. Adalimumab therapy led to a reduction in sE-selectin levels, supporting the beneficial effect of anti-TNF-α therapy on mechanisms associated with the development of atherosclerosis in psoriasis.


Assuntos
Adalimumab/uso terapêutico , Selectina E/sangue , Psoríase/tratamento farmacológico , Adulto , Biomarcadores/sangue , Quimiocina CCL2/sangue , Dislipidemias/complicações , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Selectina-P/sangue , Psoríase/complicações , Psoríase/patologia , Resistina/sangue , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/imunologia
12.
Sci Rep ; 7: 40303, 2017 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-28059143

RESUMO

A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA.


Assuntos
Artrite Reumatoide/genética , Aterosclerose/complicações , Aterosclerose/genética , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Espanha
13.
Clin Exp Rheumatol ; 34(6): 1013-1019, 2016 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27606890

RESUMO

OBJECTIVES: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked with cardiovascular risk. The purpose of the present study was to examine whether PCSK9 levels are related to both abnormalities in the lipid profile and the severe atherosclerosis that occur in rheumatoid arthritis (RA) patients. METHODS: Cross-sectional study that encompassed 520 individuals; 326 patients with RA and 194 age- and sex-matched controls. PCSK9 and lipoproteins serum concentrations, standard lipid profile and carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients and controls. A multivariable analysis, adjusted for standard cardiovascular risk factors, was performed to evaluate the influence of PCSK9 on RA related dyslipidaemia and subclinical carotid atherosclerosis. RESULTS: After adjusting for classical cardiovascular risk factors, lipid profile and statins, RA patients showed lower PCSK9 serum concentrations than controls (beta coefficient -45 95%CI [-53, -38] ng/ml, p=0.00). PCSK9 was associated with both cIMT and the presence of carotid plaques in RA patients. However, this association was lost after adjusting for classical cardiovascular risk factors. CONCLUSIONS: PCSK9 is down-regulated in patients with RA.


Assuntos
Artrite Reumatoide/sangue , Doenças das Artérias Carótidas/sangue , Placa Aterosclerótica/sangue , Pró-Proteína Convertase 9/sangue , Regulação para Cima , Idoso , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico por imagem , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos Transversais , Feminino , Humanos , Lipídeos/sangue , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem
14.
Sci Rep ; 6: 31979, 2016 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-27534721

RESUMO

Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan. Subclinical atherosclerosis was determined in 1,298 of them by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques). CRP serum levels at diagnosis and at the time of carotid ultrasonography were measured in 1,662 and 1,193 patients, respectively, by immunoturbidimetry. Interestingly, a relationship between CRP and CRP serum levels at diagnosis and at the time of the carotid ultrasonography was disclosed. However, no statistically significant differences were found when CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were evaluated according to the presence/absence of CV events, carotid plaques and cIMT after adjustment. Our results do not confirm an association between these genes and CV disease in RA.


Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/genética , Aterosclerose/sangue , Aterosclerose/genética , Proteína C-Reativa/genética , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , Idoso , Artrite Reumatoide/epidemiologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/epidemiologia , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Grupo com Ancestrais do Continente Europeu , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco
15.
Autoimmun Rev ; 15(11): 1013-1030, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27490206

RESUMO

Cardiovascular disease (CV) is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). This is the result of an accelerated atherosclerotic process. Adequate CV risk stratification has special relevance in RA to identify patients at risk of CV disease. However, current CV risk screening and management strategies underestimate the actual CV risk in RA. Consequently, the search for additional tools that may help to identify those patients at high CV risk has become a key objective in the last years. In this regard, non-invasive surrogates, such as carotid ultrasonography, have been found to be excellent predictors of future CV events. In addition, several studies have revealed the relevance of a genetic component in the development of CV disease in RA patients. Besides an association with HLA-DRB1* shared epitope alleles other gene polymorphisms located inside and outside the HLA seem to influence the risk of cardiovascular disease in RA. Moreover, serum levels of some metabolic syndrome-related biomarkers, adipokines such as adiponectin and biomarkers of endothelial cell activation and inflammation such as Osteoprotegerin and Asymmetric dimethylarginine have recently been found useful for the prediction of CV disease in these patients. An update of the current knowledge on these potential markers, especially focused on new genetic and serological biomarkers is shown in this review.


Assuntos
Artrite Reumatoide/complicações , Doenças Cardiovasculares/epidemiologia , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/genética , Cadeias HLA-DRB1/genética , Humanos , Mediadores da Inflamação/sangue , Medição de Risco , Fatores de Risco
16.
Sci Rep ; 6: 29713, 2016 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-27403809

RESUMO

Osteoprotegerin (OPG), receptor activator of nuclear factor-ΚB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been involved in rheumatoid arthritis (RA) pathophysiology. In this study, we assessed messenger RNA (mRNA) expression of these molecules by qPCR in peripheral blood from 26 patients with RA (12 of them with ischemic heart disease -IHD) and 10 healthy controls. Correlation coefficients between OPG, RANKL and TRAIL expression levels in RA patients and their clinical and demographic characteristics were also evaluated. Whereas OPG and OPG/TRAIL ratio expression were significantly increased in RA patients compared to controls (fold change = 1.79, p = 0.013 and 2.07, p = 0.030, respectively), RANKL/OPG ratio was significantly decreased (fold change = 0.50, p = 0.020). No significant differences were found between patients and controls in RANKL and TRAIL expression. Interestingly, TRAIL expression was significantly higher in RA patients with IHD compared to those without IHD (fold change = 1.46, p = 0.033). Moreover, biologic disease-modifying antirheumatic drugs (DMARDs) significantly decreased RANKL expression in RA patients (p = 0.016). Our study supports an important role of OPG and TRAIL in RA. Furthermore, it highlights an effect of biologic DMARDs in the modulation of RANKL.


Assuntos
Artrite Reumatoide/sangue , Regulação da Expressão Gênica , Osteoprotegerina/sangue , Ligante RANK/sangue , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Feminino , Humanos , Masculino , Isquemia Miocárdica/sangue , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/patologia
17.
Clin Exp Rheumatol ; 34(3 Suppl 97): S84-8, 2016 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26842496

RESUMO

OBJECTIVES: Data from a small series suggested that the Interleukin 1 beta (IL1ß) rs16944 polymorphism may be associated with severe renal involvement and persistent renal damage (renal sequelae) in Henoch-Schönlein purpura (HSP). To confirm this association, we assessed the largest cohort of Caucasian HSP patients ever considered for genetic studies. METHODS: 338 Spanish HSP patients and 635 sex and ethnically matched controls were recruited in this study. All patients were required to have had at least 6 months' follow-up. Patients and controls were genotyped for IL1ß rs16944 by TaqMan genotyping assay. RESULTS: No differences between IL1ß rs16944 genotype or allele frequencies were found either in the case/control study or when HSP patients were stratified according to the age at disease onset, presence of nephritis or gastrointestinal manifestations. Nevertheless, 4 (25%) of the 16 HSP patients who developed severe renal manifestations carried the TT genotype versus 29 (9%) of 322 who did not develop this complication (p=0.01, OR=5.48, 95% CI: 1.01-28.10). Accordingly, patients carrying the mutant T allele had an increased risk of developing severe nephropathy (p=0.016, OR=2.35, 95% CI: 1.09-5.07). Additionally, a significant increase of the TT genotype was observed in patients with persistent renal damage when compared with those patients without this complication (25% versus 8.6%, respectively; p=0.0035, OR=4.90, 95% CI: 1.26- 18.51). Moreover, renal sequelae were more common in patients carrying the mutant T allele (p=0.0076, OR=2.20, 95% CI: 1.17-4.14). CONCLUSIONS: Our results support that the IL1ß rs16944 polymorphism may be a potential marker of severe renal manifestations and renal sequelae in HSP.


Assuntos
Interleucina-1beta/genética , Nefropatias/etiologia , Polimorfismo de Nucleotídeo Único , Púrpura de Schoenlein-Henoch/genética , Adolescente , Criança , Pré-Escolar , Feminino , Marcadores Genéticos/genética , Genótipo , Humanos , Masculino , Púrpura de Schoenlein-Henoch/complicações
18.
Clin Exp Rheumatol ; 34(1): 106-10, 2016 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26843177

RESUMO

OBJECTIVES: Impairment of methylene tetrahydrofolate reductase (MTHFR), a key enzyme in the folate metabolism, results in an elevated plasma level of homocysteine, considered an independent risk factor for cardiovascular (CV) disease. Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased risk of CV death. Polymorphisms in the MTHFR gene increase the frequency of CV disease in RA. The aim of this study was to determine the expression of MTHFR gene in patients with RA, with and without ischaemic heart disease (IHD). METHODS: Relative expression of MTHFR gene and beta-actin and GAPDH as housekeeping genes was quantified by quantitative real-time polymerase chain reaction. It was analysed by the comparative Ct (threshold cycle) method in peripheral blood from 26 Spanish patients with RA (12 with IHD and 14 without IHD) and 10 healthy controls. MTHFR expression level in RA patients was also assessed according to disease activity, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies status. RESULTS: MTHFR expression was significantly reduced in patients with RA compared to controls (fold change = 0.85, p=0.029). It was especially true for RA patients with IHD (fold change= 0.79, p=0.021). However, no statistically significant relationship between MTHFR expression level in patients with RA and DAS28 CRP, DAS28 ESR, RF and anti-CCP status was observed. CONCLUSIONS: Patients with RA, in particular those with IHD, show a decreased expression of the MTHFR gene. This may support a potential implication of the transcriptional regulation of MTHFR in the pathogenesis of RA.


Assuntos
Artrite Reumatoide/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/enzimologia , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/sangue , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/enzimologia , Peptídeos Cíclicos/imunologia , RNA Mensageiro/sangue , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Fator Reumatoide/sangue , Índice de Gravidade de Doença , Espanha
19.
Bonekey Rep ; 5: 775, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26909149

RESUMO

Systemic autoimmune diseases (SADs) are associated with lower bone mass and an increased risk of fractures. Sclerostin has a pivotal role in bone metabolism. Available data on circulating sclerostin levels in healthy subjects are limited, whereas those in SAD patients are absent. Our objective was to determine circulating sclerostin concentrations in systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Crohn's disease (CD) patients, and to analyze the factors associated with sclerostin concentrations. In this cross-sectional case-control study, serum sclerostin levels were measured in 38 SLE patients, 20 CD patients, 8 SSc patients and 20 healthy controls using a sclerostin ELISA. The mean values of the sclerostin (95% confidence interval) were 35.36 pmol l(-1) (12-101) in patients and 33.92 pmol l(-1) (2.31-100) in control subjects. The mean sclerostin value was 36.4 pmol l(-1) (22.1-48.5) in SLE patients, 26.7 pmol l(-1) (17.3-36.3) in CD patients and 51.8 pmol l(-1) (26.5-77.1) in SSc patients (P=0.001). Serum sclerostin levels were positively correlated with age (P<0.001), body mass index (BMI) (P=0.01) and lumbar spine Z-score (P=0.001) and negatively with creatinine clearance (P=0.001). Glucocorticoid treatment did not affect sclerostin levels. Sclerostin levels seem to have a heterogeneous pattern in different autoimmune diseases. SLE and SSc patients did not differ from healthy controls regarding sclerostin levels. The CD group had significantly lower values compared with SSc patients. Factors associated with sclerostin levels in autoimmune diseases seem to be the same than in the general population.

20.
Atherosclerosis ; 245: 139-42, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26724524

RESUMO

INTRODUCTION: An association between the vitamin D receptor (VDR) GAT haplotype and coronary artery disease (CAD) in type-2 diabetes has recently been described. Since cardiovascular mortality in rheumatoid arthritis (RA) is comparable to that observed for patients with type-2 diabetes, we aimed to determine if VDR GAT haplotype is also associated with atherosclerotic disease in RA. MATERIAL AND METHODS: 591 Northern Spanish RA patients were genotyped for 4 VDR polymorphisms (rs731236 A/G; rs7975232 A/C; rs1544410C/T; rs2228570 G/A). Atherosclerotic disease was established by the presence of carotid plaques in carotid ultrasound. RESULTS: VDR rs7975232 AA genotype was increased in RA patients with plaques (p = 0.045, OR = 1.46 [1.01-2.18]). More importantly, the frequency of carotid plaques was significantly increased in RA patients who carried the GATG haplotype (p = 0.009, OR = 1.56 [1.09-2.42]). CONCLUSION: Our results suggest a potential VDR GATG haplotype association with atherosclerotic disease in RA patients.


Assuntos
Artrite Reumatoide/genética , Aterosclerose/genética , DNA/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Alelos , Artrite Reumatoide/complicações , Artrite Reumatoide/metabolismo , Aterosclerose/etiologia , Aterosclerose/metabolismo , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Calcitriol/metabolismo , Estudos Retrospectivos
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