Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
Mais filtros










Intervalo de ano de publicação
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.
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.

3.
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.

4.
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
5.
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
6.
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.

7.
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.

8.
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
9.
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
10.
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
11.
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
12.
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
13.
Microbes Infect ; 18(9): 559-64, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27235198

RESUMO

The molecular and genetic basis of Acinetobacter baumannii and Acinetobacter pittii virulence remains poorly understood, and there is still lack of knowledge in host cell response to these bacteria. In this study, we have used eleven clinical Acinetobacter strains (A. baumannii n = 5; A. pittii n = 6) to unravel bacterial adherence, invasion and cytotoxicity to human lung epithelial cells. Our results showed that adherence to epithelial cells by Acinetobacter strains is scarce and cellular invasion was not truly detected. In addition, all Acinetobacter strains failed to induce any cytotoxic effect on A549 cells.


Assuntos
Infecções por Acinetobacter/microbiologia , Acinetobacter/fisiologia , Aderência Bacteriana , Células Epiteliais/microbiologia , Pneumonia Bacteriana/microbiologia , Células A549 , Acinetobacter/isolamento & purificação , Sobrevivência Celular , Células Epiteliais/fisiologia , Humanos
14.
J Dermatol ; 43(11): 1267-1272, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27062420

RESUMO

The aim of the present study was to determine if the use of the anti-tumor necrosis factor (TNF)-α monoclonal antibody adalimumab could improve endothelial function and arterial stiffness in patients with moderate to severe psoriasis. This was a prospective study on a series of consecutive patients with moderate to severe psoriasis who completed 6 months of therapy with adalimumab. Patients with history of cardiovascular events, diabetes mellitus, kidney disease, hypertension or body mass index of 35 kg/m2 or more were excluded. Assessment of endothelial function by brachial artery reactivity measuring flow-mediated endothelial dependent vasodilatation (FMD%), and carotid arterial stiffness by pulse wave velocity (PWV) was performed at the onset of treatment (time 0) and at month 6. Twenty-nine patients were studied. Anti-TNF-α adalimumab therapy yielded a significant improvement of endothelial function. The mean ± standard deviation (SD) FMD% values increased from 6.19 ± 2.44% at the onset of adalimumab to 7.46 ± 2.43% after 6 months of treatment with this biologic agent (P = 0.008). Likewise, following the use of adalimumab, PWV levels decreased from 6.28 ± 1.04 m/s at the onset of adalimumab to 5.69 ± 1.31 m/s at 6 months (P = 0.03). In conclusion, patients with moderate to severe psoriasis exhibit improvement of endothelial function and arterial stiffness following anti-TNF-α therapy. These findings are of potential relevance due to increased risk of cardiovascular disease in patients with severe psoriasis.


Assuntos
Adalimumab/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Rigidez Vascular/efeitos dos fármacos , Adalimumab/farmacologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
15.
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
16.
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
17.
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
18.
PLoS One ; 11(1): e0147569, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26800524

RESUMO

Ceftaroline (CPT) is a novel cephalosporin with in vitro activity against Staphylococcus aureus. Ceftaroline exhibits a level of binding affinity for PBPs in S. aureus including PBP2a of methicillin-resistant S. aureus (MRSA). The aims of this study were to investigate the morphological, physiological and molecular responses of MRSA clinical strains and MRSA biofilms to sub-MICs (1/4 and 1/16 MIC) of ceftaroline by using transmission, scanning and confocal microscopy. We have also used quantitative Real-Time PCR to study the effect of sub-MICs of ceftaroline on the expression of the staphylococcal icaA, agrA, sarA and sasF genes in MRSA biofilms. In one set of experiments, ceftaroline was able to inhibit biofilm formation in all strains tested at MIC, however, a strain dependent behavior in presence of sub-MICs of ceftaroline was shown. In a second set of experiments, destruction of preformed biofilms by addition of ceftaroline was evaluated. Ceftaroline was able to inhibit biofilm formation at MIC in all strains tested but not at the sub-MICs. Destruction of preformed biofilms was strain dependent because the biofilm formed by a matrix-producing strain was resistant to a challenge with ceftaroline at MIC, whereas in other strains the biofilm was sensitive. At sub-MICs, the impact of ceftaroline on expression of virulence genes was strain-dependent at 1/4 MIC and no correlation between ceftaroline-enhanced biofilm formation and gene regulation was established at 1/16 MIC. Our findings suggest that sub-MICs of ceftaroline enhance bacterial attachment and biofilm formation by some, but not all, MRSA strains and, therefore, stress the importance of maintaining effective bactericidal concentrations of ceftaroline to fight biofilm-MRSA related infections.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Cefalosporinas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana
19.
PLoS One ; 10(11): e0143153, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26571131

RESUMO

OBJECTIVES: To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US). RESULTS: RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed. CONCLUSIONS: In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA.


Assuntos
Artrite Reumatoide/genética , Aterosclerose/genética , Interleucina-33/genética , Adulto , Idoso , Alelos , Artrite Reumatoide/complicações , Aterosclerose/etiologia , Artérias Carótidas/diagnóstico por imagem , Feminino , Seguimentos , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores Tipo I de Interleucina-1/genética , Risco , Ultrassonografia
20.
Arthritis Res Ther ; 17: 286, 2015 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-26458874

RESUMO

INTRODUCTION: To determine whether the PTPN22 (protein tyrosine phosphatase nonreceptor 22)/CSK (c-src tyrosine kinase) pathway is implicated in the susceptibility and clinical heterogeneity of Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies. METHODS: A set of 329 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al. classification criteria and 515 sex and ethnically matched controls were recruited in this study. Two well-known CSK (CSK rs34933034 and CSK rs1378942) and two functional PTPN22 (PTPN22 rs2476601 (R620W) and PTPN22 rs33996649 (R263Q)) polymorphisms, previously associated with autoimmunity, were genotyped with TaqMan single nucleotide polymorphism (SNP) genotyping assays. RESULTS: No significant differences in the genotype and allele frequencies between HSP patients and controls were observed when the CSK rs34933034, CSK rs1378942, PTPN22 rs2476601 (R620W) and PTPN22 rs33996649 (R263Q) polymorphisms were analyzed independently. In keeping with this observation, no significant differences were found when we assessed these polymorphisms combined conforming haplotypes. In addition, there were no differences in the allele or genotype frequencies when HSP patients were stratified according the age at disease onset, sex, presence of arthralgia/arthritis, nephritis or gastrointestinal manifestations. CONCLUSIONS: Our results do not support association between PTPN22/CSK and HSP.


Assuntos
Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Púrpura de Schoenlein-Henoch/genética , Quinases da Família src/genética , Adulto , Criança , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Espanha
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA