RESUMO
BACKGROUND: Retinol-binding protein-4 (RBP4), an adipokine considered as an emerging cardiometabolic risk factor, is increased in patients with moderate-to-severe psoriasis. OBJECTIVE: In this study, we aimed to establish the effect of anti-TNF-α therapy on RBP4 levels in patients with moderate-to-severe psoriasis. We also assessed if RBP4 levels correlate with metabolic syndrome features and disease severity in these patients. METHODS: Prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with adalimumab. Patients with kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of treatment (time 0) and at month 6. RESULTS: Twenty-nine patients were assessed. Statistically significant reduction (P = 0.0001) of RBP4 levels was observed after 6 months of therapy (RBP4 at time 0: 55.7 ± 21.4 µg/mL, vs. 35.6 ± 29.9 µg/mL at month 6). No significant correlation between basal RBP4 levels and metabolic syndrome features or disease severity was found. Nevertheless, although RBP4 levels did not correlate with insulin resistance, a negative and significant correlation between RBP4 levels obtained after 6 months of adalimumab therapy and other metabolic syndrome features such as abdominal perimeter and body mass index were observed. At that time, a negative and significant correlation between RBP4 levels and disease activity scores and ultrasensitive CRP levels was also disclosed. CONCLUSION: Our results support an influence of the anti-TNF-α blockade on RBP4 serum levels. This finding is of potential relevance due to increased risk of cardiovascular disease in patients with psoriasis.
Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Psoríase/tratamento farmacológico , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Feminino , Humanos , Masculino , Estudos Prospectivos , Psoríase/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: Altered secretion patterns of proinflammatory adipokines may influence the increased risk of cardiovascular mortality observed in patients with chronic inflammatory diseases. OBJECTIVE: To determine whether two adipokines, leptin and resistin, correlate with metabolic syndrome features and disease severity in psoriatic patients who underwent anti-TNF-α therapy. METHODS: Prospective study of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α- adalimumab. Patients with kidney disease, hypertension or body mass index ≥35 Kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of anti-TNF-α treatment and at month 6. RESULTS: Twenty-nine patients were assessed. A correlation between adiposity and leptin was observed (waist circumference and leptin levels after 6 months of therapy: r = 0.43; P = 0.030). Leptin concentration also correlated with blood pressure before adalimumab onset (systolic: r = 0.48; P = 0.013 and diastolic blood pressure: r = 0.50; P = 0.010 ). A marginally significant negative correlation between insulin sensitivity (QUICKI) and leptin levels was also observed. CRP levels correlated with leptin prior to the onset of adalimumab (r = 0.45; P = 0.020) and with resistin both before (r = 0.45; P = 0.020) and after 6 months of therapy (r = 0.55; P = 0.004). A positive association between parameters of disease activity such as BSA (r = 0.60; P = 0.001) and PASI (r = 0.63; P = 0.001) prior to the onset of adalimumab therapy and resistin concentrations was also disclosed. No significant changes in leptin and resistin concentrations following the 6-month treatment with adalimumab were seen. CONCLUSION: In patients with moderate-to-severe psoriasis leptin correlates with metabolic syndrome features and inflammation whereas resistin correlate with inflammation and disease severity.
Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Leptina/sangue , Psoríase/sangue , Psoríase/tratamento farmacológico , Resistina/sangue , Adiposidade , Adulto , Pressão Sanguínea , Superfície Corporal , Proteína C-Reativa/metabolismo , Feminino , Humanos , Inflamação/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Estudos Prospectivos , Psoríase/complicações , Índice de Gravidade de Doença , Fatores Sexuais , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Circunferência da CinturaRESUMO
OBJECTIVE: Psoriasis is a chronic inflammatory disease associated with increased risk of cardiovascular death. Several studies have shown a beneficial effect of anti-TNF-α therapy on the mechanisms associated with accelerated atherogenesis in patients with inflammatory arthritis, including an improvement of insulin sensitivity. In this study, we aimed to determine for the first time whether the anti-TNF-α monoclonal antibody adalimumab may improve insulin sensitivity in non-diabetic patients with psoriasis. METHODS: Prospective study on a series of consecutive non-diabetic patients with moderate to severe psoriasis seen at the Dermatology Division of Hospital Universitario Marques de Valdecilla (Northern Spain) who completed 6 months of therapy with adalimumab (80 mg at week 0 followed by 40 mg every other week, starting 1 week after the initial dose). Patients with chronic kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation including assessment of insulin sensitivity using the Quantitative Insulin Sensitivity Check Index (QUICKI) was performed at the onset of the treatment (time 0) and at month 6. RESULTS: Twenty-nine patients (52% women; 38.6 ± 10.7 years) with moderate to severe psoriasis [body surface area (BSA) 37.9 ± 16.3%], Psoriasis Area and Severity Index [(PASI) 18.9 ± 7.8] were assessed. Statistically significant improvement (P=0.008) of insulin sensitivity was observed after 6 months of adalimumab therapy (QUICKI at time 0: 0.35 ± 0.04 vs. 0.37 ± 0.04 at month 6). Significant improvement of erythrocyte sedimentation rate, ultrasensitive C-reactive protein, BSA, PASI, Nail Psoriasis Severity Index, physician global assessment and psoriatic arthritis screening and evaluation questionnaire was also observed at month 6 (P < 0.05 for each variable). CONCLUSION: Our results support a beneficial effect of the anti-TNF-α blockade on the mechanisms associated with accelerated atherogenesis in patients with psoriasis.
Assuntos
Adalimumab/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Imunoterapia/métodos , Resistência à Insulina , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anti-Inflamatórios/administração & dosagem , Diabetes Mellitus , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Masculino , Estudos Prospectivos , Psoríase/imunologia , Psoríase/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To determine whether circulating osteopontin (OPN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are increased compared with controls and to establish whether disease activity, systemic inflammation, metabolic syndrome, adipokines and biomarkers of atherosclerosis are potential determinants of circulating OPN levels in these patients. METHODS: We assessed OPN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. OPN levels were measured immediately before and after an infliximab infusion, at time 0 and at time 120 minutes respectively. Correlations of OPN serum levels with clinical features, disease activity, systemic inflammation, metabolic syndrome and several biomarkers of atherosclerosis were assessed. Potential changes in OPN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: At the time of the study AS patients undergoing anti-TNF-α therapy had low disease activity (mean BASDAI 2.94) and they showed similar OPN serum levels to healthy controls. No differences in OPN levels according to the specific clinical features of the disease were seen. Also, no correlation between OPN concentration and insulin resistance and adipokines was observed. However, a positive correlation between OPN and angiopoietin-2 (Angpt-2) serum levels was found (r=0.397; p=0.04). In addition, a single infliximab infusion led to a marginal statistically significant reduction in OPN levels (24112.19±14608.73 pg/ml at time 0 versus 21806.62±11390.83 pg/ml at time 120'; p=0.05). CONCLUSIONS: OPN and Angpt-2 serum levels are correlated in non-diabetic AS patients undergoing TNF-α antagonist therapy.
Assuntos
Angiopoietina-2/sangue , Anticorpos Monoclonais , Aterosclerose , Osteopontina/sangue , Espondilite Anquilosante , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Aterosclerose/metabolismo , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Infliximab , Masculino , Metabolismo/efeitos dos fármacos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Fatores de Risco , Espanha , Espondilite Anquilosante/complicações , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/metabolismo , Estatística como Assunto , Resultado do TratamentoAssuntos
Artrite/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Sarcoidose/genética , Feminino , Humanos , MasculinoRESUMO
OBJECTIVES: To determine whether circulating gelsolin (GSN) levels in patients with ankylosing spondylitis (AS) undergoing TNF-α antagonist-infliximab-therapy are altered compared with controls and to establish whether disease activity, systemic inflammation and metabolic syndrome are potential determinants of circulating GSN levels in these patients. METHODS: We assessed GSN serum concentrations in a series of 30 non-diabetic AS patients without cardiovascular (CV) disease undergoing TNF-α antagonist-infliximab therapy and 48 matched controls. GSN levels were measured immediately before and after an infliximab infusion. Correlations of GSN serum levels with disease activity, systemic inflammation and metabolic syndrome were assessed. Potential changes in GSN concentration following an infusion of anti-TNF-α monoclonal antibody-infliximab were also analysed. RESULTS: Although at the time of the study AS patients undergoing anti-TNF-α therapy had adequate control of the disease (mean BASDAI 2.94), they showed lower GSN serum levels than healthy controls (mean±SD: 38660.42±23624.6 ng/ml versus 68975.43±31246.79 ng/ml; p<0.0001). When AS patients were stratified according to sex, we observed that GSN levels were significantly lower in men than in women (p=0.032). However, no differences in GSN levels according to the specific clinical features of the disease were seen. No association was found between GSN concentration and adipokines or biomarkers of endothelial cell activation. However, correlation between basal GSN levels and insulin resistance was observed. A single infliximab infusion did not lead to significant changes in GSN levels. CONCLUSIONS: GSN concentration is reduced in AS patients undergoing periodical anti-TNF-α therapy and low disease activity. Potential association with some metabolic syndrome features seems to exist.
Assuntos
Anticorpos Monoclonais , Gelsolina/metabolismo , Espondilite Anquilosante , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adipocinas/metabolismo , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Humanos , Inflamação/tratamento farmacológico , Infliximab , Infusões Intravenosas , Masculino , Metabolismo/efeitos dos fármacos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Gravidade do Paciente , Fatores Sexuais , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/metabolismo , Espondilite Anquilosante/fisiopatologia , Estatística como Assunto , Resultado do TratamentoRESUMO
Rheumatoid arthritis (RA) is an inflammatory disease associated with high risk of cardiovascular (CV) events. Recently, the rs964184 polymorphism has been associated with coronary artery disease in nonrheumatic Caucasian individuals. 2160 Spanish RA patients were genotyped for the rs964184 polymorphism. Sex, age at diagnosis and traditional CV risk factors (diabetes mellitus, dyslipidemia and smoking habit) were associated with increased risk of CV events. Interestingly, RA patients carrying the rs964184 GG genotype had significantly higher risk of CV events than those with CC genotype [hazard ratio (HR) = 2.91, 95% confidence interval (CI): 1.36-6.26, P = 0.006] after adjusting the results for sex, age at diagnosis and traditional CV risk factors. Our results indicate that rs964184 polymorphism is associated with CV disease in RA.
Assuntos
Artrite Reumatoide/complicações , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/genética , Cromossomos Humanos Par 11/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Artrite Reumatoide/genética , Demografia , Feminino , Genoma Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Rheumatoid arthritis (RA) is a chronic polygenic inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular disease (CVD). In this study, we evaluated the potential association of 9p21.3 single-nucleotide polymorphisms (SNPs) - previously linked to coronary artery disease - and CVD risk in 2001 Spanish RA patients genotyped for 9p21.3 SNPs using TaqMan™ assays. Carotid intima media thickness (cIMT) and presence of carotid plaques were also analyzed. Cox regression model did not disclose significant differences between patients who experienced CVD and those who did not. Neither association was found between cIMT or carotid plaques and SNPs allele distribution. In conclusion, results do not support a role of rs10116277 or rs1537375 SNPs in CVD risk in Spanish RA patients.
Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Doenças Cardiovasculares/genética , Loci Gênicos/genética , Predisposição Genética para Doença , Adulto , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/imunologia , Artérias Carótidas/patologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco , EspanhaRESUMO
Henoch-Schönlein purpura (HSP) is the most common type of primary small-sized blood vessel vasculitis in children and an uncommon condition in adults. Interleukin (IL)-6 is a proinflammatory cytokine whose effect is controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/gp130) is the signal-transducing subunit of the IL-6R. Two hundred and eighty five Spanish HSP patients and 877 sex and ethnically matched controls were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional polymorphisms. No significant differences in the genotype and allele frequencies between HSP patients and controls were observed. Moreover, there were no differences between HSP patients according to the age at disease onset, presence of nephritis or gastrointestinal manifestations. Our results do not confirm association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with HSP.
Assuntos
Receptor gp130 de Citocina/genética , Predisposição Genética para Doença , Vasculite por IgA/genética , Receptores de Interleucina-6/genética , Adulto , Criança , Progressão da Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Vasculite por IgA/imunologia , Masculino , Polimorfismo Genético , EspanhaRESUMO
OBJECTIVE: The methionine sulfoxide reductase A (MSRA) gene is related to oxidative stress that has been involved in the susceptibility to rheumatoid arthritis (RA) in genome-wide pathway analysis and replication studies. The aim of the present study was to determine whether the MSRA gene is implicated in susceptibility to cardiovascular (CV) disease in RA patients. METHODS: A total of 1302 patients fulfilling the 1987 American College of Rheumatism classification criteria for RA were genotyped for the MSRA rs10903323 (G/A) polymorphism. Two hundred and thirty-three (17.9%) patients experienced CV events. Human leucocyte antigen (HLA)-DRB1 genotyping was performed using molecular-based methods. Multiple logistic regression models were constructed with adjustments for gender, age at RA diagnosis, follow-up, rheumatoid shared epitope, and traditional CV risk as potential confounders. RESULTS: There were no statistically significant differences in the allele or genotype frequencies for the MSRA rs10903323 polymorphism between RA patients who experienced CV events and those who did not. However, an adjusted logistic regression model disclosed that the minor allele G yielded a marginally significant increased risk of CV events in this series of patients with RA [p = 0.05, odds ratio (OR) 1.68, 95% confidence interval (CI) 1.00-2.85]. When the logistic regression model was adjusted for anti-cyclic citrullinated peptide (anti-CCP) antibody status instead of for shared epitope, an increased risk of having ischaemic heart disease was found in patients carrying the minor allele G (p = 0.04, OR 2.00, 95% CI 1.03-3.88). CONCLUSION: The MSRA rs10903323 gene polymorphism may be implicated in the increased risk to develop CV events, in particular ischaemic heart disease, observed in RA patients.
Assuntos
Artrite Reumatoide/genética , Doenças Cardiovasculares/genética , Predisposição Genética para Doença , Metionina Sulfóxido Redutases/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Artrite Reumatoide/complicações , Doenças Cardiovasculares/complicações , Epitopos/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVES: MHCIITA is a major regulator of MHC expression that has been reported to be involved in the susceptibility to rheumatoid arthritis (RA) and myocardial infarction. In this study we investigated the potential association of two MHCIITA gene polymorphisms with cardiovascular (CV) risk in patients with RA. METHODS: 1302 patients fulfilling the 1987 ACR classification criteria for RA were genotyped for the MHCIITA rs3087456 and rs4774 gene polymorphisms to determine the influence of MHCIITA variants in the development of CV events. The potential influence of these polymorphisms in the development of subclinical atherosclerosis was also analysed in a subgroup of patients with no history of CV events by the assessment of two surrogate markers of atherosclerosis; brachial and carotid ultrasonography to determine endothelial function and carotid artery intima-media thickness, respectively. RESULTS: No statistically significant differences in the allele or genotype frequencies for each individual MHCIITA gene polymorphism between RA patients who experienced CV events, or not, were found. This was also the case when each polymorphism was assessed according to results obtained from surrogate markers of atherosclerosis. Also, in assessing the combined influence of both MHCIITA gene polymorphisms in the risk of CV disease after adjustment for gender, age at time of disease diagnosis, follow-up time, traditional CV risk factors, and shared epitope status, patients with CV events only showed a marginally decreased frequency of the MHCIITA rs3087456-rs4774 G-G allele combination (p=0.08; odds ratio: 0.63 [95% confidence interval: 0.37-1.05]). CONCLUSIONS: Our data do not support an influence of MHCIITA rs3087456 and rs4774 polymorphisms in the increased risk of CV events of patients with RA.
Assuntos
Artrite Reumatoide/genética , Doenças Cardiovasculares/genética , Predisposição Genética para Doença , Proteínas Nucleares/genética , Transativadores/genética , Adulto , Idoso , Artrite Reumatoide/complicações , Doenças Cardiovasculares/complicações , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Interleukin-6 (IL-6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/ gp130) is the signal transducing subunit of the IL-6R. We assessed the influence of the IL6R and the IL6ST/gp130 genes in the risk of cardiovascular (CV) disease in RA. For this purpose, 1250 Spanish patients with RA were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional gene polymorphisms. Patients were stratified according to the presence or absence of CV events. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using two surrogate markers of atherosclerosis (flow-mediated endothelium-dependent vasodilatation and carotid intima-media thickness). No significant differences in the genotype and allele frequencies for both gene polymorphisms between patients with and without CV events were observed. It was also the case when values of surrogate markers of atherosclerosis were compared according to IL6R and IL6ST genotype frequencies. In conclusion, our results do not confirm an association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with CV disease in RA.
Assuntos
Artrite Reumatoide/genética , Aterosclerose/genética , Receptor gp130 de Citocina/genética , Polimorfismo Genético , Receptores de Interleucina-6/genética , Adulto , Alelos , Artrite Reumatoide/complicações , Aterosclerose/complicações , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , EspanhaRESUMO
Mutations in the TNFRSF13B (TACI) gene have been associated with common variable immunodeficiency, and a role in immunoglobulin A deficiency (IgAD) has also been suggested. We aimed at studying the role of several polymorphisms along this gene in IgAD susceptibility. Three TNFRSF13B mutations (C104R, A181E and R202H) and eight additional single nucleotide polymorphisms in the gene were genotyped in 338 Spanish IgAD patients and 553 ethnically matched healthy controls and tested for association. Data from parents of 114 IgAD patients were also collected and used for additional analysis. No statistically significant differences were observed after comparing patients and controls for any single nucleotide polymorphism analysed. Therefore, our work seems to discard a role of TNFRSF13B mutations in IgAD, concordantly with the most recent published studies.