Disminución de los niveles plasmáticos de clusterina en pacientes con psoriasis / Decreased Plasma Levels of Clusterin in Patients With Psoriasis

Introducción y objetivos: La psoriasis es una enfermedad inflamatoria crónica que se ha asociado a un incremento del riesgo cardiovascular. La clusterina (apolipoproteína J) es un componente de las lipoproteínas de alta densidad (HDL) y tiene un papel protector de la ateroesclerosis. El objetivo del estudio ha sido evaluar la clusterina y el factor inhibitorio de la migración del macrófago (MIF) plasmáticos en pacientes con psoriasis grave comparando grupos de pacientes con distintos riesgos cardiovasculares asociados. Material y métodos: Se estudiaron 21 pacientes con psoriasis grave (Psoriasis Area Severity Index [PASI] y Body Surface Area [BSA] > 10) y 11 controles sin enfermedad dermatológica. Se evaluaron los factores de riesgo cardiovascular según criterios del síndrome metabólico del Adult Treatment Panel III (ATP- III ) y la ateromatosis carotídea subclínica mediante ecografía doppler de carótidas. La clusterina y MIF plasmáticos se midieron mediante Enzyme-Linked Immuno Sorbent Assay (ELISA). Resultados: El 47% de los pacientes con psoriasis presentaba criterios de síndrome metabólico y el 33% presentó placa de ateroma carotídea. Se observó una disminución significativa de la clusterina plasmática (μg/ml) en pacientes con psoriasis respecto a controles (81,39 ± 27,30; n = 21, versus 117 ± 21,6, n = 11; p = 0,0017). El MIF plasmático (ng/ml) estaba aumentado significativamente en los pacientes con psoriasis y placa de ateroma carotídea respecto a los controles (53,22 ± 29,02; n = 6, versus 34,21 ± 9,65; n = 11; p = 0,0394). Conclusiones: La disminución de clusterina en pacientes con psoriasis sugiere una relación con la enfermedad y con la situación inflamatoria sistémica. El aumento de MIF en pacientes parece relacionarse con la presencia de factores de riesgo cardiovascular asociados y placa de ateroma carotídea (AU)

Introduction and objectives: Psoriasis is a chronic inflammatory disease that has been linked to increased cardiovascular risk. The glycoprotein clusterin (apolipoprotein J) is a component of high-density lipoproteins and has a protective role in atherosclerosis. The aim of the present study was to evaluate the plasma levels of clusterin and the proinflammatory cytokine macrophage migration inhibitory factor (MIF) in patients with severe psoriasis, comparing groups of patients with different risks of cardiovascular disease. Material and methods: Twenty-one patients with severe psoriasis (psoriasis area severity index and body surface area > 10) and 11 healthy controls with no dermatologic disease were studied. Cardiovascular risk factors were assessed according to the Adult Treatment Panel (ATP) IIIcriteria. Subclinical carotid atheromatosis was assessed by Doppler ultrasonography of the carotid arteries. Plasma clusterin and MIF levels were measured by enzyme-linked immunosorbent assay. Results: ATP-III criteria for metabolic syndrome were met by 47% of the patients, and 33% had carotid atheromatous plaque. Mean (SD) clusterin plasma levels were significantly lower in patients with psoriasis compared with controls (81.39 [27.30] micreg/mL for the 21 patients vs 117[21.6] g/mL for the 11 controls; P = .0017). MIF plasma levels (ng/ml) were significantly higherin patients with atheromatous plaque compared with controls (53.22 [29.02] for the 6 patientswith plaque vs 34.21 [9.65] for the 11 controls; P = 0.0394).Conclusions: The decreased plasma levels of clusterin in psoriatic patients suggested an association with the disease and might be an indicator of systemic inflammatory activity. Increased levels of MIF appear to be associated with cardiovascular risk factors and carotid atheromatous plaque (AU)

Increased gene expression of Toll-like receptor 4 on peripheral blood mononuclear cells in patients with psoriasis.

BACKGROUND: A role for the innate immune system in driving the autoimmune T cell cascade in psoriasis has been proposed. Toll-like receptors-(TLR)-2 and -4 play a role in inflammation, atherosclerosis, and their specific role in psoriasis remains unclear. OBJECTIVE: To evaluate TLR2 and TLR4 gene expression levels in peripheral blood mononuclear cells from psoriatic patients. METHODS: Changes in TLR2 / 4 gene expressions were evaluated using quantitative real-time reverse transcription polymerase chain reaction in peripheral blood mononuclear cells, from twenty-one patients with severe psoriasis, and analysed whether there was any correlation with cytokine plasma levels (T-helper 0-, T-helper 1-, T-helper 2- or regulatory T cells-type), or Calprotectin and with S100A8 and S100A9 gene expression levels. Eleven non-psoriatic healthy controls were analysed. RESULTS: A clear increase in TLR4 gene expression was observed (3.84 ± 0.93, n = 21) together with a moderate increase in TLR2 expression (1.522 ± 0.31, n = 21). Both TLR4 and TLR2 gene expressions were significantly augmented in psoriatic patients compared with controls (all P < 0.001). Correlations between TLR2 and S100A9 gene expressions (r = 0.5145, P = 0.0170, n = 21); and between TLR2 expression and plasma interleukin-2 (r = 0.5667, P = 0.0074); interleukin-4 (r = 0.4766, P = 0.0289), interleukin-10 (r = 0.4355, P = 0.0484) and interleukin-13 (r = 0.4603, P = 0.0358), were found. When patients with atheroma plaque were considered (n = 7), both TLR4 (3.47 ± 0.99, P = 0.0156) and TLR2 (1.63 ± 0.31, P = 0.0156) expressions were significantly increased vs. controls and correlated with plasma TNF-a (r = 0.8929, P = 0.0123, in both cases). CONCLUSION: Differential TLR4 / 2 gene expressions on psoriatic peripheral blood mononuclear cells and correlations with regulatory and / or proinflammatory cytokines and / or damage-associated molecular pattern molecule S100A9 emphasize innate immune response role in psoriasis.

Decreased plasma levels of clusterin in patients with psoriasis.

INTRODUCTION AND OBJECTIVES: Psoriasis is a chronic inflammatory disease that has been linked to increased cardiovascular risk. The glycoprotein clusterin (apolipoprotein J) is a component of high-density lipoproteins and has a protective role in atherosclerosis. The aim of the present study was to evaluate the plasma levels of clusterin and the proinflammatory cytokine macrophage migration inhibitory factor (MIF) in patients with severe psoriasis, comparing groups of patients with different risks of cardiovascular disease. MATERIAL AND METHODS: Twenty-one patients with severe psoriasis (psoriasis area severity index and body surface area>10) and 11 healthy controls with no dermatologic disease were studied. Cardiovascular risk factors were assessed according to the Adult Treatment Panel (ATP) III criteria. Subclinical carotid atheromatosis was assessed by Doppler ultrasonography of the carotid arteries. Plasma clusterin and MIF levels were measured by enzyme-linked immunosorbent assay. RESULTS: ATP-III criteria for metabolic syndrome were met by 47% of the patients, and 33% had carotid atheromatous plaque. Mean (SD) clusterin plasma levels were significantly lower in patients with psoriasis compared with controls (81.39 [27.30] µg/mL for the 21 patients vs 117 [21.6] µg/mL for the 11 controls; P=.0017). MIF plasma levels (ng/ml) were significantly higher in patients with atheromatous plaque compared with controls (53.22 [29.02] for the 6 patients with plaque vs 34.21 [9.65] for the 11 controls; P=.0394). CONCLUSIONS: The decreased plasma levels of clusterin in psoriatic patients suggested an association with the disease and might be an indicator of systemic inflammatory activity. Increased levels of MIF appear to be associated with cardiovascular risk factors and carotid atheromatous plaque.