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Resposta humoral contra lipoproteínas de alta densidade em doentes com psoríase / Maria João Figueiroa de Góis Paiva Lopes ; orient. José Delgado Alves

Main Author Lopes, Maria João Figueiroa de Góis Paiva Secondary Author Alves, José Delgado Language Português. Country Portugal. Publication Lisboa : NOVA Medical School, Faculdade de Ciências Médicas, 2017 Description 120 p. : fig. ; 30 cm Dissertation Note or Thesis: Tese de Doutoramento, Medicina, Medicina Clínica, Dermatovenereologia, Universidade Nova de Lisboa
Topical name Psoriasis
High density lipotropteins
Academic Dissertation
Portugal
CDU 616 Classification Medicina
Medicina Clinica
Dermatovenereologi
Online Resources Click here to access the eletronic resource http://hdl.handle.net/10362/27854 List(s) this item appears in: Teses NL
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Monografia Biblioteca NMS|FCM
LOP5 TeseD-2017 Available 20180048NL

Tese de Doutoramento, Medicina, Medicina Clínica, Dermatovenereologia, Universidade Nova de Lisboa

Psoriasis is an immunomediated disease with a prevalence of 2-3%. It is the most prevalent chronic inflammatory disease in humans. Historically it was considered as a disease affecting only the skin, and sometimes the joints. However, in the last decades the association of psoriasis with various comorbidities was recognized. These include type II diabetes, hypertension, dyslipidemia, obesity, anxiety, depression, metabolic syndrome, subclinical atherosclerosis and cardiovascular disease (coronary artery disease and cerebrovascular disease). These comorbidities cause a considerable negative socioeconomical impact as well as loss of quality of life. Despite intensive investigation the causes and mechanisms of such associations are yet to be clarified. Psoriasis is associated with classic risk factors for cardiovascular disease but it is also an independent risk factor. It´s inclusion on the Framingham Risk score would lead to the reassignment of most psoriasis patients to a higher risk class, hence to actual changes in the therapeutic strategies and goals for these patients. The chronic inflammatory and oxidative processes occurring in psoriasis are very similar to those underlying atherosclerosis and are certainly implicated in the pathogenesis of the psoriatic plaques on the skin and the atheroma plaques on the arteries, with a parallel evolution. Our group had previously identified anti-HDL antibodies in autoimmune and non-autoimmune diseases, e.g., lupus erythematosus and type 2 diabetes, and associated these antibodies with a hampered HDL function. This project aimed at investigating the presence of anti-HDL antibodies in patients with psoriasis, suggesting a new mechanistic explanation for the association between psoriasis and atherosclerosis as well as providing potential biomarkers for the assessment of cardiovascular risk in these patients. We enrolled 67 consecutive patients with plaque psoriasis from our outpatient clinic, as well as 50 healthy blood donors with matching age and sex. Epidemiologic and clinical data were recorded. IgM and IgG anti-HDL (aHDL), anti-apolipoprotein A-I (aApoA-I), anti-apolipoprotein E (aApoE) and anti-paraoxonase 1 (aPON1) antibodies as well as vascular adhesion molecules (VCAM-1), Il-6 and TNF-a were assessed by ELISA. The plasma lipid profile was determined by standard enzymatic techniques. Apolipoprotein A-I (ApoA-I) and Apolipoprotein E (ApoE) were measured by immunoturbidimetric assays. Paraoxonase 1 (PON1) activity was assessed by quantification of nitrophenol formation by spectrophotometry. Nitric oxide metabolites (NOx) were measured using the Griess reaction. The biologic activity of the antibodies was assessed in vitro by the blockade of HDL inhibition of VCAM-1 expression on HUVECs previously stimulated with TNF- a. In the psoriasis group we found elevated BMI (p=0.043), hypertension (p=0.005), cardiovascular disease (p=0.07), diabetes (p=0.07) and dyslipidemia (p0.001). Patients with psoriasis had higher titres of IgG (but not IgM) aHDL (p0.001). They also had higher IgG aApoA-I (p=0.001) and aApoE antibodies (p0.001). IgG aHDL antibodies titres directly correlated with aApoA-I antibodies (rS=0.432, p 0.001) and aApoE antibodies (rS=0.339, p0.001). Patients with severe psoriasis, defined as baseline PASI10, had higher IgG aHDL and aApoE titres (p=0.010 and p=0.018, respectively) but there was no association with age or disease duration. There was no statistical difference in aPON1 levels between patients and controls. Regarding apoprotein levels, patients had increased ApoE (p=0.031) and decreased ApoA-I (p0.001) levels. There were no differences in inflammation or oxidation markers. The functional in vitro study performed in HUVECs stimulated with TNF-a, showed that IgG aHDL isolated from patients were capable of blocking the inhibitory effect of HDL on the expression of VCAM-1 in the endothelium. To my knowledge, this is the first report showing the presence of aHDL and aApoA-I antibodies in patients with psoriasis. It is also the first report of aApoE in psoriasis and in human pathology. These antibodies were associated with increased disease severity and they block the anti-inflammatory effect of HDL in vitro, which strongly suggest they may play a role in the pathogenesis of atherosclerosis in psoriasis. They may also fulfil the clinical need for biomarkers of cardiovascular risk associated with psoriasis that would help to stratify patients for future prevention and therapeutic approaches.

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