Lege Artis Medicinae

[STUDY OF PARAOXONASE ACTIVITY IN MIXED CONNECTIVE TISSUE DISEASE]

BODOLAY Edit, SERES Ildikó, JAKAB Zsanett, CSÍPŐ István, SZILÁGYI Anna, SZEGEDI Gyula, PARAGH György

OCTOBER 18, 2006

Lege Artis Medicinae - 2006;16(10)

[INTRODUCTION - Mixed connective tissue disease (MCTD) is an inflammatory autoimmune disease with multiple organ involvement. Immune- inflammatory processes play a crucial role in the pathogenesis of atherosclerosis. The connection between inflammatory parameters and atherosclerosis in MCTD has not yet been studied. Lipid abnormality is an important risk factor of atherosclerosis. Among the lipids, HDL is protective, which is in part due to the antioxidant effect of paraoxonase. In this paper, the lipid profiles and paraoxonase activities of MCTD patients were studied and the factors causing abnormalities were investigated. PATIENTS AND METHODS - Thirty-seven patients with MCTD, who had not taken any lipid lowering drugs in the past 2 months, were enrolled in the study. Thirty healthy individuals served as controls. At the time of the study the mean age of the MCTD patients was 51.2 ± 9.5 years, and the mean disease duration was 11.0 ± 7.2 years. Paraoxonase activity was determined by spectrophotometry, lipid profiles were determined by a Cobas Integra 700 Analyser, the von Willebrand factor antigen (vWFAg) was measured by turbidimetry in platelet-poor plasma and the thrombomodulin and anti-endothelial cell antibody (AECA) measurements were carried out by ELISA methods. RESULTS - Paraoxonase activity in the MCTD patients was lower than in the control population (118.5 ± 64.6 U/l vs. 188.0 ± 77.6, p<0.001). The arylesterase activity was also significantly lower in the patients (p<0.001). The reduction of paraoxonase activity was in correlation with the age of the patients, the duration of the disease and with vascular (eye, cardiac, cerebral) disorders. The total cholesterol and triglicerid levels of the patients were significantly increased compared to the control group, while in the apoA1 levels a significant reduction was seen. A very strong correlation was observed between the reduction of paraoxonase activity and the increase of endothelial cell activation markers (thrombomodulin, vWFAg, AECA). There was no difference in the values of patients with or without corticosteroid treatment. CONCLUSIONS - The results suggest that in MCTD there is an increased risk for atherosclerosis. Apart from an elevated cholesterol and triglicerid level, a reduced paraoxonase level and activity may also play a role in the development of atherosclerosis,. Therefore, in patients with MCTD, due to the increased oxidative processes and the impaired elimination of free radicals, a sustained damage to the endothelial cells occurs, which is indicated by increased levels of thrombomodulin, vWFAg, and anti-endothelial antibody.]

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