ANALYSIS OF PARAOXONASE ACTIVITY AND LIPID PROFILE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Background: Immune-inflammatory processes play important role in the pathogenesis and progression of atherosclerosis. Therefore, increasing attention is focused on rheumatic diseases with chronic inflammation, such as systemic lupus erythematosus (SLE). Dyslipidemia and excessive lipid peroxidation are major factors of atherosclerosis in SLE.Objectives: To determine lipid-profile, paraoxonase (PON) and arylesterase activities in 37 lupus patients and 30 age/sex matched normal controls. Association was analysed between these parameters and CRP level, SLEDAI, anti-oxLDL level, dose of corticosteroid and atherothrombotic clinical events, such as coronary heart disease and stroke.Methods: Patients met the ACR criteria for SLE diagnosis. Their age was 40.8±13.9 year, follow-up time 6.7±6.2 year, SLEDAI 2.8±3.4. Lipid parameters were determined by an autoanalyser. PON and arylesterase activities were measured spectrophotometrically using paraoxon and phenylacetate as substrate, respectively. Phenotypic distribution of PON was determined by the dual substrate method. Anti-oxLDL was determined by an ELISA method, CRP was measured by automatised immunoassay. Statistical analysis was performed by SPSS program.Results: PON activity (121.9±65.9 U/mL) reduced significantly (p<0.001) in SLE as compared to control (188.1±78.9U/mL). Although, PON activity decreased by increasing age, CRP and anti-oxLDL levels, no significant correlation was found between PON activity and SLEDAI, dose of corticosteroid therapy, CRP and anti-oxLDL level. Reduced PON activity correlated with the presence of clinical atherothrombotic complications (p=0.009). There was no high activity BB phenotype shown in SLE patients. Arylesterase activity did not differ in SLE and control groups. Lipid parameters (total cholesterol, LDL-C, HDL-C, Apo-AI and ApoB) were within normal range in both groups. Total cholesterol and LDL-C levels were in correlation with disease duration in SLE patients (p<0.05).Conclusion: We found decreased paraoxonase activity in patients with systemic lupus erythematosus despite of long disease duration and low inflammatory activity. Lipid parameters and arylesterase activity, which reflects PON content, were normal in lupus patients. This suggests that other mechanisms, such as anti-PON antibodies, genetic factors, difference in distribution HDL-subfractions or enzyme abnormalities in HDL remodelling may stand at the background of reduced paraoxonase activity in SLE.References: 1. Paragh G. et al: Nephron 1998, 80: 166-170.2. Alves J. D. et al: Arthritis Rheum. 2002, 46: 2686-2694.3. Hochberg M.C.: Arthritis Rheum. 1997, 40: 1725.4. Ward M.M.: Arthritis Rheum. 1995, 38: 1492-1499.5. Manzi S.: Rheumatology (Oxford) 2000, 39: 353-359.6. Voetsch B et al.: Stroke 2002, 33: 1459-1464.7. Nakanishi M et al.: J Atheroscler. Thromb. 2003, 10: 337-342.8. Tsuzura S et al.: Metabolism 2004, 53: 297-302.Citation: Ann Rheum Dis, volume 64, supplement III, year 2005, page 225Session: SLE – Etiology and pathogenesis/Animal models