Background Cytokine-mediated immunity plays a crucial role in the pathogenesis of various autoimmune diseases including systemic lupus erythematosus (SLE). Interleukin 23 (IL-23) may be involved in pathogenesis of SLE. Moreover, recent studies showed that targeting of IL-23 or the IL-23 receptor is a potential therapeutic approach for autoimmune diseases including SLE.
Objectives To evaluate association between serum levels of IL-23 and selected characteristics of the disease in SLE patients.
Methods Study was performed in 94 SLE patients (82 women and 12 men) aged 19-73 years and in 27 age and gender matched controls. Serum IL-23 was measured by ELISA method with R&D Systems tests.
The evaluation of atherosclerotic changes was performed on the basis of: intima-media thickness measurement and the presence of atherosclerotic plaques in carotid and lower extremities arteries with B-mode ultrasound and ankle-brachial index measurement with Doppler ultrasonography. Furthermore, we assessed vascular resistance on the basis of high resistance index measurement from Doppler spectrum of popliteal arteries. Those investigations were performed using HDI 3500 (ATL) with 5-12 MHz linear transducer.
We also took into account classical cardiovascular risk factors (hypertension, dyslipidemia, hyperglycemia, overweight/obesity, smoking, oral contraceptives, positive family history of cardiovascular disease), selected clinical manifestations (cardiovascular, cerebrovascular, lupus nephritis, Raynaud’s phenomenon, livedo reticularis, vasculitis, other thromboembolic complications), profile of autoantibodies (antinuclear, antiphospholipid, anti-neutrophil cytoplasmic, anti-endothelial cell).
Statistical analysis was performed with: chi2Yates, chi2Pearson, rank Spearman correlations tests, logistic regression analysis and multivariate stepwise analysis.
Results Concentrations of IL-23 significantly differed between SLE patients and the controls (p=0,0005). Patients with high levels of IL-23 more frequently developed atherosclerosis showed as the presence of plaques in right common femoral artery and lupus nephritis (OR=10,1; 95%CI:1,2-85,1 and OR=3,2; 95%CI:1,1-9,6 respectively). However, from classical atherosclerotic risk factors only obesity was significantly associated with IL-23 (OR=3,8; 95%CI:1,2-12,3). Immunological characteristics significantly related to IL-23 were anti-phosphatidylethanolamine antibodies, especially of IgG class (OR=12,7; 95%CI:1,5-108,1) and anti-SS-B antibodies (OR=11,8; 95%CI:1,5-94,8). Association with anti-cardiolipin and anti-prothrombin antibodies of IgG class was on the border of statistical significance (OR=2,3; 95%CI:0,9-5,7 and OR=8,4; 95%CI:1,0-71,1 respectively).
Conclusions 1. IL-23 may be involved in lupus nephritis pathogenesis. 2. IL-23 trough its significant association with obesity and antiphospholipid antibodies may promote hypercoagulable state contributing to atherothrombosis development in SLE patients.
Mok MY, Wu HJ, Lo Y, Lau CS. The relation of interleukin 17 (IL-17) and IL-23 to Th1/Th2 cytokines and disease activity in systemic lupus erythematosus. J Rheumatol; 2010; 37(10): 2046-52.
Manoharan A, Madaio MP. Biomarkers in lupus nephritis. Rheum Dis Clin North Am; 2010; 36(1): 131-43.
Disclosure of Interest None Declared