Background Protein S plays a role as a cofactor not only in coagulation pathway, but also in the removal of apoptotic remnants. Free protein S was investigated whether it could represent as a disease related marker in systemic lupus erythematosus (SLE), which has a defect in clearance of apoptotic debris1,2. In SLE, cardiovascular diseases including myocardial infarction and stroke develop more frequently and earlier than healthy population. It has become important to find underline mechanisms about the advanced atherosclerosis in SLE3.
Objectives We measured free protein S and carotid atherosclerosis using Doppler sonography among SLE patients, and analyzed their associations with clinical features including disease activity markers.
Methods Total of 110 female patients with SLE were recruited and serum free protein S level was evaluated by enzyme-linked immunosorbent assay. The carotid artery intima media thickness (cIMT) and plague were measured by Doppler ultrasound and the clinical characteristics were collected.
Results Mean level of free protein S was 67.4±19.7%, and 21 patients had low level of free protein S, defined as less than 50%. Hemoglobin and lymphocyte count were significantly lower (11.4±1.4 vs 12.5±1.4, p=0.002 and 1, 221±609 vs 1,720±1,097, p=0.047), and erythrocyte sedimentation rate (ESR) was significantly higher (30.1±20.6 vs 20.8 ± 17.8, p=0.033), complement 3 (C3) and complement4 (C4) were significantly lower (80.8±27.6 vs 103.4±25.8, p=0.001 and 15.6±10.4 vs 21.5±7.6, p=0.005) in SLE patients with low free proteins S level compared to those not. Carotid IMT levels were different (3.78±0.69 vs 4.13±0.87, p=0.051) while plaque index was not different between two groups. On univariate logistic analysis, hemoglobin (OR 0.6, p=0.003), lymphocyte (OR 1.0, p=0.03), ESR (OR 1.03, p=0.041), C3 (OR 0.96, p=0.001), and C4 (OR 0.91, p=0.007) were related with free protein S. With adjustments, hemoglobin (OR 0.57, p=0.023), C3 (OR 0.94, p=0.017) and cIMT (OR 0.51, p=0.046) were associated with low free protein S.
Conclusions Hemoglobin, complement 3 and cIMT were independently associated with low free protein S in SLE patients. Moreover, cIMT showed negative influence to low free protein S. From this clinical data, endothelial thickness might contribute free protein S rise in SLE patients.
Recarte-Pelz P et al. Vitamin K-dependent proteins GAS6 and protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity. Arthritis Res Ther. 2013;15:R41
Suh CH et al. TAM receptor ligands in lupus: Protein S but not Gas6 levels reflect disease activity in systemic lupus erythematosus. Arthritis Res Ther. 2010;12:R146.
Ruiz-Limon P et al. Atherosclerosis and cardiovascular disease in systemic lupus erythematosus: effects of in vivo statin treatment. Ann Rheum Dis. 2015;74:1450–8
Disclosure of Interest None declared