MARKERS OF INFLAMMATION IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME AND CARDIOVASCULAR PATHOLOGY

Objective: to estimate the levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-α), and soluble TNF-α receptor type 1 (sTNF-R1) in patients with antiphospholipid syndrome (APS) and their association with cardiovascular pathology. Subjects and methods. Ninety-six patients, including 52 with primary APS and 44 with systemic lupus erythematosus and APS, were examined. A control group comprised 29 individuals without the signs of autoimmune disease. The levels of hsCRP, IL-6, TNF-α, sTNF-R1, antiphospholipid antibodies, and plasma lipids were studied; ultrasonography measuring the carotid intima-media complex (IMC), electrocardiography (ECG), echocardiography, and Holter ECG monitoring were made. Results. The concentrations of hsCRP, IL-6, TNF-α, and sTNF-R1 were significantly higher in the patient groups than in the controls (p < 0.05). Elevated sTNF-R1 concentrations were more common in angina pectoris than in its absence (OR = 2.13; 95% CI [1.51; 2.99]; p < 0.001). In patients with damage to the valvular apparatus, IL-6, TNF-α, and sTNF-R1 concentrations were significantly higher than those in patients without the defects (p = 0.02, 0.02, and 0.01, respectively). The levels of TNF-α and sTNF-R1 were significantly higher in hypertensive patients than those in non-hypertensives (p = 0.002 and p < 0.001; respectively). The blood concentration of TNF-α was significantly higher in patients having the risk factors and subclinical signs of atherosclerosis that that in those without the signs and risk factors of atherosclerosis (p < 0.05). Analysis showed a direct correlation between the levels of TNF-α, hsCRP, IL-6, and sTNF-R1 and an inverse correlation of those of IL-6 and TNF-α with the duration of posttrombosis (p < 0.05). A correlation was found between the concentrations of TNF-α and sTNF-R1, and IMC of the great arteries, as well as the cumulative coronary risk (p < 0.05). Conclusion. In patients with APS, the levels of all the test markers were significantly higher than those in the controls. An association was revealed between the values of TNF-α and sTNF-R1 and the risk factors and subclinical signs of atherosclerosis

Cytokines and neopterin in antiphospholipid syndrome

Objective. To study clinical significance of proinflammatory cytokines (tumor necrosis factor α – TNFα, interleukine 6 – IL6, IL18), soluble receptors of TNFα (sTNF-R), anti- inflammatory cytokines (IL10) and integral marker of cytokine-dependent cell immune response activation neopterin in antiphospholipid syndrome (APS).Material and methods. Serum concentration of cytokines and neopterin was evaluated by immunoenzyme assay with commercial kits “BioSource International, Inc.” (USA), “Bender MedSystems” (Austria) and “IBL” (Germany) in 39 pts with primary APS (PAPS), 53 pts with secondary APS (SAPS) associated with systemic lupus erythematosus (SLE), 164 pts with SLE and 54 healthy donors.Results. Level of Th1 cytokines (TNFα, IL18), sTNF-R and neopterin in PAPS, SAPS and SLE as well as Th2 cytokines (IL6, IL10) in SAPS and SLE were significantly higher than in donors (p&lt;0,05). TNFα elevation in PAPS was associated with damage of cardiac valves (p&lt;0,05) and CNS (p&lt;0,01), IL18 elevation – with chronic leg ulcers (p&lt;0,001). Most prominent sTNFα-R elevation in SAPS was revealed in pts with thrombocytopenia (p&lt;0,05). Neopterin hyperproduction in APS was associated with cardiac valve damage16 (p&lt;0,001). IL10 level elevation in APS correlated with decreased thrombosis history (r=- 0,4; p&lt;0,02), in SLE with APS – with decrease of damage score SLICC (r=-0,7; p&lt;0,001) what proves protective significance of IL10 in relation to thrombosis development and disease progression. Increased concentration of IL 18 was associated with atherogenic disturbances presented as hypertrigliceridemia (r=0,6; p&lt;0,01) and decrease of HDLP cholesterol (r—0,4; p&lt;0,01). Positive correlation between TNFα, IL6 and neopterin level, IgM anticardiolipine antibodies and IgG/IgM antiprothrombin antibodies (p&lt;0,05) was revealed. Cytokine, sTNFα-R and neopterin level elevation in SLE with APS was associated with increase of SLEDAI and ECLAM activity indices (p&lt;0,05). Conclusion. Cytokine and neopterin hyperproduction reflecting cell immunity activation and inflammation is an important factor of APS pathogenesis