RESUMEN
Background This study was performed to assess adhesion molecules in systemic lupus erythematosus (SLE). Methods This case-control study examined 126 SLE patients and 48 healthy individuals. Blood levels of six adhesion molecules, cortisol, nuclear autoantibody (ANA) and anti-double stranded DNA (anti-dsDNA) titers were measured, while disease activity was assessed using the SLE Disease Activity Index (SLEDAI) score. Results Platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, P-selectin, and plasminogen activator inhibitor type-1 (PAI-1) were significantly higher in SLE patients than in controls. Binary logistic regression analysis showed that PECAM-1 and PAI-1 predicted SLE with a sensitivity of 86.5% and a specificity of 81.3%. ANA titers were significantly and positively associated with PECAM-1, VCAM-1, E-selectin, and PAI-1, whereas there were no associations between anti-dsDNA titers and adhesion molecules. Cortisol was negatively associated with PCAM-1 and ICAM-1. There were significant associations between metabolic syndrome (MetS) and E-selectin and PAI-1. 14.8% of the variance in the SLEDAI score was explained by the regression on PECAM-1 and MetS. Conclusions Our data show that adhesion molecules, especially PECAM-1, are significantly associated with SLE and disease activity, suggesting that they play a role in SLE pathophysiology. While MetS, ANA titers and cortisol levels modulate adhesion molecule levels, these associations do not explain the increased levels of adhesion molecules in SLE. Increased levels of adhesion molecules are new drug targets in SLE.
Asunto(s)
Anticuerpos Antinucleares/sangre , Autoinmunidad , Moléculas de Adhesión Celular/sangre , Hidrocortisona/sangre , Lupus Eritematoso Sistémico/sangre , Síndrome Metabólico/complicaciones , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Brasil , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Índice de Severidad de la EnfermedadRESUMEN
The aims of the present study were to evaluate biomarkers of oxidative and nitrosative stress in systemic lupus erythematosus (SLE) patients, in particular products of DNA/RNA oxidative damage and their correlation with disease activity. This study included 188 controls and 203 patients; 153 with inactive SLE (SLEDAI < 6) and 50 with active SLE (SLEDAI ≥ 6) without renal impairment. Oxidative stress was assessed by tert-butyl hydroperoxide-initiated by chemiluminescence, advanced oxidation protein products (AOPP), total radical-trapping antioxidant parameter (TRAP), nitric oxide metabolites (NOx), and DNA/RNA oxidation products. Patients with SLE showed increased oxidative stress, as demonstrated by the augmentation of lipid hydroperoxides ( p < 0.0001) and AOPP ( p < 0.001) and reduced total antioxidant capacity ( p < 0.0001), without differences between patients with active disease and in remission. NOx levels and DNA/RNA oxidation products were inversely and independently associated with disease activity ( p < 0.0001 and p = 0.021, respectively), regardless of BMI and prednisone use. The linear regression analysis showed that about 5% of the SLEDAI score can be explained by the levels of DNA/RNA oxidation products ( r2:0.051; p = 0.002) and about 9% of this score by the levels of NOx ( r2:0.091; p < 0.0001). This study provides evidence for an inverse association between serum NOx levels and DNA/RNA oxidation products and SLE disease activity, suggesting that oxidative/nitrosative stress markers may be useful in evaluating SLE disease activity and progression of the disease.