Marcadores de ativação da doença e estado de hipercoagulabilidade no lúpus eritematoso sistêmico

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune and inflammatory disease characterized by the production of various autoantibodies and tissue deposits of circulating antigen-antibody complexes. The discovery and validation of methods for the determination of cell bound complement activation products (CB-CAPs), such as C4d bound to reticulocytes (R-C4d) and to platelets (P-C4d), as potential biomarkers of the activity state and the thrombotic potential of SLE, respectively, may be important tools for a better understanding of the pathophysiology and clinical management of SLE patients. Another important factor in the pathogenesis of SLE are the events resulting from hemostatic system abnormalities that need to be better understood. Thus, the main objective of this study was to evaluate whether the levels of CB-CAPs in SLE patients can be predictors of disease activity (R-C4d) and thrombotic predisposition (P-C4d). In addition to the CB-CAPs levels, the thrombotic potential was investigated by determining the plasma levels of important components of the hemostatic system such as D-dimer (DDi), thrombomodulin (TM), protein S (PS) and C4b binding protein (C4BP), seeking a possible association between these parameters and the others also investigated. To achieve this goal, a total of 60 patients with SLE, under treatment, selected at the Hospital Santa Casa Rheumatology Service in Belo Horizonte was included, with 30 LES patients classified as having low-disease activity (SLEDAI-2K 4) and 30 patients with moderate/high activity (SLEDAI-2K> 4), while 30 women without SLE (controls), matched by age and socioeconomic status were simultaneously selected. Blood samples collected from the study participants were used to determine the levels of CB-CAPs by means of flow cytometry and to obtain plasma for carrying out the other tests included in this study. Compared to both controls and SLE patients with low activity disease, increased levels of R-C4d, P-C4d, TM and DDi were observed in patients with SLE with moderate/high activity disease, whose levels correlated with the increase in the SLEDAI-2K index. PS and C4BP levels were similar among all three groups. Data analysis showed that high levels of R-C4d and P-C4d correlated with the SLEDAI-2K index and, therefore, with clinical worsening in SLE patients. Moreover, the combination of R-C4d and P-C4d allowed the establishment of a cutoff proposal as indicative of disease activity. Finally, it was possible to confirm the relationship between disease activity and hypercoagulability, probably associated with endothelial damage and inflammation.