Avaliação do perfil imunológico de pacientes com Hemofilia recém-diagnosticada

Abstract

Congenital hemophilia is a hemorrhagic disease resulted from deficiency of factor VIII (FVIII) in hemophilia A or IX (FIX) in individuals with hemophilia B. Hemophilia requires frequent infusions of FVIII or FIX concentrates for prophylaxis and/or treatment of hemorrhage. However, during treatment, approximately 30% and 5% of patients with hemophilia A and B, respectively, develop antibodies (inhibitors) which inhibit the coagulant activity of the infused factor promoting ineffective factor replacement. The pathophysiology related to the development of inhibitors is poorly understood. Previous studies have evaluated the immune profile of patients with hemophilia, but no study followed this profile at different stages of the disease. This project aims to evaluate the immunological profile of previously untreated patients before the start of factor replacement. For this, 32 patients were included in the hemophilia centers of Minas Gerais, Espirito Santo, Paraná and Rio de Janeiro, of which 28 (87.5%) with hemophilia A and 4 patients (12.5%) with hemophilia B. Upon inclusion, 22 (68.8%) patients received no factor VIII infusion and 10 (31.2%) had at most 4 days of exposure to factor VIII. The leukocyte phenotypic profile of 19 (59.4%) patients was assessed by using flow cytometry immunophenotyping. Furthermore, we also measured cytokines, chemokines and microparticles (MPs) in 28 (87.5%) patients with hemophilia A (PHA) and 47 controls, also by flow cytometry. We observed that the phenotypic profile of leukocytes in patients with hemophilia A is heterogeneous. Increased levels of MPs of platelets, leukocytes, T lymphocytes, neutrophils, monocytes and erythrocytes were found in previously untreated patients (0DE) when compared to controls (p <0.05). We also observed higher levels of IL-4, IL-6, IL-8 and IL-10 and lower levels of the MIG patients compared to controls (p <0.05). Patients with more than one exposure day to factor VIII (>1DE) showed elevated levels of IL-4, IL-6, IL-8, IL-10, TNF, IFN- and IL-2 compared to controls, including a reduction in the levels of MIG. In conclusion, we found that the immune profile modulated by cytokines and chemokines differ between previously untreated patients with hemophilia A, patients who had less than four exposure days to factor VIII and control group. This suggests that an immune response develops as a result from the attempt to control hemostasis in patients with hemophilia.