Assuntos
Hemofilia A , Hemofilia B , Humanos , Hemofilia A/epidemiologia , Prevalência , Hemofilia B/epidemiologiaRESUMO
Up to 35% of patients with hemophilia A and 5% with hemophilia B develop neutralizing antibodies which can inhibit the therapeutic activity of factor replacement (inhibitors). Despite the clinical relevance of antifactor VIII and IX neutralizing antibodies, there is still a major gap on the knowledge of risk factors for their development. Furthermore, most of the studies on risk factors for inhibitor development come from Caucasian and Afro-American populations. The HEMFIL is a Brazilian prospective cohort study of previously untreated children with hemophilia, which primary aim is to identify new risk factors related to inhibitor development. This manuscript aims at describing the study design and its methodology. After the diagnosis, children are followed up to 75 exposure days or to inhibitor development. Standardized forms and blood samples are collected to describe clinical characteristics and to perform the measurement of immunological and genetic biomarkers at three time points; Inclusion time (T0), at inhibitor development or at 75 exposure days without inhibitors (T1) and after immune tolerance induction for patients in whom it is indicated and performed (T2). Currently, 120 children have been included, of whom, 95 have completed the follow-up. For severe/moderately severe hemophilia A, the cumulative incidence of inhibitors at 75 exposure days was 35% (95% confidence interval, 26-46%). The inclusion of additional patients and a longer follow-up will allow the analysis of risk factors for inhibitor development.
Assuntos
Anticorpos Neutralizantes/imunologia , Formação de Anticorpos , Fator VIII/imunologia , Hemofilia A/imunologia , Brasil/epidemiologia , Fator VIII/uso terapêutico , Feminino , Hemofilia A/epidemiologia , Hemofilia A/terapia , Hemofilia B/epidemiologia , Hemofilia B/imunologia , Hemofilia B/terapia , Humanos , Tolerância Imunológica , Lactente , Masculino , Estudos Prospectivos , Fatores de RiscoAssuntos
Alelos , Inibidores dos Fatores de Coagulação Sanguínea/imunologia , Hemofilia A/genética , Hemofilia A/imunologia , Isoanticorpos/imunologia , Lactase/genética , Polimorfismo de Nucleotídeo Único , Brasil/epidemiologia , Frequência do Gene , Genótipo , Hemofilia A/tratamento farmacológico , Hemofilia A/epidemiologia , Humanos , Índice de Gravidade de DoençaRESUMO
Previous cross-sectional studies showed that some patients with haemophilia A (HA) without inhibitor presented a pro-inflammatory profile during factor VIII (FVIII) replacement therapy. Furthermore, an anti-inflammatory/regulatory state was described in HA patients after inhibitor development. However, no study investigated the levels of these biomarkers before exposure to exogenous FVIII. This study investigated the immunological profile of previously untreated patients (PUPs) with HA in comparison with non-haemophiliac boys. A panel of chemokines and cytokines was evaluated in the plasma of 40 PUPs with HA and 47 healthy controls. The presence of microparticles was assessed in the plasma of 32 PUPs with HA and 47 healthy controls. PUPs with HA presented higher levels of CXCL8 (IL8), IL6, IL4, IL10, IL2, IL17A (IL17), and lower levels of CXCL10 (IP-10) and CCL2 (MCP-1) than the age-matched healthy controls (P < 0·05). We also observed higher levels of microparticles derived from endothelium, erythrocytes, platelets, leucocytes, neutrophils, and T lymphocytes in patients in comparison with controls (P < 0·05). Compared with controls, PUPs with HA presented a distinct immunological profile, characterized by a prominent pro-inflammatory status that appears to be regulated by IL4 and IL10.
