CONICET | Buscador de Institutos y Recursos Humanos

Background and aims: Hemarthroses cause major morbidity in hemophilia resulting in chronic hemophilic synovitis (CHS), osteochondral degeneration and arthropathy. Although the initial events causing joint damage remain uncertain, iron and monocytes-induced inflammation are known players in this process. The role of neutrophils, major immune blood cells infiltrated in synovium after bleeding is unknown. Neutrophils release extracellular DNA traps (NETs), microbicides structures containing DNA fibers with bound granular enzymes as elastase. During chronic inflammation, a cytotoxic effect of NETs has been associated with tissue damage in lung, kidney, skin and joints. Our aim is to elucidate the role of neutrophils in CHS by studying the formation of synovial NETs and its correlation with joint damage. Methods: Synovial fluids (SF) and peripheral blood-derived plasma were obtained from 16 patients (29±11 years old, 15 Haemophilia type A, 1 type B). Chronic synovitis was present in 1 ankle and 16 knee joints that were evaluated for Haemophilia Joint Health Score (HJHS). NETs in SF and plasma were indirectly determined by quantification of DNA (fluorometry) and directly by measuring DNA-Elastase complexes (ELISA). Pearson or Spearman correlations with clinical parameters were calculated. Results: DNA (0.39±0.09μg/ml) and DNA-Elastase (0.25±0.03Abs) were detected in SF of CHS patients and they were positively correlated with HJHS (r>0.5, p0.05) with the synovial levels of both parameters. Conclusions: Our data demonstrate that NETs are formed in synovium of CHS patients. The positive correlation of synovial DNA and DNA-Elastase levels with joint damage suggests that synovial NETs formation might be a potential therapeutic target for CHS. Moreover, the strong correlation of synovial and plasma levels of NETs suggests that circulating NETs represents a potential biomarker of CHS evolution.