DNA AND NEUTROPHIL EXTRACELLULAR TRAPS RELEASE, NOVEL POTENTIAL BIOMARKERS AND THERAPEUTIC TARGETS OF JOINT DAMAGE IN HEMOPHILIA

CAVIGLIA, HORACIO; ONETO, P; LANDRO, ME; DAFFUNCHIO, C; AL DOUGLAS PRICE; SCHATTNER, M; ETULAIN, J

Congreso; 13th Annual Congress of the European Association for Haemophilia and Allied Disorders; 2020

European Association for Haemophilia and Allied Disorders

Introduction: 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 andmonocytes-induced inflammation are known players in this process. The role of neutrophils, major immune blood cellsinfiltrated in synovium after bleeding is unknown. Neutrophils release extracellular DNA traps (NETs), microbicidesstructures containing DNA fibers with bound granular enzymes as elastase. During chronic inflammation, a cytotoxiceffect of NETs has been associated with tissue damage in lung, kidney, skin and joints. Our aim is to elucidate the role ofneutrophils 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 23 patients (28±11 years old, 22Haemophilia type A, 1 type B). Chronic synovitis was present in 1 ankle and 22 knee joints that were evaluated forHaemophilia 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 withclinical parameters were calculated.Results: DNA (0.35±0.07μg/ml) and DNA-Elastase (0.27±0.03Abs) were detected in SF of CHS patients and they werepositively correlated with HJHS (r>0.5, p