In juvenile rheumatoid arthritis (JRA), it is likely that the release of proteolytic enzymes from activated synovial fluid neutrophils overwhelms the major protease inhibitor, α2-macroglobulin (α2-MG), and leads to cartilage destruction. Due to the unique nature of the α2-MG-protease complex, proteolytic function is maintained until the complex is cleared. In this study, we sought to determine the concentration of α2-MG-protease complexes in synovial fluid of patients with JRA, the proteolytic activity found in their synovial fluid, and whether the α2-MG complexes are associated with increased proteolytic activity. The JRA patients’ synovial fluids had complex levels of 217.0 ± 192.2 nmol/L—significantly elevated compared with plasma values (p < 0.001) and with control synovial fluid (p < 0.05). Elastase activity (almost entirely neutrophil elastase) was detectable in all JRA synovial fluid samples (mean 2.9 ± 2.6 mg/L) and significantly correlated with α2-MG-complex values (r = 0.67, p < 0.01). Synovial fluid tryptic activity was detectable in all JRA patients but did not significantly correlate with α2-MG complexes (r = 0.53, p > 0.05). Seventy-four percent of total elastase activity and 41% of total tryptic activity were contained in the α2-MG-complex fractions. We suggest that the increased concentration of synovial fluid α2-MG complexes with retained elastase activity contributes to continued proteolysis and joint destruction and may affect the subsequent disease course through its role as a modulator of IL-6.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health