Intraarticular α₂-macroglobulin complexes and proteolytic activity in children with juvenile rheumatoid arthritis

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.