Intraarticular alpha 2-macroglobulin complexes and proteolytic activity in children with juvenile rheumatoid arthritis

Abstract

In juvenile rheumatoid arthritis (JRA), it is likely that the release of proteolytic enzymes from activated synovial fluid neutrophils overwhelms the major protease inhibitor, alpha 2-macroglobulin (alpha 2-MG), and leads to cartilage destruction. Due to the unique nature of the alpha 2-MG-protease complex, proteolytic function is maintained until the complex is cleared. In this study, we sought to determine the concentration of alpha 2-MG-protease complexes in synovial fluid of patients with JRA, the proteolytic activity found in their synovial fluid, and whether the alpha 2-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 detected in all JRA synovial fluid samples (mean 2.9 +/- 2.6 mg/L) and significantly correlated with alpha 2-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 alpha 2-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 alpha 2-MG-complex fractions. We suggest that the increased concentration of synovial fluid alpha 2-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.