Intraarticular α<inf>2</inf>-macroglobulin complexes and proteolytic activity in children with juvenile rheumatoid arthritis

Jeremiah J. Levine, David D. Sherry, Dudley K. Strickland, Norman Todd Ilowite

Research output: Contribution to journalArticle

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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, α<inf>2</inf>-macroglobulin (α<inf>2</inf>-MG), and leads to cartilage destruction. Due to the unique nature of the α<inf>2</inf>-MG-protease complex, proteolytic function is maintained until the complex is cleared. In this study, we sought to determine the concentration of α<inf>2</inf>-MG-protease complexes in synovial fluid of patients with JRA, the proteolytic activity found in their synovial fluid, and whether the α<inf>2</inf>-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 α<inf>2</inf>-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 α<inf>2</inf>-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 α<inf>2</inf>-MG-complex fractions. We suggest that the increased concentration of synovial fluid α<inf>2</inf>-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.

Original languageEnglish (US)
Pages (from-to)204-207
Number of pages4
JournalPediatric Research
Volume34
Issue number2
StatePublished - 1993

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Macroglobulins
Juvenile Arthritis
Synovial Fluid
Peptide Hydrolases
Pancreatic Elastase
Protease Inhibitors
Proteolysis
Cartilage
Interleukin-6
Neutrophils
Joints

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Intraarticular α<inf>2</inf>-macroglobulin complexes and proteolytic activity in children with juvenile rheumatoid arthritis. / Levine, Jeremiah J.; Sherry, David D.; Strickland, Dudley K.; Ilowite, Norman Todd.

In: Pediatric Research, Vol. 34, No. 2, 1993, p. 204-207.

Research output: Contribution to journalArticle

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