Hypoxia-induced upregulation of the glycolytic enzyme glucose-6-phosphate isomerase perpetuates rheumatoid arthritis.

Intra-articular hypoxia in the inflamed rheumatoid joint is associated with increased cell proliferation, enhanced metabolism and compromised vascular perfusion. Recent clinical studies using direct measurements of hypoxia in rheumatoid joints have delineated up to 20% of soft tissue pO(2) readings as below 10mm Hg. Increased markers for glycolysis exist in rheumatoid synovial fluid and upregulation of tissue glycolytic enzymes occurs in a rat model of synovitis. Recent reports show arthritis is provoked by linked T and B cell lymphocyte recognition of the glycolytic enzyme glucose-6-phosphate isomerase (GPI). This suggests an unusual physiological feature of rheumatoid joints leads to autoimmune destruction. In this report I suggest that hypoxia, within the rheumatoid joint, leads to upregulation of the glycolytic enzyme GPI which in turn perpetuates rheumatoid arthritis.