To independently confirm previous probe drug findings that patients with rheumatoid arthritis (RA) have defective oxidation of cysteine derivatives.
Measurement of cysteine dioxygenase substrate (cysteine) and product (sulfate) under controlled conditions, with elemental assessment by proton induced x-ray emission (PIXE).
Plasma inorganic sulfate was significantly depressed in patients with rheumatoid arthritis (RA) compared to both controls and non-RA disease, 85 +/- 36 nm/ml vs 267 +/- 146 and 604 +/- 412 (mean +/- SD. RA patients vs non-RA disease p < 0.001). Fasting cysteine levels were significantly raised compared to controls (59 +/- 20 nm/ml vs 17 +/- 81 nm/ml p < 0.001). Synovial fluid (SF) sulfate was also significantly reduced in patients with RA compared to non-RA controls (202 +/- 117 nm vs 1041 +/- 700 p < 0.001). PIXE data confirmed the low sulfate levels in serum and SF while showing no reduction in the levels of other elements analyzed.
These cysteine/sulfate findings confirm the validity of the previous probe drug abnormalities and the importance of defective cysteine dioxygenase activity in RA.