Sulfate metabolism is abnormal in patients with rheumatoid arthritis. Confirmation by in vivo biochemical findings

Abstract

Objective: To independently confirm previous probe drug findings that patients with rheumatoid arthritis (RA) have defective oxidation of cysteine derivatives.

Methods: Measurement of cysteine dioxygenase substrate (cysteine) and product (sulfate) under controlled conditions, with elemental assessment by proton induced x-ray emission (PIXE).

Results: 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.

Conclusions: These cysteine/sulfate findings confirm the validity of the previous probe drug abnormalities and the importance of defective cysteine dioxygenase activity in RA.