SULFATE METABOLISM IS ABNORMAL IN PATIENTS WITH RHEUMATOID-ARTHRITIS - CONFIRMATION BY IN-VIVO BIOCHEMICAL FINDINGS

Objective. To independently confirm previous probe drug findings that patients with rheumatoid arthritis (RA) have defective oxidation of cy steine derivatives. Methods. Measurement of cysteine dioxygenase subst rate (cysteine) and product (sulfate) under controlled conditions, wit h elemental assessment by proton induced x-ray emission (PIXE). Result s. Plasma inorganic sulfate was significantly depressed in patients wi th rheumatoid arthritis (RA) compared to both controls and non-RA dise ase, 85 +/- 36 nm/ml vs 267 +/- 146 and 604 +/- 412 (mean +/- SD. RA p atients vs non-RA disease p < 0.001). Fasting cysteine levels were sig nificantly raised compared to controls (59 +/- 20 nm/ml vs 17 +/- 81 n m/ml p < 0.001). Synovial fluid (SF) sulfate was also significantly re duced 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 ele ments analyzed. Conclusions. These cysteine/sulfate findings confirm t he validity of the previous probe drug abnormalities and the importanc e of defective cysteine dioxygenase activity in RA.