Downregulation of Tryptophan-related Metabolomic Profile in Rheumatoid Arthritis Synovial Fluid
Bibliographic record
Abstract
OBJECTIVE: Synovial fluid (SF) is one of the most important materials that reflect the pathophysiological process of arthritis. A metabolomic and lipidomic study of SF was performed with the aim of identifying tentative diagnostic markers or therapeutic candidates for rheumatoid arthritis (RA). METHODS: SF was aspirated from 10 patients with RA and 10 patients with osteoarthritis (OA). RA SF and OA SF were collected and analyzed by ultraperformance liquid chromatography quadruple time-of-flight mass spectrometry. Associations among clinical variables, laboratory results, and metabolic profiles were investigated. RESULTS: The metabolic pathways for carnitine, tryptophan, phenylalanine, arachidonic acid, and glycophospholipid were significantly upregulated in OA SF. The metabolic pathways for taurine, cholesterol ester, and the β-oxidation of pristine acid, linolenic acid, and sphingolipid were activated more in RA SF than in OA SF. In particular, the tryptophan pathway, which comprises kynurenine, indoleacetic acid, indole acetaldehyde, and N'-formylkynurenine, was downregulated. Interestingly, the levels of tryptophan metabolites kynurenine and N'-formylkynurenine, which are involved in immune tolerance, were significantly lower in RA SF compared with OA SF (p < 0.05), but the opposite pattern was observed for erythrocyte sedimentation rate (p < 0.01) and the levels of C-reactive protein (CRP; p < 0.01), rheumatoid factor (p < 0.01), and anticyclic citrullinated peptide antibody (p < 0.05). Kynurenine concentration correlated inversely with CRP concentration in RA SF but not in OA SF (r -0.65, p < 0.05). CONCLUSION: Advances in metabolomic techniques enabled us to delineate distinctive metabolic and lipidomic profiles in RA SF and OA SF. RA SF and OA SF showed distinct metabolic profiles.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".