Counteracting tryptophan metabolism alterations as a new therapeutic strategy for rheumatoid arthritis
Authors' conclusion
Altogether, our preclinical and clinical data indicate that alterations in the Trp metabolism play an active role in the pathogenesis of RA and could be considered as a new therapeutic avenue.
Study context
- Population
- Previously untreated patients with rheumatoid arthritis (RA) (ESPOIR cohort), healthy subjects, established RA validation cohort; Collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) mice
- Participants
- 574 / 98 / 69
- Comparison
- Patients with RA vs healthy controls; recombinant aminoadipate aminotransferase in the CAIA model
- RAn = 574
- Healthyn = 98reference
- Established RAn = 69
- Outcome
- Serum Trp metabolites, RA vs healthy controls
Methodological detailstargeted quantitative tryptophan (Trp) metabolomics, validation cohort, experimental arthritis models (CIA, CAIA), proof-of-concept study
- Targeted quantitative Trp metabolomics
- Validation cohort
- Experimental arthritis models (CIA, CAIA)
- Proof-of-concept study
Main finding
As reported in the abstract
- Decreased levels of KYNA and XANA acids and indole derivatives in serum of patients with RA
- Increased level of QUIN in serum of patients with RA
- Changes correlated positively with disease severity and negatively with quality-of-life scores
- Similar kynurenine pathway profiles in CAIA and CIA models
- QUIN favours human fibroblast-like synoviocyte proliferation, inducing mitochondrial respiration and glycolysis
- Systemic recombinant aminoadipate aminotransferase was protective in the CAIA model
Original publication
Counteracting tryptophan metabolism alterations as a new therapeutic strategy for rheumatoid arthritis. Ann Rheum Dis. Published 15 February 2024. doi:10.
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