Lymphocyte activation gene 3 is increased and affects cytokine production in rheumatoid arthritis
Authors' conclusion
sLAG-3 in the plasma and synovial fluid is increased in both early and chronic RA patients, particularly in the inflamed joint. High levels of sLAG-3 are associated with autoantibody seropositivity and radiographic progression in eRA, and LAG-3 plays a biologically active role in cRA by decreasing inflammatory cytokine production. This functional outcome is not affected by Gal-3 interference.
Study context
- Population
- Early and chronic rheumatoid arthritis (RA) patients and healthy controls
- Participants
- 99 / 32 / 38
- Comparison
- sLAG-3 in early RA vs healthy controls; synovial fluid vs plasma in chronic RA
- eRAn = 99
- Healthy controls (HC)n = 32reference
- cRAn = 38
Methodological detailsflow cytometry, surface plasmon resonance, cell cultures
- Flow cytometry
- Surface plasmon resonance
- Cell cultures
Main finding
As reported in the abstract
- Baseline plasma sLAG-3 increased in eRA vs HC and remained significantly elevated throughout 12 months of treatment
- High baseline sLAG-3 associated with IgM-RF, anti-CCP and radiographic progression
- In cRA, sLAG-3 significantly increased in synovial fluid (SF) vs plasma; LAG-3 primarily expressed by activated T cells in synovial fluid mononuclear cells (SFMCs) vs peripheral blood mononuclear cells (PBMCs)
- Recombinant human LAG-3 decreased cytokine secretion in RA cell cultures; antagonistic LAG-3 antibody increased it
- Dose-dependent binding between LAG-3 and Gal-3 by surface plasmon resonance (SPR); Gal-3 inhibition did not further change cytokine production
Original publication
Lymphocyte activation gene 3 is increased and affects cytokine production in rheumatoid arthritis. Arthritis Res Ther. Published 7 June 2023. doi:10.
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