Diminished expression of the ubiquitin-proteasome system in early treatment-naïve patients with rheumatoid arthritis and concomitant type 2 diabetes may be linked to IL-1 pathway hyper-activity; results from Pathobiology of Early Arthritis Cohort (PEAC) cohort
Authors' conclusion
A different IL-1 pathway gene expression was observed in the synovial tissues of early treatment-naïve RA/T2D patients, linked to decreased expression of the ubiquitin-proteasome system.
Study context
- Population
- Early (< 1 year) treatment-naïve rheumatoid arthritis (RA) patients enrolled in the Pathobiology of Early Arthritis Cohort (PEAC); FLSs from RA patients for in vitro experimentsFLSs from 5 RA patients · RA patients 5
- Participants
- 16 vs 16
- Comparison
- Early treatment-naïve RA with T2D vs age- and sex-matched RA without T2D
- RA/T2Dn = 16
- RA without T2Dn = 16reference
- Outcome
- Synovial expression of IL-1 pathway genes in relationship to the ubiquitin-proteasome system
Methodological detailsage- and sex-matched, synovial tissue gene expression, immunohistochemistry/immunofluorescence, in vitro FLS experiments
- Age- and sex-matched
- Synovial tissue gene expression
- Immunohistochemistry/immunofluorescence
- In vitro FLS experiments
Main finding
As reported in the abstract
Synovial gene expression, RA/T2D vs RA without T2D
- Ubiquitin genes (UBB, UBC, and UBA52) significantly lower in RA/T2D
- Proteasome subunit genes (PSMA2, PSMA6, PSMA7, PSMB1, PSMB3, PSMB4, PSMB6, PSMB8, PSMB9, PSMB10, PSMC1, PSMD9, PSME1, and PSME2) significantly lower in RA/T2D
- Fibroblast-function genes (FGF7, FGF10, FRS2, FGFR3, and SOS1) upregulated in RA/T2D
- IL-1 pathway hyper-activity genes (APP, IRAK2, and OSMR) upregulated in RA/T2D
- Significant reduction of the percentage of ubiquitin-positive cells in synovial tissues of RA/T2D (immunohistochemistry)
Further findings
Ubiquitin-positive cells by synovial pathotype
- Increased in lympho-myeloid pathotype vs diffuse myeloid or pauci-immune-fibroid
Ubiquitinated proteins in RA-FLSs treated with insulin (in vitro)
- Reduced with high concentration of insulin (500 nM)
Original publication
Diminished expression of the ubiquitin-proteasome system in early treatment-naïve patients with rheumatoid arthritis and concomitant type 2 diabetes may be linked to IL-1 pathway hyper-activity; results from PEAC cohort. Arthritis Res Ther. Published 28 September 2024. doi:10.
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