Gene expression regulated by abatacept associated with methotrexate and correlation with disease activity in rheumatoid arthritis.
Céline DerambureGaëlle Dzangué-TchoupouMaria Antonietta D'AgostinoThierry LequerréOlivier VittecoqPublished in: PloS one (2020)
In methotrexate/Abatacept responders, 672 genes were significantly (q<0.05) dysregulated at 6 months compared to baseline. Correlation analysis highlighted 19 genes whose dysregulations were significantly associated with disease activity variation (p<0.05) and whose functions were associated with proliferation, apoptosis of cells and mitochondrial metabolism, suggesting a restoration of oxidative signaling. The other 653 gene expression changes were relative to direct or indirect effects of methotrexate/Abatacept treatment and were significantly (p<0.005) involved in pathways relative to mRNA processing, proteasome, angiogenesis, apoptosis and TCR signaling. This study highlights new mechanisms of action of methotrexate/Abatacept and may provide new therapeutic targets to prevent autoimmunity in rheumatoid arthritis.
Keyphrases
- rheumatoid arthritis
- disease activity
- gene expression
- rheumatoid arthritis patients
- cell cycle arrest
- high dose
- ankylosing spondylitis
- oxidative stress
- cell death
- endoplasmic reticulum stress
- induced apoptosis
- dna methylation
- juvenile idiopathic arthritis
- genome wide
- systemic lupus erythematosus
- interstitial lung disease
- endothelial cells
- pi k akt
- signaling pathway
- low dose
- regulatory t cells
- genome wide identification
- transcription factor
- immune response
- vascular endothelial growth factor
- dendritic cells
- binding protein
- combination therapy