Circulating cell-free DNA promotes inflammation in dermatomyositis patients with anti-NXP2 antibodies via the cGAS/STING pathway
Authors' conclusion
Increased ccf-DNA levels may be potential biomarkers for monitoring disease activity in anti-NXP2 antibody-positive DM. Activation of the cGAS/STING pathway is associated with PFA. Our findings identified a pathogenic effect of ccf-DNA on skeletal muscle via the cGAS/STING pathway.
Study context
- Population
- Patients with anti-NXP2 antibody-positive DM
Methodological detailsin vitro
- In vitro
Main finding
As reported in the abstract
- Increased Circulating cell-free DNA (ccf-DNA) levels positively correlated with MYOACT scores in anti-NXP2 antibody-positive DM
- Cytosolic DNA-sensing pathway upregulated; increased cytosolic dsDNA colocalized with cGAS in skeletal muscle
- cGAS/STING pathway activated in patients with PFA but not in patients without PFA (western blot)
- Increased IFN-I scores in patients with and without PFA
- Sera from patients with PFA increased p-STING expression in C2C12 cells; DNase I and STING inhibitor each inhibited it
Original publication
Circulating cell-free DNA promotes inflammation in dermatomyositis patients with anti-NXP2 antibodies via the cGAS/STING pathway. Rheumatology (Oxford). Published 7 August 2024. doi:10. 1093/ rheumatology/ keae425
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