Lupus & antiphospholipid syndrome
TWEAK /Fn14 Signaling Drives Oxidative Cardiac Injury in Systemic Lupus Erythematosus: Evidence From Patient Biomarker Studies, Lupus Mouse Models, and Cardiomyocyte Assays
Authors' conclusion
TWEAK/Fn14 signaling drives oxidative stress-mediated cardiomyocyte injury in SLE and represents a promising biomarker and therapeutic target for lupus-associated cardiac damage.
Study context
- Population
- Patients with systemic lupus erythematosus (SLE) and matched controls; pristane-induced lupus mice; cardiomyocytes from MRL/lpr mice
- Participants
- 242 vs 66
- Comparison
- SLE vs age- and sex-matched controls; Fn14-deficient vs wild-type lupus mice; TWEAK exposure in lupus-prone cardiomyocytes
- SLEn = 242
- Controlsn = 66reference
Methodological detailspatient biomarker study with age- and sex-matched controls, pristane-induced lupus mouse models (wild-type and Fn14-deficient), primary cardiomyocytes from lupus-prone MRL/lpr mice
- Patient biomarker study with age- and sex-matched controls
- Pristane-induced lupus mouse models (wild-type and Fn14-deficient)
- Primary cardiomyocytes from lupus-prone MRL/lpr mice
Main finding
As reported in the abstract
- Serum TWEAK significantly elevated in SLE, highest in those with cardiac abnormalities, vs healthy controls
- TWEAK correlated positively with malondialdehyde, 8-hydroxy-2'-deoxyguanosine, disease activity and inflammatory cytokines, inversely with superoxide dismutase
- Elevated baseline TWEAK predicted new cardiac abnormalities during follow-up and declined with clinical improvement
- In lupus mice, Fn14 deficiency reduced cardiac ROS, restored Nrf2/HO-1 signaling, attenuated histopathological injury and preserved cardiac function
- In vitro, TWEAK induced mitochondrial superoxide, suppressed Nrf2 signaling and promoted apoptosis in lupus-prone cardiomyocytes
Original publication
TWEAK /Fn14 Signaling Drives Oxidative Cardiac Injury in Systemic Lupus Erythematosus: Evidence From Patient Biomarker Studies, Lupus Mouse Models, and Cardiomyocyte Assays. Arthritis Rheumatol. Published 21 April 2026. doi:10.
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