Background SLE patients have a marked increased risk of venous (VTE) and arterial (AT) thrombosis, which is not fully explained by traditional risk factors or the presence of anti-phospholipid antibodies. Thrombosis is a major cause of damage accrual, morbidity, and mortality in SLE. A better understanding of the pathogenesis and development of new biomarkers to identify patients at risk are needed. Recent studies link leptin and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) to subclinical atherosclerosis and galectin-3-binding protein (G3BP) to type I interferon activation and a pro-thrombotic environment.
Objectives To explore G3BP, interferon gamma-induced protein 10 (IP-10), soluble CD163 (sCD163), TWEAK, and leptin serum levels as predictors of venous and arterial thrombotic events, damage accrual, and all-cause mortality during long-term follow-up in a large cohort of Swedish SLE patients.
Methods Baseline clinical and paraclinical data including disease activity and damage scores (SLICC) were available from 167 SLE patients. VTE (deep vein thrombosis and/or pulmonary embolism) and AT (myocardial infarction and/or cerebrovascular incident) data were available with a median follow-up period of six years. Baseline serum G3BP, IP-10, sCD163, TWEAK, and leptin were quantified using ELISA. Univariate and multivariate analyses were conducted to asses associations between the serum biomarkers and the occurrence of VTE/AT, damage accrual, and death.
Results In the follow-up period 11 (7%) VTE and 12 (7%) AT events occurred. SLICC-scores increased in 79 (47%) patients, and 19 (11%) patients died. In the univariate Cox regression analysis G3BP levels were significantly associated with an increased risk of VTE (hazard ratio (HR) 1.10, 95% confidence interval (CI): 1.01–1.2, P=0.03). This persisted in the multivariate cox regression analyses when adjusting for age, gender, diabetes, antiphospholipid syndrome, and treatment with warfarin (HR 1.16, 95% CI: 1.04–1.31, P=0.01). None of the other serum biomarkers were associated with AT and VTE. No significant associations were observed between the biomarkers and changes in SLICC-scores or all-cause mortality.
Conclusions Our study identifies serum G3BP as a novel independent predictor of VTE in SLE. This may improve our understanding of VTE pathogenesis in SLE and aid future VTE risk stratification and prophylaxis. Further studies are needed to translate this into clinical practice.
Disclosure of Interest None declared
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