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Abstract
Background Thrombospondin-1 (TSP-1) is the most abundant protein inside platelet alpha-granules, being secreted upon their activation. The role of TSP-1 in thrombosis and hemostasis remains dubious, with conflicting data showcasing both protective and harmful mechanisms. As young patients with systemic lupus erythematosus (SLE) present a markedly heightened risk of MI, we aimed to assess plasma (p) levels of TSP-1 in order to discern their relevance as a marker for atherothrombosis. We further evaluated the correlation with venous thrombosis (VT), and specifically with pulmonary embolism (PE).
Methods TSP-1 levels were measured in plasma samples (SLE = 308, population controls (PC) = 308) from the Karolinska Biobank by a commercial ELISA kit (R&D Cat# DY3074), according to the manufacturer’s instructions. The 95th percentile of PC was used as a cut-off for high levels. Mann-Whitney U-test and Fisher’s exact test were used, with a significance level of p<0.05.
Results Levels of pTSP-1 were higher in SLE samples (mean of 12.3 ug/mL) as opposed to PC (mean of 10.1 ug/mL). When adopting the 95th percentile of healthy controls (19.23 ug/mL), a clear differentiation was evidenced (p<0.001), with 19% of SLE samples above the upper percentile. Absolute values of pTSP-1 were significantly higher in SLE patients with a history of MI (p=0.017) or PE (p=0.028), as compared to patients without those manifestations. Further, high levels of pTSP-1 were associated with past history of VT (p=0.038) in SLE. Our results are in contrast to previous works, which showed either reduction or no difference between levels in SLE versus in HC.
Conclusions In a large cohort of well-characterized SLE patients, pTSP-1 levels were found to be elevated, and associated with a history of MI or PE. The strength of our work relies on our robust sample size, well-characterized patient cohort, as well as inclusion of population cohort (instead of healthy controls). Future work aims to determine whether levels of pTSP-1 can predict development of thrombotic event in SLE.
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