Background/Purpose: Antiphospholipid syndrome (APS) is an acquired thombophillia characterized by recurrent thromboembolism and pregnancy morbidity. Thrombospondin (TSP-1) is a matricellular glycoprotein secreted by platelets upon activation with proinflammatory, antiangiogenic and pro-apoptotic properties. TSP-1 activates TGF-β₁ and has been shown to be involved in TH-17 response. We aimed to investigate the role of Thrombospondin-1 in APS.

Methods: The study involved 90 patients with APS, 46 healthy controls (HC) and 26 SLE patients. Plasma, serum, and total IgG were isolated from all groups. Monocytes and CD4+ T-cells were isolated from 4 HC. Human Umbilical Vein Endothelial Cells were isolated from 2 APS patients and 5 HC and cultured with plasma or total IgG from HC or APS patients. Monocytes were stimulated with total IgG and these supernatants were used to stimulate CD4+ T-cells. Plasma and cell culture supernatant were analyzed for the presence of: TSP-1, IL-1b, IL-17A and free active TGF-b₁ levels using an ELISA.

Results: APS patients had higher plasma levels of TSP-1 than HCs and SLE patients (APS: mean 390ng/ml vs HC: 144.3 vs SLE: 153.0 p<0.0001) Patient plasma free active TGF-b1 levels were higher and strongly correlated with TSP-1 (r =0.827 and p<0.0001). Among the APS patients those with TSP-1 levels >600ng/ml had detectable IL-1b and IL-17A in their plasma. APS HUVECs cultured under standard conditions and HC HUVECs cultured with APS plasma expressed higher levels of TSP-1 than HC HUVECs cultured with HC plasma. (APS=139.4ng/ml vs HC=22.8ng/ml p=0.0009). Monocytes stimulated with APS total IgG produced higher levels of IL-1b and TSP-1 compared to the ones stimulated with HC IgG (700pg/ml vs 50pg/ml and 500ng/ml vs 200ng/ml respectively). APS stimulated supernatants induced the expression of IL-17A from healthy donor T-cells (250pg/ml) whereas the HC had no effect.  Patients with APS and pregnancy morbidity alone expressed lower TSP-1 levels (130.1ng/ml) than APS patients with miscarriages and thrombosis (403.2ng\ml).

Conclusion: Preliminary results suggest that APS patients have higher TSP-1 plasma levels which correlate with free active TGF-b1. Monocytes and HUVECs treated with APS plasma and APS IgG produce higher levels of TSP-1 and IL-1b and these supernatants induce the expression of IL-17A from naïve T-cells. All these suggest a possible involvement of TSP-1 in thrombus formation, inflammation and inhibition of angiogenesis that needs further study.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/thrombospondin-1-is-elevated-in-the-plasma-of-patients-with-antiphospholipid-syndrome-and-is-correlated-with-free-active-tgf-b1-levels-il-1b-and-il-17a/