Article Text

PDF
08.35 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
  1. Markos D Patsouras,
  2. Athanassios G Tzioufas,
  3. Panayiotis G Vlachoyiannopoulos
  1. Pathophysiology Department, Medical School, National and Kapodistrian University of Athens

Abstract

Background Antiphospholipid syndrome (APS) is an acquired thombophillia characterised by recurrent thromboembolism and

pregnancy morbidity. Thrombospondin (TSP-1) is a r glycoprotein secreted by platelets upon activation with proinflammatory,

antiangiogenic and proapoptotic properties. TSP-1 activates TGF-b1 and has been shown to be involved in TH-17 response. We aimed to investigate Thrombospondin-1 in APS.

Materials and methods Plasma, serum, and total IgG were isolated from 90 patients with APS, 46 healthy controls (HC) and 26 SLE patients. 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 TSP-1, IL-1β, IL-17A and free active TGF-β1 levels were determined using an ELISA.

Results APS patients had higher plasma levels of TSP-1 than HCs and SLE patients (APS: mean 390 ng/ml vs HC: 144.3 vs SLE: 153.0)

Patient plasma free active TGF-β1 levels were higher and strongly correlated with TSP-1 (r=0,827). Among the APS patients those with TSP-1 levels>600 ng/ml had IL-1b and IL-17A in their plasma.

APS HUVECs and HC HUVECs cultured with APS plasma expressed higher levels of TSP-1 copmared to their controls. (APS=139.4 ng/ml vs HC=22.8 ng/ml p=0,0009). Monocytes stimulated with APS total IgG produced higher levels of IL-1b and TSP-1 compared to their controls (700pg/ml vs 50pg/ml and 500 ng/ml vs 200 ng/ml respectively). APS stimulated supernatants induced IL-17A expression from T-cells (250pg/ml) whereas the HC had no effect.

Regarding the clinical aspects of APS, there was significant difference between the patients with pregnancy morbidity alone (130.1 ng/ml) and those with miscarriages and thrombosis (403.2 ng\ml).

Conclusions Preliminary results suggest that APS patients have higher TSP-1 plasma levels which correlate with free active TGF-β1. Monocytes and HUVECs treated with APS plasma and APS IgG produce higher levels of TSP-1 and IL-1b and these supernatants induce the IL-17A expression from T-cells.

All these suggest a possible involvement of TSP-1 in thrombus formation, inflammation and inhibition of angiogenesis that needs further study.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.