The role of thrombospondin-1 in the pathogenesis of antiphospholipid syndrome.
J Autoimmun
; 115: 102527, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-32709480
ABSTRACT
OBJECTIVE:
Antiphospholipid syndrome (APS) is an acquired thrombophilia characterized by recurrent thrombosis and/or pregnancy morbidity, in the presence of antibodies to ß2 glycoprotein-I (ß2GPI), prothrombin or Lupus anticoagulant (LA). Anti-ß2GPI antibodies recognize complexes of ß2GPI dimers with CXCL4 chemokine and activate platelets. Thrombospondin 1 (TSP-1) is secreted by platelets and exhibits prothrombotic and proinflammatory properties. Therefore, we investigated its implication in APS.METHODS:
Plasma from APS patients (n = 100), Systemic Lupus Erythematosus (SLE) (n = 27) and healthy donors (HD) (n = 50) was analyzed for TSP-1, IL-1ß, IL-17A and free active TGF-ß1 by ELISA. Human Umbilical Vein Endothelial Cells (HUVECs) and HD monocytes were treated with total HD-IgG or anti-ß2GPI, ß2GPI and CXCL4 and CD4+ T-cells were stimulated by monocyte supernatants. TSP-1, IL-1ß, IL-17A TGF-ß1 levels were quantified by ELISA and Real-Time PCR.RESULTS:
Higher plasma levels of TSP-1 and TGF-ß1, which positively correlated each other, were observed in APS but not HDs or SLE patients. Patients with arterial thrombotic events or those undergoing a clinical event had the highest TSP-1 levels. These patients also had detectable IL-1ß, IL-17A in their plasma. HD-derived monocytes and HUVECs stimulated with anti-ß2GPI-IgG-ß2GPI-CXCL4 secreted the highest TSP-1 and IL-1ß levels. Supernatants from anti-ß2GPI-ß2GPI-CXCL4 treated monocytes induced IL-17A expression from CD4+ T-cells. Transcript levels followed a similar pattern.CONCLUSIONS:
TSP-1 is probably implicated in the pathogenesis of APS. In vitro cell treatments along with high TSP-1 levels in plasma of APS patients suggest that high TSP-1 levels could mark a prothrombotic state and an underlying inflammatory process.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Complicações Hematológicas na Gravidez
/
Trombose
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Síndrome Antifosfolipídica
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Trombospondina 1
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Lúpus Eritematoso Sistêmico
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Female
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Humans
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Male
/
Pregnancy
Idioma:
En
Revista:
J Autoimmun
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Grécia