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Characterization of plasmacytoid dendritic cell activity and type 1 interferon signature in primary antiphospholipid syndrome with thrombosis

Grant number: 19/20891-3
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2020
Effective date (End): February 28, 2021
Field of knowledge:Health Sciences - Medicine
Principal researcher:Fernanda Loureiro de Andrade Orsi
Grantee:Ana Paula Rosa dos Santos
Home Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:16/14172-6 - Investigation of the pathophysiological aspects and novel therapeutic approaches for thromboembolic disorders, AP.TEM

Abstract

Antiphospholipid syndrome (APS) is a serious thrombotic disease characterized by production of autoantibodies against phospholipids, or phospholipid-binding proteins, present in the outer membranes of endothelial cells, monocytes and platelets. Thrombotic events in APS are believed to have a pathophysiological basis as immune reaction in these cell membranes, which causes activation of the cells and subsequently procoagulant stimulation. The mechanisms by which there is loss tolerance to membrane phospholipids and stimulation of autoantibody production are not established. Plasmacytoid dendritic cells (pDCs) are characterized by the ability to produce large amounts of interferon (IFN)-1, responsible for mediating the onset of the immune response. Animal model studies demonstrated activation of pDCs in Systemic Lupus Erythematosus (SLE). Clinical data show that 90% of children and more than 50% of adults with SLE have IFN-1 mediated pathological immune activity. It is possible that exacerbated activation of the innate immune system in APS, similar to what has already been described in SLE. However, the importance of these cells and IFN-1 expression in the pathogenesis of primary APS is not yet clear. In this way, the aim of this study is to characterize the pDCs immune response without patients with thrombosis related to APS. This will be a control case study where we will compare thrombotic primary APS patients, individuals with antiphospholipid antibodies without thrombosis or other complications of APS and healthy individuals pDCs and the presence of IFN-1 signature. We will use flow cytometry methods to quantify peripheral blood pDCs and IFN-± in the cytoplasm of these cells. We will also evaluate the relative expression of five IFN-1 inducing genes: Ly6E, OAS1, OASL, ISG15 and MX1. The quantification of TNF-alpha, IL-6, IL-8 cytokines will be performed by ELISA. The results will have the potential to identify whether activation of pDCs is associated with APS. Knowledge about the role of the innate immune system could help new treatments for APS be tested in the future. (AU)

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