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

• Grant number: 19/20891-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2020
• End date: February 28, 2021
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Fernanda Loureiro de Andrade Orsi
• Grantee: Ana Paula Rosa dos Santos
• Host 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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ROSA DOS SANTOS, ANA PAULA; VAZ, CAMILA DE OLIVEIRA; HOUNKPE, BIDOSSESSI WILFRIED; JACINTHO, BRUNA CARDOSO; OLIVEIRA, JOSE DIOGO; TRIPIQUIA VECHIATTO MESQUITA, GABRIELA LISIANE; DOS SANTOS, IRENE PEREIRA; ANNICHINO-BIZZACCHI, JOYCE; APPENZELLER, SIMONE; MAZETTO FONSECA, BRUNA DE MORAES; et al. Association between interferon-I producing plasmacytoid dendritic cells and thrombotic antiphospholipid syndrome. Lupus, v. N/A, p. 11-pg., 2022-05-25. (16/14172-6, 19/20891-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SANTOS, Ana Paula Rosa dos. Characterization of plasmocytoid dendritic cell activity and type 1 interferon signature in thrombotic antiphospholipid syndrome. 2022. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.