Type I Interferon Signature in Primary Antiphospholipid Syndrome

• Grant number: 14/17965-1
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2016 - April 30, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Danieli Castro Oliveira de Andrade
• Grantee: Danieli Castro Oliveira de Andrade
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Dirce Maria Carraro ; Michelle Remião Ugolini Lopes

Abstract

Background: Type I Interferon(IFN) is a key element in the pathogenesis of systemic lupus erythematosus (SLE). About half of lupus patients have predominant expression of interferon-induced genes in peripheral blood mononuclear cells (PBMC), known as interferon singnature. Interferon has a central role in autoimmunity acting as a bridge between innate and adaptive immune response. It is also an important cytokine with anti-angiogenic properties, down regulating the differentiation of endothelial progenitor cells and the expression of some proteins such as vascular endothelial growth factor (VEGF). Recent research have pointed out INF as an inducer of atherosclerotic plaque. The antiphospholipid syndrome (APS) is an autoimmune vasculopathy mediated by autoantibodies with thrombosis as the main clinical manifestation. The presence of antiphospholipid antibodies while extremely important does not seem sufficient to explain fully the pathophysiology of the disease. Recent studies have pointed toll like receptors and INF as possible adjuncts, working as a second trigger for the onset of thrombosis. As described in SLE, we hypothesized that IFN plays a major role in the pathogenesis of this disease. Objectives: To investigate whether APS patients present interferon signature in PBMCs. Methods: 50 female patients diagnosed with primary APS will be studied according to Sydney´s criteria, age greater than or equal or to 18 years, selected from the HCFMUSP Outpatient Rheumatology Clinic. They will be matched for age and sex with 50 positive controls (patients with a history of thrombosis resulting from non-immune-mediated thrombophilia) and 50 negative controls (healthy controls). PBMCs will be purified by Ficoll method. The gene expression of PBMCs will be analysed by TaqMan ®RNA Assay in TLDA plates. 41 INF induced genes will be searched. (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)

UGOLINI-LOPES, MICHELLE REMIAO; TORREZAN, GIOVANA TARDIN; ROSSI GANDARA, ANA PAULA; RIBEIRO OLIVIERI, ELOISA HELENA; NASCIMENTO, IANA SOUZA; OKAZAKI, ERICA; BONFA, ELOISA; CARRARO, DIRCE MARIA; OLIVEIRA DE ANDRADE, DANIELI CASTRO. Enhanced type I interferon gene signature in primary antiphospholipid syndrome: Association with earlier disease onset and preeclampsia. AUTOIMMUNITY REVIEWS, v. 18, n. 4, p. 393-398, APR 2019. (14/17965-1)