EXPRESSION OF ANTI-INFLAMMATORY BIOMARKERS BY PERIPHERAL BLOOD REGULATORY T CELLS IN PREGNANT WOMEN WITH PRE-ECLAMPSIA

• Grant number: 23/17023-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): June 01, 2024
• Effective date (End): July 31, 2027
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Maria Terezinha Serrão Peraçoli
• Grantee: Patrícia Braga da Silva
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Preeclampsia is a pregnancy-specific syndrome, characterized by an adaptive immune response shifted towards an inflammatory profile and mediated by subpopulations of CD4+Th1 and CD4+Th17 cells to the detriment of the regulatory profile mediated by regulatory T cells (CD4+Treg). The balance between Treg and Th17 cells is critical for fetal tolerance and disease prevention. Molecules called immune checkpoints, or biomolecules with negative regulatory activity, are expressed mainly in Treg cells and are considered responsible for the balance between pro and anti-inflammatory signals, which occur at the maternal-fetal interface to ensure maternal tolerance and pregnancy success. The present project aims to evaluate the expression of the anti-inflammatory biomarkers PD-1, CTLA-4, GITR, TIGIT, and CD155 by regulatory T cells (CD4+/FoxP3+) in peripheral blood in pregnant women with pre-eclampsia and in normotensive pregnant women, and its association with TNFR2 expression in regulatory T cells. Forty pregnant women will be evaluated, 20 with preeclampsia and 20 normotensive, matched by gestational age. The blood collected from these pregnant women will be centrifuged, the plasma separated and stored at -80°C for measurement of cytokines TNF-alpha, IL-17, IL-10, and TGF-beta, and soluble receptors PD-1, CTLA-4, CD155, GITR, and TNFR2 by ELISA technique. The determination of the intracytoplasmic transcription factors RORgt (Th17) and Foxp3 (Treg) and the expression of PD-1, CTLA-4, CD155, GITR, and TNFR2 in the membrane of T cell subpopulations will be performed by flow cytometry, using specific monoclonal antibodies, labeled with fluorochromes soon after blood collection (endogenous expression). The results will be analyzed using parametric or non-parametric tests at a significant level of 5%.