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Participation of NETs as a biomarker of autoimmune rheumatic diseases

Grant number: 22/08052-9
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): August 01, 2022
Effective date (End): July 31, 2024
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:Paulo Louzada Junior
Grantee:Gabriela Torres Rebech
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID


Rheumatoid arthritis (RA) is an inflammatory, systemic, chronic and autoimmune disease characterized by synovial hyperplasia and joint destruction. Currently, etiopathogenesis of RA have focused on importance of neutrophils and the anti-apoptotic mechanisms of innate immune response cells. There are several mechanisms which neutrophils can promote immune dysregulation in RA and lead to loss of immune tolerance, synovial inflammation, initiation and perpetuation of RA, and the development of Anti-Citrullinated Peptide Antibodies (ACPAs) commonly seen during RA. Neutrophils have a particular type of cell death through the formation of neutrophil extracellular traps (NETs), named NETosis. NETs are unfolded chromatin strands, composed of DNA and histones, and coated with antimicrobial granules whose biological function is to help fight bacterial infection. During NET formation, myeloperoxidase mediates the release of proteases granules such as neutrophil elastase that translocate to nucleus, where they cleave histones and promote chromatin decondensation. The enzyme peptidyl arginine deiminase 4 (PAD-4), also located in the nucleus, citrullinizes histones during NET formation, potentially promoting further decondensation of genetic material. If this process occurs unregulated or if the clearance of NETs is reduced, it can lead to autoimmunity, tissue damage and thrombosis. In patients with active RA, there is a large formation of NETs and this may be related to loss of immunological tolerance. Therefore, understanding the participation of NETs in RA etiopathogenesis becomes necessary, because characterization of pathways involved in NETs development may have potential application in pharmacological strategies to block the NETs formation and secretion of cytokines by neutrophils, as well as in biomarkers determination for RA diagnostic, favoring therapeutic decisions and, consequently, the patient's prognosis. (AU)

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