Selection of Rapid Protocols for Diagnostic Confirmation of Patients with Autoinflammatory Syndromes CAPS

• Grant number: 24/23297-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Alessandra Pontillo
• Grantee: Jéssica Antunes Ribeiro
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 23/17878-0 - Evaluation of Inflammasome Activation in Cells of Patients with Autoinflammatory Disease and Its Correlation with Individual Genetics, AP.R

Abstract

Periodic Syndromes Associated with Cryopyrin (CAPS) are monogenic inflammasomopathies, meaning systemic autoinflammatory diseases caused by gain-of-function mutations in the NLRP3 gene. This gene encodes the NLRP3 inflammasome receptor, and its mutations lead to hyperactivation of the complex and increased production of inflammatory cytokines IL-1¿ and/or IL-18, as well as the induction of pyroptosis, resulting in periodic or chronic systemic inflammation, with a heterogeneous clinical phenotype among patients.Although genetic testing is crucial for confirming the diagnosis, it is not always conclusive or informative regarding phenotypic variability, prognosis, and treatment response, and in middle- and low-income countries like Brazil, it is not accessible to the entire population. This justifies the efforts of several research groups to develop functional tests that assist in clinical diagnosis and the characterization of mutations and new variants.In this project, we propose testing various NLRP3 activation protocols in leukocytes isolated from peripheral blood, aiming to identify the best sample type (PBMCs, monocytes, monocytes-derived macrophages) and stimulus for identifying patients with CAPS. The ability to discriminate between "classic" and "non-classic" patients, the protocol execution time, and the cost/benefit will be considered in selecting the best tool.