INFLUENCE OF EXPOSURE TO INHALABLES FINE PARTICLES ON DNA METHYLATION PROFILE IN CHILDREN AND ADOLESCENTS WITH JUVENILE SYSTEMIC LUPUS ERYTHEMATOSUS

• Grant number: 23/12748-1
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2025
• End date: July 31, 2027
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Lucia Maria Mattei de Arruda Campos
• Grantee: Lucia Maria Mattei de Arruda Campos
• Host Institution: Instituto da Criança Professor Doutor Pedro de Alcantara (ICR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Adriana Maluf Elias ; Clovis Artur Almeida da Silva ; Katia Tomie Kozu ; Leslie Domenici Kulikowski ; Mariana Matera Veras ; Patricia Palmeira Daenekas Jorge ; Paulo Hilário Nascimento Saldiva ; Sylvia Costa Lima Farhat

Abstract

Air pollution remains an important environmental factor that impairs human health. According to the World Health Organization, about seven million people die each year from exposure to air pollutants. Most of the deleterious effects resulting from exposure to air pollution on human health have been associated with particulate matter (PM), including particles smaller than 2.5 ¼m (fine particles- PM2.5) and 0.1 ¼m in diameter (ultrafine particles: PM0.1).Studies have shown associations between exposure to air pollution and onset/aggravation of systemic lupus erythematosus. In children and adolescents with lupus, studies have shown associations between exposure to fine particles and increased risk of moderate to severe disease activity and increased risk of nephritis. Association between exposure to fine particles and decreased serum levels of C3 complement and increased levels of serum concentrations of interleukins (TNF-alpha, IL-10, IL-17 and IFN-alpha) have also been reported.The three main epigenetic mechanisms associated with systemic diseases are: DNA methylation, histone modifications and non-coding RNA expression. Changes in all three mechanisms have been related to lupus and also to exposure to inhalable fine and ultrafine particles, but to our knowledge, only two studies in adults have evaluated the influence of exposure to air pollutants on the epigenetics of lupus patients. In the pediatric population, we did not find studies published in this regard in the medical literature.Thus, this study aims to evaluate the influence of PM2.5 exposure on the DNA methylation profile in patients with juvenile systemic lupus erythematosus with and without nephritis. The hypothesis is that exposure to inhalable fine particles can modify the global methylation profile of genomic DNA and genes related to juvenile systemic lupus erythematosus (JSLE) activity, especially lupus nephritis.Cross-sectional studyMain objective- To evaluate the DNA methylation profile in peripheral blood neutrophils in promoter regions of key genes linked to cytokines and chemokines; nephritis-related genes; Interferon-regulated genes in JSLE patients, with and without nephritis, and healthy children and adolescentsSpecific objective - To evaluate the influence of exposure to air pollution in the period of 7, 14, 21 and 30 days prior to blood sample collection on the DNA methylation profile in peripheral blood neutrophils in promoter regions of key genes linked to cytokines and chemokines; nephritis-related genes; Interferon-regulated genes in JSLE patients, with and without nephritis, and healthy children and adolescentsParticipation in this study will be offered to participants during a workshop by ICr-HC-FMUSP that will be held on the World Lupus Day, on May 10, 2023.The genome wide association study (GWAS) will be used to identify genetic signatures associated with phenotypic traits of the disease in question (lupus). Thus, patients with lupus with and without nephritis and healthy children and adolescents will be evaluated. The use of this last group is important to verify if the DNA methylation alterations found in JSLE patients do not occur in the healthy population. After acceptance to participate and the consent process of the parents and children and adolescents is completed, a clinical evaluation will be carried out and a sample of 5 to 10 mL of blood will be collected for the separation of neutrophils in VD Vacutainer tubes containing EDTA as an anticoagulant stored in refrigeration and forwarded within 72 hours to the cytogenomics laboratory to perform the neutrophil separation, DNA extraction with subsequent freezing at minus 80 degrees Celsius. The methylation assay and the bioinformatics analyzes will be carried out in the cytogenomics and molecular pathology laboratory of the LIM 03 of the HCFMUSP of the pathology department belonging to the Multiuser Equipment Network Program (PREMiUM) of the HC-FMUSP. (AU)