Investigating the impact of the exposome in patients developing autoimmune diseases

(2025)

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Abstract
Autoimmune diseases (AIDs) are complex and multifactorial conditions involving a breakdown in immune tolerance and chronic inflammation. In addition to genetic predisposition, environmental factors, such as trace metal exposure, are increasingly recognized as potential contributors to immune dysregulation. Prior studies have shown that both essential and non-essential metals can modulate immune function, either by impairing regulatory pathways or promoting pro-inflammatory responses. This master’s thesis was conducted within the framework of the European H2020 Eximious project, which aims to better understand the role of environmental exposure in human health using a biomonitoring-based approach. The study focuses on two systemic AIDs, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and investigates whether urinary concentrations of 24 trace metals are associated with an increase in circulating cytokine profiles. A total of 302 participants were recruited, including patients with RA (n = 99), SLE (n = 77) and healthy controls (n = 110). Urinary metal concentrations were measured using ICP-MS and plasma cytokines were quantified via the Olink Target 48 Cytokine panel. Statistical analyses included descriptives statistics, one-way ANOVA and multiple linear regression models adjusted for potential confounding variables such as age, sex, BMI and smoking status. The analyses showed that urinary concentrations of Cd, Al, Pb and Cu were significantly higher in RA and/or SLE patients compared to controls. Differences in cytokine levels were also observed between the cohorts. In some cases, statistical associations were found between specific metals and cytokines involved in immune regulation. These results do not allow for causal conclusions but suggest that metal exposure may be linked to changes in immune activity in autoimmune diseases. This study contributes to a better understanding of the interactions between environmental exposure and immune markers and raises new questions about the role of metals in the context of autoimmunity.