D3.375 - The impact of strontium exposure on allergic rhinitis development via IRE1-mediated protein expression: ECHO-COCOA study

Health impacts are becoming a concern when high concentrations of trace elements are exposed to the environment. Strontium (Sr) has recently emerged as one of the substances of concern, with a growing association with the development of allergic diseases. This study aimed to investigate the mechanisms underlying the association between Sr exposure and allergic rhinitis through transcriptome analysis.

Data from 531 subjects in the ECHO-COCOA study were analyzed. AR was defined by physician diagnosis at 7-12 years of age. Strontium levels were measured in urine at 6-7 years old. Serum total and specific IgE, blood eosinophil counts, and cytokine levels (IL-2, IL-6, and IL-5) were investigated at 6-7 years old. The subjects (n=69) were divided into four groups based on Sr levels and the presence of AR and pathway enrich analysis was performed. 

Sr levels were higher in children with AR than those without AR (p=0.001). Significant correlations were found between Sr levels and total IgE levels, as well as blood eosinophil counts (r=0.12, p=0.014; r=0.11, p=0.022, respectively). Serum IL-5 levels were significantly elevated in the group with high Sr exposure and AR compared to the group with low Sr exposure without AR (p=0.006). Additionally, in the low Sr-AR group, the neutrophil response was found to be the main mechanism, whereas, in the high Sr-AR group, the IRE1-mediated unfolded protein response and related protein expression/regulation in the ER protein response pathway were identified as the predominant mechanism.

Sr exposure affects AR in children and induces a ROS response, leading to ER stress and IRE1-mediated regulation of protein expression, which triggers immune responses and contributes to the development of AR.