Impact of PFAS exposure on immune-mediated diseases and immune transcriptome in Czech adults

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) are emerging environmental contaminants with multiple hazardous properties including immunomodulation potency. We aimed to investigate 1) the association between PFAS exposure and immune-mediated diseases (IMDs) and 2) the expression of genes associated with PFAS exposure in a population of Czech adults. METHODS: This study involved 309 adults from the Czech CELSPAC:YA cohort. The associations of serum concentrations of 9 PFAS with 9 IMDs were assessed by logistic regression. Furthermore, Bayesian kernel machine regression (BKMR) was used to estimate the effect of the PFAS mixture on IMDs. In cases of a statistically significant interaction of PFASs and sex, sex-stratified analyses were performed. To identify transcriptomic profiles, isolated RNA from peripheral mononuclear blood cells was sequenced (QuantSeq) and analysed. Significantly expressed genes associated with multiple PFASs (at least with 4 PFASs) were employed for enrichment analysis by Pathway Studio. All analyses were adjusted for relevant confounders (i.e., sex, age, BMI, smoking, education, and family history of IMDs). RESULTS: PFOA, PFOS, and PFUnDA were negatively associated with allergies. Similarly, BKMR modeling showed a negative tendency in the overall effect of PFAS mixture on IMDs. Results of the stratified analysis suggest sex to be an effect modifier in the association of PFOS and atopic eczema. Regarding transcriptomic analysis, 166 statistically significant genes were associated with multiple PFAS exposure. Enrichment analysis of these genes showed involvement of B cell signaling, specifically mechanisms involved in the production of antibody-secreting plasma cells. CONCLUSIONS: Our results contribute to the body of literature that observes the immunomodulatory effect of PFAS exposure on the level of disease prevalence and further brought new information about underlying deregulatory mechanisms. KEY MESSAGES: • Our study showed an immunosuppressive effect of PFAS exposure on the level of prevalence of immune-mediated diseases, both for PFASs individually and as a mixture. • Genome-wide transcriptomic analysis revealed the involvement of plasma cells as a potential key event of PFAS-induced immunomodulation.