Per- and polyfluoroalkyl substances (PFASs) are emerging environmental contaminants that have been used since the 1940s. PFASs, due to their surfactant properties and chemical stability, have found many applications in industry as well as in the consumer sector. (1) Due to their high stability, PFASs persist in the environment and thus can be found in water, soil, and air. Therefore, people and other living organisms are continuously exposed to these chemicals. (2) Alarmingly, PFASs have been found in human matrices with high frequency. The United States of America (U.S.A.) and European epidemiological and biomonitoring studies report that PFASs are present in human blood, often with a detection frequency above 90%. (3,4)

PFAS exposure has been associated with adverse health outcomes, such as liver damage, endocrine disruption, liver and testicular cancer, and immune disruption. (5) Suppressed antibody response after vaccination is one of the frequently described effects of the immune disruption associated with PFASs. (6,7) Further, PFAS exposure has been associated with an increased risk of infectious diseases, the prevalence of asthma, and altered immunological responses in allergies. (7) Taken together, it is evident that PFASs are immunomodulatory stressors; however, the mechanism of action has still not been fully elucidated, specifically in humans.

A number of epidemiological studies have indicated that PFASs interfere with antibody production. Experimental studies reviewed recently by Ehrlich et al. in 2023 suggest the involvement of nuclear receptors, such as NF-?B and PPARs, and/or calcium signaling. (8) Data from both epidemiological and toxicological studies are valuable for determining adverse outcome pathways (AOPs), i.e., the set of casually linked events leading from the initial molecular event to the apical health effect. Especially, the identification and quantification of biomarkers of effect provide valuable data for building AOPs. (9) By implementing omics and advanced bioinformatics, biomarkers of effect on biological levels such as the genome, transcriptome, proteome, and metabolome can be revealed. These omics technologies are useful for characterizing the effect of PFASs on human health and, most importantly, revealing an early event that may lead to adverse health effects. (10,11) Genome-wide transcriptomic analysis of immune blood cells, for example, can uncover valuable information about complex immune signaling. This technique allows researchers to analyze the complete set of ribonucleic acid (RNA) transcripts present in cells, providing valuable insights into the gene expression patterns underlying immune responses...

...the objective of this study was to identify a transcriptomic response that is conserved for multiple PFASs, including the seven most abundant ones: perfluoropentanoate (PFPA), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), pefluorohexanesulfonate (PFHxS), and perfluorooctanesulfonate (PFOS). To reach this aim, the gene expression profiles within human immune cells in relation to PFAS blood levels from a cross-sectional Czech adult cohort study were researched. Using this approach, we aimed to uncover the molecular responses underlying PFAS-associated immunomodulation in humans. Through the utilization of transcriptomics, our research endeavors shed light on the specific gene expression patterns, molecular pathways, and regulatory mechanisms involved in the immune system’s response to PFAS exposure.

Taken together, the results of the current study indicate that multiple PFAS exposure influences the immune system in the phase of late B cell development, specifically B cell activation, GC reactions, and plasma cell development. As GCs and plasma cells are essential for antibody production, the findings of the current study are in line with suppressed antibody responses after vaccination associated with PFAS exposure, which has been largely reported in the literature. (6,56?60)