Associations of perfluoroalkyl substances with proteomic biomarkers of inflammation

Abstract

PDS 62: Chemicals and metals: exposure and biomarkers, Johan Friso Foyer, Floor 1, August 28, 2019, 10:30 AM - 12:00 PM Background: Perfluoroalkyl substances (PFAS) have been linked to immunotoxicity in experimental studies. Although PFAS exposure is associated with altered immune function in epidemiological studies of children, it is less known whether these findings also hold for adults or elderly individuals. Methods: We measured a panel of 92 proteins in plasma from 965 elderly individuals from Sweden (all aged 70, 50% women) using a multiplex proximity extension assay including, among others, immune-related markers such as tumor necrosis factors, interleukins as well as cardiometabolic markers such as monocyte chemoattractant proteins. Plasma PFAS concentrations were determined using isotope-dilution ultra-pressure liquid chromatography coupled to tandem mass spectrometry. We examined associations using adjusted multivariable linear regression. Results: Of the 86 protein markers passing quality control and detection frequency >75%, 20 were negatively associated with levels of five PFAS following adjustment for sex, sample storage time in freezer, and correction for multiple testing. Associations of some PFAS and hepatocyte growth factor (HGF), macrophage colony-stimulating factor 1 (CSF-1), and tumor necrosis factor receptor 1 (TNF-R1) remained significant following further adjustment for smoking, exercise habits, education, energy, and alcohol intake. In this case, plasma concentrations of perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were inversely associated with HGF (βPFHxS: -0.11: 95% confidence interval (CI); -0.17, -0.06; βPFDA: -0.07: 95% CI; -0.10, -0.04, and βPFUnDA: -0.07: 95% CI; -0.11, -0.04). PFUnDA was further inversely associated with CSF-1 (β: -0.09: 95% CI; -0.12, -0.06) and TNF-R1 (β: -0.07: 95% CI; -0.10, -0.04). Conclusions: Our findings implicate PFAS exposure with decreased plasma inflammatory markers and require replication in larger studies.