Air Pollution and Polyclonal Elevation of Serum Free Light Chains: An Assessment of Adaptive Immune Responses in the Prospective Heinz Nixdorf Recall Study

BACKGROUND: Residential exposure to air pollution (AP) has been shown to activate the immune system (IS). Although innate immune responses to AP have been studied extensively, investigations on the adaptive IS are scarce. OBJECTIVES: The aim of this study was to investigate the association between short- to long-term AP exposure and polyclonal free light chains (FLC) produced by plasma cells. METHODS: We used repeated data from three examinations ([Formula: see text]: 2000–2003; [Formula: see text]: 2006–2008; and [Formula: see text]: 2011–2015) of the population-based German Heinz Nixdorf Recall cohort of initially 4,814 participants (45–75 y old). Residential exposure to total and source-specific particulate matter (PM) with an aerodynamic diameter of 10 or [Formula: see text] ([Formula: see text] and [Formula: see text] respectively), nitrogen dioxide ([Formula: see text]), and particle number concentrations (accumulation mode; [Formula: see text]) was estimated using a chemistry transport model with different time windows (1- to 365-d mean ± standard deviation) before blood draw. We applied linear mixed models with a random participant intercept to estimate associations between total, traffic- and industry-related AP exposures and log-transformed FLC, controlling for examination time, sociodemographic and lifestyle variables, estimated glomerular filtration rate and season. RESULTS: Analyzing 9,933 observations from 4,455 participants, we observed generally positive associations between AP exposures and FLC. We observed strongest associations with middle-term exposures, e.g., 3.0% increase in FLC (95% confidence interval: 1.8%, 4.3%) per interquartile range increase in 91-d mean of [Formula: see text] ([Formula: see text]). Across the different pollutants, [Formula: see text] showed strongest associations with FLC, followed by [Formula: see text] and [Formula: see text]. Effect estimates for traffic-related exposures were mostly higher compared with total exposures. Although [Formula: see text] and [Formula: see text] estimates remained stable upon adjustment for PM, PM estimates decreased considerably upon adjustment for [Formula: see text] and [Formula: see text]. DISCUSSION: Our results suggest that middle-term AP exposures in particular might be positively associated with activation of the adaptive IS. Traffic-related PM, [Formula: see text] , and [Formula: see text] showed strongest associations. https://doi.org/10.1289/EHP7164