Association of Systemic Lupus Erythematosus With Uranium Exposure in a Community Living Near a Uranium‐Processing Plant: A Nested Case–Control Study

Abstract

Objective Explore the hypothesis that cases of SLE will be found more frequently in community members with high prior uranium exposure in the Fernald Community Cohort (FCC). Methods A nested case control study was performed. The FCC is a volunteer population that lived near a uranium ore processing plant in Fernald, Ohio, USA during plant operation and members were monitored for 18 years. Uranium plant workers were excluded. SLE cases were identified using American College of Rheumatology classification criteria, laboratory testing, and medical record review. Each case was matched to four age-, race-, and sex-matched controls. Sera from potential cases and controls were screened for autoantibodies. Cumulative uranium particulate exposure was calculated using a dosimetry model. Logistic regression with covariates was used to calculate odds ratios (OR) with 95% confidence intervals (CI). Results The FCC includes 4,187 individuals with background uranium exposure, 1,273 with moderate exposure, and 2,756 with higher exposure. SLE was confirmed in 23 of 31 individuals with a lupus ICD9 code, and in 2 of 43 other individuals prescribed hydroxychloroquine. The female:male ratio was 5.25:1. Of the 25 SLE cases, 12 were in the higher exposure group. SLE was associated with higher uranium exposure (OR 3.92, 95% CI 1.131-13.588, p = 0.031). Conclusion High uranium exposure is associated with SLE relative to matched controls in this sample of uranium exposed individuals. Potential explanations for this relationship include possible autoimmune or estrogen effects of uranium, somatic mutation, epigenetic effects, or effects of some other unidentified accompanying exposure.

Minimal uranium immunotoxicity following a 60-day drinking water exposure to uranyl acetate in male and female C57BL/6J mice

“…Multiple studies in human populations report evidence of immunotoxicity in human populations chronically exposed to U. Exposure to elevated levels of U was found to be associated with increased incidence of systemic lupus erythematosus in a cohort of individuals living near a U processing plant (Lu-Fritts et al, 2014). Recent findings from Erdei et al, (2019), indicate elevation of serological autoantibodies in Native Americans living in close proximity to abandoned uranium mine wastes sites.…”

“…Many of these rural communities rely on unregulated drinking water sources (i.e., well water) that exceed the United States Environmental Protection Agency and World Health Organization maximum contaminant level for U of 30 ppb (US EPA 2006;WHO 2012;deLemos et al, 2009;Hoover et al, 2017). As a result, many people in this region are chronically exposed to U at levels that have been linked to a multitude of detrimental health outcomes, including immune dysfunction (Lu-Fritts et al, 2014;Lourenço et al, 2013;and Erdei et al, 2019). In particular, data from Native American populations living in close proximity to abandoned mine waste sites indicate a correlation between uranium and other metal exposures and the presence of serological indicators of autoimmunity (i.e., increased prevalence of anti-nuclear antibodies) (Erdei et al, 2019;Ong et al, 2014).…”

Inhibition of poly(ADP-ribose)polymerase-1 and DNA repair by uranium

“…Many of these abandoned waste sites are located on or in proximity to Native American lands in the West where existing disparities in health raise additional concern of vulnerability to environmental toxicant insults. Studies by our group and others have indicated that community members living in proximity to uranium contaminated sites have an increased likelihood of developing chronic diseases including hypertension, kidney disease, and diabetes (Wagner et al, 2010; Hund etal., 2015); as well as immune dysfunction and autoimmunity (Lewis, 2013; Lu-Fritts et al, 2014). Our research group has also found that urine uranium concentrations within the Navajo population are greater than the national norms, underscoring the need for additional studies within these exposed communities (Lewis, 2013).…”

Understanding the role of environmental factors in the development of systemic lupus erythematosus

“…A recent case-control study suggested an association of SLE with residential proximity to a uranium processing plant [64]. Two case-control studies have shown elevated risk of SLE associated with self-reported exposure to mercury [55,56].…”