Background/Purpose: Effects of environmental exposures on the development of systemic lupus erythematosus (SLE) are potentially important and relatively unexplored in SLE pathogenesis. An excess of reported SLE cases in a community surrounding a former uranium ore processing plant provided an opportunity to evaluate the relationship between uranium exposure through downstream air or water and SLE. Our specific a priori objective was to explore the hypothesis that SLE patients will be found more frequently in community members exposed to high prior uranium exposure levels in the Fernald Community Cohort (FCC).

Methods: A nested case control study was performed with data from the FCC. The FCC is comprised of voluntarily enrolled individuals who lived during plant operation within 5 miles of a uranium ore processing facility in Fernald, OH and followed from 1990 to 2008, which was after the plant ceased operations. No uranium plant workers are included in this study. Potential SLE cases were identified with searches for ICD9 codes associated with lupus (710.0 and 695.4) and a medication code search for hydroxychloroquine. Sera from potential cases were screened for autoantibodies using the Bioplex 2200 multiplex assay and anti-cardiolipin antibodies using ELISA. Cases were confirmed using an operational definition that included American College of Rheumatology classification criteria and medical record documentation. Four age-, race-, and sex-matched controls were selected for every case. Cumulative uranium exposure was calculated for each individual with a dosimetry model developed by the Centers for Disease Control and Prevention. Covariates in the analysis included smoking history, alcohol intake history, and family history of SLE. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). For comparison, preliminary analysis with rheumatoid arthritis (RA, ICD9 code 714.0) was also performed.

Results: The FCC includes 4,187 individuals with low uranium exposure, 1,273 with moderate exposure, and 2,756 with high exposure. SLE was confirmed in 20 of 26 cases with an ICD9 code of 710.0, in 2 of 5 cases with an ICD9 code of 695.4, and in 2 of 43 other cases prescribed hydroxychloroquine. The female to male ratio among cases was 5 to 1. Of the SLE cases, 5 were in the low exposure group, 7 in the moderate exposure group, and 12 in the high exposure group. Following logistic regression modeling, SLE was found to be associated with high exposure (OR 4.81, 95% CI 1.38-16.75, p = 0.043). There was no association between low or moderate uranium exposure and SLE. In the FCC overall, RA occurs at the expected prevalence, while SLE is increased by 5-fold over the expected prevalence.

Conclusion: High uranium exposure is associated with SLE relative to matched controls in this sample of uranium exposed individuals, suggesting that our hypothesis is correct. Potential explanations for this relationship include the estrogen effects of uranium, somatic mutation from ionizing radiation, or effects of some other unidentified accompanying exposure. Whatever the cause for this association, understanding the basis of this relationship is likely to provide important fundamental insight into SLE pathogenesis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identifying-a-link-between-uranium-exposure-and-systemic-lupus-erythematosus-in-a-community-living-near-a-uranium-plant/