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. 2024 Jun;76(6):905-918.
doi: 10.1002/art.42779. Epub 2024 Mar 7.

Screening of Environmental Chemicals to Characterize Exposures in Participants With Systemic Lupus Erythematosus

Cristina M Lanata  1 , Kimberly E Taylor  2 , James Hurst-Hopf  3 , Joanne Nititham  1 , Ashira Blazer  4 , Laura Trupin  2 , Patricia Katz  2 , Maria Dall'Era  2 , Jinoos Yazdany  2 , Sharon A Chung  2 , Dimitri Abrahamsson  5 , Roy Gerona  2 , Lindsey A Criswell  1
Affiliations

Screening of Environmental Chemicals to Characterize Exposures in Participants With Systemic Lupus Erythematosus

Cristina M Lanata et al. Arthritis Rheumatol. 2024 Jun.

Abstract

Objective: There is a need to characterize exposures associated with the pathogenesis of systemic lupus erythematosus (SLE). In this pilot study, we explore a hypothesis-free approach that can measure thousands of exogenous chemicals in blood ("exposome") in patients with SLE and unaffected controls.

Methods: This cross-sectional study analyzed a cohort of patients with prevalent SLE (n = 285) and controls (n = 106). Plasma was analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Mass spectrometry features present in at least 25% of all samples were selected for association analysis (n = 2,737). Features were matched to potential chemicals using available databases. Association analysis of abundances of features with SLE status was performed, adjusting for age and sex. We also explored features associated with SLE phenotypes, sociodemographic factors, and current medication use.

Results: We found 30 features significantly associated with SLE status (Bonferroni P < 0.05). Of these, seven matched chemical names based on databases. These seven features included phthalate metabolites, a formetanate metabolite, and eugenol. The abundance of acid pesticides differed between patients with SLE and controls (Bonferroni P < 0.05). Two unmatched features were associated with a history of lupus nephritis, and one with anti-double-stranded DNA antibody production (Bonferroni P < 0.05). Seventeen features varied by self-reported race and ethnicity, including a polyfluoroalkyl substance (analysis of variance P < 1.69 × 10-5). Eleven features correlated with antimalarials, 6 with mycophenolate mofetil, and 29 with prednisone use.

Conclusion: This proof-of-concept study demonstrates that LC-QTOF/MS is a powerful tool that agnostically detects circulating exogenous compounds. These analyses can generate hypotheses of disease-related exposures for future prospective, longitudinal studies.

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Figures

Fig 1.
Fig 1.
Analysis pipeline to characterize plasma environmental chemicals in SLE and control participants
Fig. 2
Fig. 2
Boxplots of matched features grouped into chemical classes in SLE vs unaffected controls.
Fig 3.
Fig 3.. Heatmap of 49 selected features according to association analyses.
Abundances of features were normalized, and natural log transformed.
See this image and copyright information in PMC

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