Screening of environmental chemicals to characterize exposures in participants with Systemic Lupus Erythematosus

Abstract

ObjectiveThere 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.MethodsThis cross‐sectional study analyzed a cohort of prevalent SLE cases (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 utilizing 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.ResultsWe found 30 features significantly associated with SLE status (Bonferroni p<0.05). Of these, 7 matched chemical names based on databases. These seven features included phthalate metabolites, a formetanate metabolite, and eugenol. The abundance of acid pesticides differed between SLE cases 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 (ANOVA p < 1.69E‐05). Eleven features correlated with antimalarials, 6 with mycophenolate mofetil, and 29 with prednisone use.ConclusionThis 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.image