A Comprehensive Method to Study Environmental Chemicals in Serum in Patients with SLE

Cristina Lanata¹, Kim Taylor², James Hurst-Hopf¹, Laura Trupin¹, Patricia Katz³, Jinoos Yazdany¹, Maria Dall'Era⁴, Dimitri Abrahamsson¹, Lindsey Criswell⁵ and Roy Gerona¹, ¹UCSF, San Francisco, CA, ²University of California, San Francisco, San Francisco, CA, ³University of California, San Francisco, Novato, CA, ⁴Division of Rheumatology, University of California, San Francisco, CA, ⁵Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, University of California San Francisco, San Francisco, CA

Meeting: ACR Convergence 2020

Keywords: Environmental factors, Systemic lupus erythematosus (SLE)

Session Information

Date: Monday, November 9, 2020

Session Title: SLE – Diagnosis, Manifestations, & Outcomes Poster III: Bench to Bedside

Session Type: Poster Session D

Session Time: 9:00AM-11:00AM

Background/Purpose: Environmental exposures may play a substantial role in the pathogenesis of Systemic Lupus Erythematosus (SLE), however it has been challenging to measure and capture relevant exposures in a comprehensive manner. The goal of this study is to develop a novel method to characterize the serum levels of circulating environmental chemicals and metabolites in a well-characterized cohort of SLE patients and controls.

Methods: Participants from the California Lupus Epidemiology Study (CLUES), a longitudinal cohort of individuals with rheumatologist-confirmed SLE were included (n=332). A cohort of healthy individuals matched by age, ethnicity and sex was recruited (n=100). Serum was analyzed by liquid chromatography quadruple time-of-flight Mass Spectrometry (LC-QTOF/MS). Feature detection, peak alignment, and abundance normalization using internal standards was performed using Agilent Mass Profiler and adjusted for batch effects using ComBat¹.Principal Components Analysis was used to assess batch adjustment and correct for residual batch effects. Compounds detected in at least 25% of participants were selected for association testing between chemical abundances and SLE status. We analyzed differences between cases and controls using linear models of feature abundances, adjusting for censoring below the detection limit, residual batch effects, and covariates age, sex, and ethnicity. Results of potential detected environmental chemicals were matched into a curated database of hazardous environmental chemicals.

¹Johnson et al, Biostatistics. 2007; 8(1):118–27

Results: We detected 66,861 features in our cohort; with 3,192 present in at least 25% of samples and analyzed for association with case status. Out of the 3192 features, 70 were significantly different, including 4-Hexyloxyphenol and 39 additional formula-matched compounds.

Conclusion: LC-QTOF/MS can identify a wider range of potential chemical exposures in SLE, and may aid in prioritizing chemicals for further research and intervention. We found that patients with SLE had different chemicals and endogenous metabolites compared to healthy controls.

Disclosure: C. Lanata, None; K. Taylor, None; J. Hurst-Hopf, None; L. Trupin, None; P. Katz, None; J. Yazdany, Eli Lilly, 5, Astra Zeneca, 5; M. Dall'Era, Janssen, 5, AstraZeneca, 5; D. Abrahamsson, None; L. Criswell, None; R. Gerona, None.

To cite this abstract in AMA style:

Lanata C, Taylor K, Hurst-Hopf J, Trupin L, Katz P, Yazdany J, Dall'Era M, Abrahamsson D, Criswell L, Gerona R. A Comprehensive Method to Study Environmental Chemicals in Serum in Patients with SLE [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/a-comprehensive-method-to-study-environmental-chemicals-in-serum-in-patients-with-sle/. Accessed November 28, 2020.

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