Background/Purpose:

Environmental exposures may play a substantial role in the pathogenesis of SLE. The goal of this study is to characterize the serum levels of multiple chemicals in a cohort of SLE patients and controls.

Methods:

Patients from the California Lupus Epidemiology Study and healthy controls were studied. Banked serum was analyzed by Liquid Chromatography Quadruple Time-of-Flight Mass Spectrometry (LC-QTOF/MS). The results of the LC-QTOF/MS analysis were matched into a database of 740 potentially detected environmental organic chemicals. Detection frequencies of chemicals were calculated. Univariate and multivariate analyses were performed, adjusting for potential confounders. Association testing between chemical classes, chemicals and specific lupus phenotypes and disease activity was performed.

Results:

58 females with SLE and 78 healthy females were studied. The number of unique chemicals detected was 309, with an average of 60 chemical-hit matches per subject (range 32-150). SLE patients had a higher detection frequency of phthalates whereas healthy controls had a higher detection frequency of pesticides and phenols (table 1). A higher phthalate detection frequency was associated lupus nephritis, but did not correlate with disease activity (SLEDAI score), hypocomplementemia or anti ds-DNA status. In patients with SLE, a per count increase in detection frequency of a phthalate was associated with an OR of 1.4 for history of lupus nephritis, adjusting for age, disease duration, race, education and income (p=0.002, CI[1.1-1.7]). Chemicals detected at a higher frequency in SLE were enriched for specific phthalates such as metabolites of DHEP (table 2). Among SLE patients, 2 specific phthalates, mono2ethyl5oxohexylphthalate (p=0.00002) and mono2ethyl5oxohexylphthalate (p=0.00015) were associated with lupus nephritis.

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 significantly increased exposure to phthalates compared to healthy controls, with further enrichment among patients with lupus nephritis. Exposure to Mono-(2-carboxymethylhexyl) phthalate has been associated with dsDNA production and lupus nephritis in NZB/W F1 mice.