Background:Black individuals with systemic lupus erythematosus (SLE), who are predominantly women, have disproportionately poorer health outcomes across the trajectory of their disease including increased mortality, higher symptom burden, and poor quality of life than non-Hispanic Whites. The heterogeneity of immunopathology and biochemical complexity of SLE create major knowledge gaps around the mechanisms of disease and differences in SLE symptom expression. Metabolomics may reveal biochemical dysregulation that underlies SLE symptoms and provide novel metabolic targets for precision symptom interventions.Objectives:We conducted untargeted metabolomic plasma profiling of Black females with SLE and Black female non-SLE controls to gain insight into metabolic disturbances associated with SLE.Methods:We analyzed blood specimens collected from 23 Black female patients with diagnosis of SLE during a routine outpatient rheumatology visit and from 21 Black female non-SLE controls whose data were collected as part of another study of obese caregivers. Data collection for both cases and controls was completed with harmonized protocols. Clinical data for cases were obtained via chart review and both cases and controls completed identical, reliable and valid measures of fatigue, depression, anxiety, and sleep disturbance. A commercial metabolomics analysis company within the US conducted untargeted metabolomics on the 44 plasma samples using ultrahigh performance liquid chromatography/tandem mass spectrometry along with metabolite identification and quantification to examine differences between SLE/non-SLE groups.Results:All SLE subjects met 2019 EULAR/ACR criteria (Aringer et al., 2019). SLE subjects were significantly (p < .05) younger (42.5 ± 12.2 vs. 63.2 ± 6.4), had a lower BMI (30.3 ± 9.4 vs. 34.9 ± 4.1), and greater co-morbidities (2.3 ± 1.3 vs. 1.1 ± 1.3) than non-SLE controls. SLE subjects reported higher symptoms than controls across all measures, but differences were not statistically significant. Metabolomics analysis revealed 290 biochemicals that were statistically significant (p ≤ .05) between SLE and non-SLE groups. Random Forest analysis had a predictive accuracy of 91% in differing between the two groups using out-of-bag sampling. Significant metabolic differences between groups were noted in biochemicals associated with glycolysis, the TCA cycle (see Table 1), fatty acid metabolism, branched chain amino acids, sterol levels, heme catabolism, and potential markers of renal impairment. Overall, the differences would suggest reduced energy production among SLE patients compared to controls.Conclusion:Black women with SLE had biochemical profiles consistent with reduced energy production which has implications for the high burden of fatigue and other symptoms in this population. Future work with larger sample sizes should involve integrating symptom and metabolomics data to identify potential biomarkers of symptom burden.References:Aringer, M., Costenbader, K., Daikh, D. et al. (2019). 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis, 78,1151-1159.Acknowledgements:This work was supported by a research re-entry supplement to L. Kimble under the parent award 1P30NR018090-02S1 Center for the Study of Symptom Science, Metabolomics, and Multiple Chronic Conditions (Song, PI) funded by the National Institute of Nursing Research, National Institutes of Health, USA.Disclosure of Interests:Laura P. Kimble: None declared, Arezou Khosroshahi Consultant of: Have received honorarium for advisory board but has no relationship with this work., Grant/research support from: Have received a research grant from Pfizer; but has no relationship with this work., Ronald C. Eldridge: None declared, Glenna S. Brewster: None declared, Nicole S. Carlson: None declared, Elizabeth J. Corwin: None declared
Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates