Absolute quantification and characterization of oxylipins in lupus nephritis and systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multi-organ inflammation and defect, which is linked to many molecule mediators. Oxylipins as a class of lipid mediator have not been broadly investigated in SLE. Here, we applied targeted mass spectrometry analysis to screen the alteration of oxylipins in serum of 98 SLE patients and 106 healthy controls. The correlation of oxylipins to lupus nephritis (LN) and SLE disease activity, and the biomarkers for SLE classification, were analyzed. Among 128 oxylipins analyzed, 92 were absolutely quantified and 26 were significantly changed. They were mainly generated from the metabolism of several polyunsaturated fatty acids, including arachidonic acid (AA), linoleic acid (LA), docosahexanoic acid (DHA), eicosapentanoic acid (EPA) and dihomo-γ-linolenic acid (DGLA). Several oxylipins, especially those produced from AA, showed different abundance between patients with and without lupus nephritis (LN). The DGLA metabolic activity and DGLA generated PGE1, were significantly associated with SLE disease activity. Random forest-based machine learning identified a 5-oxylipin combination as potential biomarker for SLE classification with high accuracy. Seven individual oxylipin biomarkers were also identified with good performance in distinguishing SLE patients from healthy controls (individual AUC > 0.7). Interestingly, the biomarkers for differentiating SLE patients from healthy controls are distinct from the oxylipins differentially expressed in LN patients vs. non-LN patients. This study provides possibilities for the understanding of SLE characteristics and the development of new tools for SLE classification.

Exploring the causal correlations between 486 serum metabolites and systemic lupus erythematosus: a bidirectional Mendelian randomization study

“…In SLE, several oxylipins have been identified to be significantly changed and critical for SLE pathophysiology, suggesting the potential utility of oxylipins as candidate biomarkers for SLE diagnosis and clinical treatment (Hye Khan et al, 2019;He et al, 2020b). Jingquan H et al used targeted mass spectrometry analysis to explore the alteration of oxylipins in the serum of 98 SLE patients and 106 healthy controls (He et al, 2022). The negative correlation of linolenic acid with lupus nephritis and SLE disease activity is consistent with our study.…”

Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review

“…Notably, lupus nephritis (LN), a common and severe complication of SLE occurring in approximately 40% of SLE patients [ 283 ], can be differentiated from SLE based on distinct serum oxylipin profiles. These profiles include several polyunsaturated fatty acids, such as arachidonic acid, linoleic acid, docosahexaenoic acid, eicosapentaenoic acid, and dihomo- -linolenic acid [ 284 ]. Furthermore, glycerophospholipid metabolism changes have been associated with the progression of SLE to LN.…”

Systemic lupus in the era of machine learning medicine

“… 118 For non-renal SLE, FOXP3, 88 MX2, 106 HLA-DQA1, 90 HLA-DQB1, 90 HLA-DRB1, 90 neutrophil extracellular trap-related genes (HMGB1, ITGB2 and CREB5), 70 ABCB1, 120 IFI27 120 and PLSCR1 120 have been reported. Other types of biomarkers included proteomics (IFIT3, MX1, TOMM40, STAT1, STAT2 and OAS3), 101 metabolomics, 91 lipidomics 94 and microRNA profiles. 108 …”