Whole Blood and Plasma-Based Lipid Profiling Reveals Distinctive Metabolic Changes in Systemic Lupus Erythematosus and Systemic Sclerosis

Autoimmune diseases (AID), such as systemic lupus erythematosus(SLE) and systemic sclerosis (SS), are complex conditions involvingimmune system dysregulation. Diagnosis is challenging, requiring biomarkersfor improved detection and prediction of relapses. Lipids have emergedas potential biomarkers due to their role in inflammation and immuneresponse. This study uses an untargeted C18 RP-LC-MS lipidomics approachto comprehensively assess changes in lipid profiles in patients withSLE and SS. By analyzing whole blood and plasma, the study aims tosimplify the lipidomic analysis, explore cellular-level lipids, andcompare lipid signatures of SLE and SS with healthy controls. Ourfindings showed variations in the lipid profile of SLE and SS. Sphingomyelinand ceramide molecular species showed significant increases in plasmasamples from SS patients, suggesting an atherosclerotic profile andpotentially serving as lipid biomarkers. Phosphatidylserine speciesin whole blood from SLE patients exhibited elevated levels supportingpreviously reported dysregulated processes of cell death and defectiveclearance of dying cells in this AID. Moreover, decreased phospholipidsbearing PUFA were observed, potentially attributed to the degradationof these species through lipid peroxidation processes. Further studiesare needed to better understand the role of lipids in the pathologicalmechanisms underlying SLE and SS.