Tu146 - Metabolomics Analysis Reveals Common and Differentiating Metabolic Phenotypes in Peripheral Blood Mononuclear Cells from Type 1 Diabetes, Systemic Lupus Erythematosus and Healthy Participants

Elmar Zügner, Dr. – Joanneum Research Forschungsgesellschaft m.b.H, Graz, Austria; Barbara Prietl, Dr. – Center for Biomarker Research in Medicine (CBmed), Graz, Austria; Martin Stradner, Dr. – Associate Professor, Division of Rheumatology and Clinical Immunology, Medical University of Graz; Stefanie Stanzer, Dr. – Center for Biomarker Research in Medicine (CBmed), Graz, Austria; Joakim Franz, MSc – Center for Biomarker Research in Medicine (CBmed), Graz, Austria; Karin Mattersdorfer, MSc – Center for Biomarker Research in Medicine (CBmed), Graz, Austria; Denise Schimek, MSc – Joanneum Research Forschungsgesellschaft m.b.H, Graz, Austria; Eva-Maria Prugger, MSc – Joanneum Research Forschungsgesellschaft m.b.H, Graz, Austria; Christoph Magnes, Dr. – Joanneum Research Forschungsgesellschaft m.b.H, Graz, Austria; Harald Sourij, Dr. – Associate Professor, Division of Endocrinology and Diabetology, Medical University of Graz; Thomas Pieber, Dr. – Professor, Division of Endocrinology and Diabetology, Medical University of Graz

Abstract Text: Identifying the metabolic reprogramming associated with autoimmune diseases can generate novel insights of disease mechanism. We compared the intracellular metabolic profile and the metabolic responses to immune activation in peripheral blood mononuclear cells (PBMCs) from type 1 diabetes patients (T1D, n = 24), systemic lupus erythematosus patients (SLE, n = 22) and healthy controls (n = 26). PBMCs from each participant were subjected to T-cell stimulation by anti-CD3/CD28 dynabeads® or placebo for 24h. The intracellular metabolites were measured using UHPLC-MS metabolomics. Data was analyzed using a mixed effect model with stimulation, health group and stimulation × health group as fixed factors and participant as a random factor. Bonferroni correction was performed to account for multiple testing.
Stimulation of PBMCs led to significant increase in intracellular lysophosphatidylethanolamine C16:0, phosphocholine, citric acid, hexose diphosphate, taurine, and uridine. Phenylacetic acid was higher (health group effect p-value = 0.003) and hippuric acid (p-value = 0.005) was lower in T1D and SLE compared with healthy, albeit not after Bonferroni correction. Isorhamnetin was reduced in T1D and SLE in response to stimulation compared with healthy participant (stimulation × health effect p-value = 0.003).
Our findings show shifts in lipid and energy metabolism in PBMCs after stimulation regardless of the health status. Phenylacetic acid, hippuric acid and isorhamnetin, which represent a differentiating metabolism in T1D and SLE than healthy, are the intermediates in the metabolism of phenolic compounds and their changes suggest a shift in xenobiotic metabolism. Therefore, xenobiotic metabolism under autoimmune diseases warrants further investigations.