Introduction & Objective: Metabolic reprogramming has a critical role in the differentiation and function of PBMCs in autoimmune diseases. Here, comparative cellular immune-metabolomics was applied to multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and T1D.
Methods: PBMCs were isolated from healthy individuals (CTRLs, n=10), patients with T1D (n=11), MS (n=8), RA (n=14) and SLE (n=10). Obtained PBMCs were either T cell-stimulated using anti-CD3/CD28 dynabeads or treated with placebo. LC-HRMS metabolomics data was controlled for extraneous variables, submitted to statistical examination and pathway enrichment analysis.
Results: T1D shows a distinct dissimilarity to all tested autoimmune diseases and a striking congruence with controls (Fig.). MS, RA and SLE displayed enhanced metabolism concerning cell growth and death, energetics, transport and catabolism, and signal transduction, while these pathways were only moderately downregulated or not significantly altered in T1D. Metabolome after T cell activation shows a similar but less pronounced pattern.
Conclusion: T1D immune cell metabolome is closely related to that of healthy controls, whereas in MS, RA and SLE several metabolic pathways are highly deregulated. Our findings challenge the concept of immune interventions as monotherapies in T1D.
F. Monedeiro: None. E. Zügner: None. B. Prietl: None. M. Oberhuber: None. M. Stradner: Research Support; Novartis AG. Consultant; Janssen Pharmaceuticals, Inc. Speaker's Bureau; Pfizer Inc., AstraZeneca, Sobi, Eli Lilly and Company, Otsuka America Pharmaceutical, Inc., Bristol-Myers Squibb Company, Takeda Pharmaceutical Company Limited. M. Khalil: None. C. Magnes: None. T. Pieber: Advisory Panel; Arecor. Research Support; AstraZeneca. Consultant; Novo Nordisk A/S. Research Support; Novo Nordisk Foundation. Consultant; Lilly Diabetes, Sanofi. Speaker's Bureau; Roche Diabetes Care, Novo Nordisk.
COMET ? Common Mechanism in Autoimmunity, funded by JDRF and LRA (2-SRA-2021-1043-S-B).
