Immunometabolism in rheumatoid arthritis: mechanisms, biomarkers, and the path to precision medicine

TL;DR

This paper explores how immune cell metabolism contributes to rheumatoid arthritis and how this knowledge can lead to better personalized treatments.

Contribution

The paper introduces a new framework for integrating immunometabolic profiling into precision medicine for rheumatoid arthritis.

Findings

Immunometabolic dysregulation in immune and stromal cells drives rheumatoid arthritis pathology.

High-dimensional biomarkers can help predict treatment responses in rheumatoid arthritis patients.

Targeting immunometabolic pathways with drugs like metformin shows promise for personalized treatment.

Abstract

Synovitis and gradual joint degeneration are hallmarks of rheumatoid arthritis (RA), a chronic inflammatory illness. To sustain inflammation and tissue damage, pathogenic immune and stromal cells undergo specific metabolic reprogramming that alters glycolysis, oxidative phosphorylation, and lipid metabolism. This pathology is driven by immunometabolic dysregulation, according to new research. This review summarizes the current understanding of cell-type-specific immunometabolic dysregulation in RA, with particular attention to T cells, macrophages, B cells, and fibroblast-like synoviocytes. We assess how high-dimensional biomarkers, such as blood-based metabolomic, transcriptomic, and proteomic signatures, and synovial molecular pathotypes can be used to stratify patients and predict how well biologic and targeted treatments will work. We also reviewed treatment approaches targeting immunometabolic pathways, including new metabolic inhibitors and drug repurposing, such as metformin. To facilitate a more individualized and efficient RA treatment, we conclude by offering a clinically applicable paradigm to integrate immunometabolic profiling into precision medicine.

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