Antiglycation approach in selected autoimmune diseases: Where do we stand?

Advanced glycation end products (AGEs) and their receptor for advanced glycation end products (RAGE) have emerged as potential contributors to autoimmune pathology by linking metabolic stress, oxidative injury, and chronic inflammation. This review summarizes current mechanistic, preclinical, and clinical evidence on the role of the AGE-RAGE axis in selected autoimmune diseases, with a focus on systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, psoriasis, and multiple sclerosis. Across these conditions, increased AGE accumulation, enhanced availability of RAGE ligands, and altered soluble RAGE buffering appear to be recurring features associated with disease activity, organ damage, vascular complications, and immune dysregulation. Mechanistically, AGE-RAGE signaling amplifies nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and reactive oxygen species (ROS)-dependent pathways, promotes pro-inflammatory immune phenotypes, and may contribute to neoepitope generation and epitope spreading. We also discuss anti-glycation strategies, including carbonyl scavengers, AGE formation inhibitors, redox-modulating agents, crosslink breakers, and RAGE-targeting interventions. Although several compounds show promising anti-inflammatory and antiglycation effects in experimental models, autoimmune-specific translational evidence remains limited, and most studies do not include validated AGE/RAGE biomarkers. Overall, the AGE-RAGE axis represents a plausible therapeutic target in autoimmunity, but establishing its therapeutic potential will require standardized biomarker panels and well-designed clinical trials.