Comprehensive profiling of immune landscape changes and oxidative stress-associated biomarkers in intervertebral disc degeneration

Background Intervertebral disc degeneration (IDD) is often considered a cause of low back pain. Oxidative stress and the dysregulation of the immune microenvironment are well recognized as important players in this pathology. However, the global knowledge about the core genes that are related to the oxidative stress and how they are involved in the immune response is still missing. Methods We integrated transcriptomic data from three IDD cohorts (GSE167199, GSE176205, GSE186542) and performed differential expression analysis, WGCNA, consensus clustering, and CIBERSORT to identify oxidative stress-related genes, define molecular subtypes, and evaluate immune infiltration. We further constructed single-gene GSEA models, ceRNA networks, and TF-mRNA interactions. Biomarker validity was tested via qPCR and IHC in human samples, and immunofluorescence in a rat puncture model. Results The study revealed two novel IDD subtypes with distinct oxidative stress signatures, and identified CD36, SESN3, and HMOX1 as key regulators. Their expression correlated with immune infiltration, particularly resting mast cells, naïve CD4 + T cells, and macrophages. GSEA linked them to cell cycle, metabolism, and cytokine pathways, while ceRNA and TF networks revealed complex regulation involving lncRNAs, miRNAs, and transcription factors. Validation confirmed their upregulation in human and rat degenerated discs, highlighting their diagnostic and therapeutic potential. Conclusion The study used bioinformatics to identify and suggest CD36, SESN3 and HMOX1 as potential oxidative stress-associated biomarkers in IDD, and also underlines their strong relationship with the remodeling of the immune microenvironment. These results contribute to a better understanding of the relationship between oxidative processes and immune response in the context of the disc degeneration, and may help to conceive future therapeutic approaches with antioxidant and immunomodulatory effects.