Blood immune profiles in chronic low back pain patients with type 1 Modic changes are associated with intradiscal propionic acid levels.

BACKGROUND: Modic type 1 changes (MC1) are vertebral endplate bone marrow lesions associated with chronic low back pain (CLBP), but their underlying pathobiology remains unclear. Disc-bone marrow crosstalk that includes Cutibacterium acnes (C. acnes) infection of the disc and immune system activation in the adjacent vertebrae may be a defining feature of some MC1. METHODS: In a prospective analysis of patients from the UCSF comeBACK cohort, we quantified intradiscal propionic acid (PA) - a metabolic product of C. acnes - using magnetic resonance spectroscopy (MRS). Patients were stratified into tertiles based on intradiscal PA content, and the uppermost (PA-high) and lowermost (PA-low) tertiles were compared for systemic immune signatures, including whole-blood transcriptomics (n = 196), flow cytometry immunophenotyping (n = 224), and serum cytokine profiling (n = 398). RESULTS: High intradiscal PA was associated with distinct systemic immune responses in patients with MC1 but not in patients with Modic type 2 changes or without Modic changes. Transcriptomic analysis revealed enrichment of adaptive immune pathways and B cell activation signatures in PA-high MC1. Flow cytometry identified the expansion of immunosuppressive ectonucleotidases CD39 and CD73-expressing B cells in PA-high MC1 patients. Finally, intradiscal PA levels were correlated with circulating B cells and serum cytokine concentrations. CONCLUSIONS: Intradiscal PA levels measured by MRS associate with biologically distinct blood profiles characterised by systemic B cell activation in patients with MC1. These findings suggest a systemic immune component in the pathobiology of MC1 and highlight the potential of MRS-derived intradiscal PA levels to stratify patients with MC1-related chronic low back pain into biologically distinct subgroups.