Intradiscal propionic acid levels in chronic low back pain patients with Modic type 1 changes are associated with systemic immune cell activation

BackgroundModic type 1 changes (MC1) are vertebral endplate bone marrow lesions strongly associated with chronic low back pain (CLBP), but their underlying pathobiology remains unclear. Recent findings suggest that disc-bone marrow crosstalk that includes Cutibacterium acnes (C. acnes) infection of the disc, and immune system activation in the adjacent vertebrae may play a significant role. MethodsIn 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 lowest (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). ResultsElevated intradiscal PA was associated with distinct systemic immune responses in patients with MC1 but not in patients with Modic type 2 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-expressing B cells in PA-high MC1 patients. Finally, the correlation profiles of intradiscal PA levels and circulating B cells with serum cytokine concentrations were highly similar. Together, these data consistently indicate that systemic B cell activation is a hallmark of PA-high MC1. ConclusionIntradiscal PA, measurable non-invasively by MRS, stratifies MC1 patients into biologically distinct subgroups characterised by systemic B cell activation. These findings suggest a systemic immune component to MC1 pathobiology and highlight B cells as candidate biomarkers and therapeutic targets for MC1-related chronic low back pain.