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.