Gamma delta T cells are expanded in the blood of chronic low back pain patients with lumbar Modic changes

Objectives Modic changes (MC) are vertebral endplate and bone marrow lesions strongly associated with chronic low back pain. Type 1 MC (MC1, oedema-like) and type 2 or 3 MC (MC2or3, fat- and sclerosis-like) are commonly regarded as different stages of the same pathological process, yet their underlying biology remains poorly defined. In particular, it remains unclear whether MC are confined to the spine or accompanied by distinct systemic immune alterations. Here, we provide the first comprehensive characterisation of the circulating immune landscape in patients with lumbar MC. Methods Peripheral blood mononuclear cells were analysed from 37 patients undergoing lumbar spinal surgery: 11 with no MC, 15 with MC1 and 11 with MC2or3. Samples were fluorescently barcoded, pooled, and stained with a 28-antibody phenotyping panel. Each pool was then split into 30 aliquots, and each of these was co-stained with a different PE-conjugated anti-integrin, -selectin, or -chemokine receptor antibody or isotype controls. Differences in abundance were tested with binomial mixed models adjusted for acquisition batch, age, and sex. Differentially abundant compartments were clustered by FlowSOM and the same binomial model was used to test differences in cluster abundance. Adhesion receptors were analysed as single chains. Results The γδ T cell compartment was the only population significantly expanded in MC patients (median 0.58% of all recorded cells in nonMC donors versus 1.61% in pooled MC (OR = 2.38, q = 0.035)). Clustering γδ T cells into subsets showed compartment-wide expansion, primarily driven by Vδ2+ T cells. The adhesion receptor screen revealed α6 and α2 integrin on basophils, endoglin on plasmacytoid dendritic cells, and β7 integrin on IgA⁺ B cells as differentially expressed in MC, but none survived multiple-testing correction across the whole screen. Conclusions Lumbar MC are accompanied by expansion of circulating γδ T cells. This aligns with previously reported γδ T cell accumulation in MC1 lesions, underscoring the role of γδ T cells in MC pathophysiology.