Immune system expression profiling in patients experiencing low back pain: A pilot study

Background: Spine pathologies are associated with an inflammatory microenvironment, with previous studies demonstrating systemic inflammation based on analysis of serum from patients with low back pain (LBP). This pilot study used gene expression profiling to identify candidate cellular mechanisms mediating systemic inflammation in patients with LBP, with and without radicular pain, compared to asymptomatic controls. Objective: To identify differences in expression of inflammation- and immune-related genes in whole blood from patients with LBP and spine pathology compared to control participants. Also, identify relationships between differentially expressed (DE) genes and patient-reported outcomes (PROs) for pain (Visual Analog Scale [VAS]) and disability (Oswestry Disability Index [ODI]). Design: Case control, observational study. Setting: Outpatient clinic at academic institution. Patients: Nine participants with LBP who were 18 years or older and diagnosed with lumbar disc herniation, spinal stenosis, or disc degeneration. Eight control participants who were 18 years or older and had no history of LBP or spinal treatment. Interventions: N/A. Main outcome measure: Expression levels of inflammation- and immune-related genes in patients with LBP compared to control participants measured using Nanostring nCounter analysis. Results: Analysis of patients with LBP versus controls resulted in 11 DE genes (p-adj <.05) and 9 trending genes (p-adj <.1) falling into three clusters: “Interferon α/β Signaling,” “Immunoglobulin Binding,” and “Toll-like Receptor (TLR) Binding.” VAS scores were also associated with expression level of FCER1G, FCGR3A/B, and KLRK1. Further analysis showed significantly lower expression of FCER1G in patients with high versus low VAS (p <.05). No relationships between DE gene expression and ODI was identified; however, a significant correlation between VAS and ODI scores was observed (p <.05). Conclusions: Clustering of DE and trending genes suggested increased interferon α/β signaling and TLR signaling may contribute to systemic inflammation related to LBP. Immunoglobulin binding was also implicated and varied with pain severity in patients with LBP.