Peripheral immunosuppressive and immunostimulatory signatures of severity and pain in spinal cord injury

Spinal cord injury is a severe neurological condition associated with an increased risk of infection, an elevated mortality rate, and often results in chronic neuropathic pain. The peripheral immune changes in the chronic phase of spinal cord injury are largely unknown, as is their capacity to facilitate neuropathic pain. The current study used a high-dimensional single-cell analysis of peripheral blood to evaluate major immune populations and functional markers in individuals with chronic spinal injury. Spinal cord injury was associated with a shift towards classical monocytes and an increase in granulocytic myeloid-derived suppressor cells. There were also reductions in NK cells and B cells, as well as impairments to memory T cell functioning. The elevation of classical monocytes and decrease in NK cells were more pronounced in injured individuals with neuropathic pain, a high spinal level of lesion, and a moderate, but not severe injury. These findings highlight the cell-specific systemic immune dysfunction in chronic spinal cord injury and how more severe clinical subgroups are largely associated with greater immune impairment. Therefore, targeting immune dysfunction may lead to an improvement in symptom severity, whilst biomarkers of immune dysfunction may be useful in predicting the clinical trajectory.