Acute Immunological Phenotypes in Individuals with Traumatic Spinal Cord Injury.

Abstract

Acutely after traumatic spinal cord injury (SCI), the immune system responds with an inflammatory cascade that promotes secondary damage to the spinal cord and systemic inflammation, which promotes persistent medical consequences. Here, we combined clinical and research data to evaluate cellular and molecular changes in the systemic immune system of individuals with SCI (SCI, N = 36) within 0-4 days after injury compared to uninjured individuals (CTL, N = 36). Analyzing blood samples by bulk-RNA Seq, 4752 differentially expressed (DE) gene transcripts were identified in SCI compared with CTLs, including increased expression of genes associated with inflammation and innate immunity (e.g., Neutrophil degranulation, Toll-Like Receptor signaling). Most participants with SCI had complete blood count data available, of whom 36% had elevated white blood cell and neutrophil counts, 24% had elevated monocytes, and 36% had lymphopenia. Significantly reduced expression of canonical natural killer (NK) cell, T cell and dendritic cell (DC) genes were identified, consistent with reduced frequencies of these cell types, determined by flow cytometry. Some molecular changes appeared to be influenced by motor completeness of injury. C-reactive protein, a validated clinical biomarker of inflammation, was significantly elevated after SCI, with levels higher in motor complete compared to motor incomplete injuries. This was also apparent for several other proinflammatory cytokines (e.g., High Mobility Group Box 1 protein, IL-6, IL-8). These data confirm and extend prior observations of cellular and molecular immunological changes, that may serve as potential biomarkers of injury severity, or as future therapeutic targets to improve health.