ABSTRACT: Individuals with SCI are severely affected by immune system changes, resulting in a SCI-induced immune deficiency syndrome (SCI-IDS). While recent data support that acute SCI-IDS symptoms differ from those present in the chronic phase, only limited data in humans is available. To characterize dynamic molecular and cellular immune phenotypes over the first year, we assess RNA (bulk-RNA sequencing), protein, and flow cytometry (FACS) profiles of blood samples from 12 individuals with SCI at 0-3 days and at 3, 6, and 12 months post injury (MPI) compared to 23 uninjured individuals (controls). We identified 967 differentially expressed (DE) genes in individuals with SCI (FDR<0.001) compared to controls. Within the first 6 MPI we detected a reduced expression of NK cell genes, consistent with reduced frequencies of CD56bright, CD56dim NK cells present at 12 MPI. Over 6MPI, we observed increased and prolonged expression of genes associated with inflammation (e.g. HMGB1, Toll-like receptor signaling) and expanded frequencies of monocytes acutely. Canonical T-cell related DE genes (e.g. FOXP3, TCF7, CD4) were upregulated during the first 6 MPI and increased frequencies of activated T cells at 3-12 MPI were observed. Neurological injury severity was reflected in distinct whole blood gene expression profiles at any time after SCI, indicating a persistent ‘neurogenic’ imprint. Overall, 2876 DE genes emerge when comparing profiles of motor complete to motor incomplete SCI (ANOVA, FDR<0.05), including genes related to neutrophils, inflammation, and infection. In summary, we identify dynamic SCI-IDS determinants in humans, including molecular and cellular profiles, which may provide potential targets to reduce inflammation, improve immunity, or serve as candidate biomarkers of injury severity.
