Peripheral SBK1 and ADGRG5 as Biomarkers of Cell Adhesion Molecule-Associated Immune Alterations after Spinal Cord Injury

Abstract

Immune dysregulation is a central component of secondary injury processes following spinal cord injury (SCI). Cell adhesion molecules (CAMs) play key roles in leukocyte-endothelium interactions and neuroimmune communication after neurotrauma; however, their potential as clinically accessible peripheral blood biomarkers reflecting immune alterations after SCI remains insufficiently defined. Transcriptomic datasets derived from peripheral blood of individuals with SCI and healthy controls (GSE151371 and GSE226238) were analyzed to identify CAM-related genes associated with post-injury immune dysregulation. Integrated differential expression analysis, weighted gene co-expression network analysis, and least absolute shrinkage and selection operator regression were applied for feature selection. Discriminative performance was evaluated using receiver operating characteristic analysis. Functional enrichment and immune cell deconvolution analyses were conducted to characterize immune associations. Key findings were validated in an independent transcriptomic cohort and further confirmed by quantitative RT-PCR using serum samples from individuals with SCI. Integrative bioinformatics analyses identified 99 CAM-associated candidate genes, which were further refined to six feature genes. Among these, SBK1, ADGRG5, and TCF7 were consistently downregulated in SCI across independent datasets. SBK1 and ADGRG5 demonstrated good discriminative performance, with area under the curve values of 0.85 and 0.83, respectively. Immune deconvolution revealed significant alterations in peripheral immune cell composition, including resting natural killer (NK) cells and naïve CD4⁺ T cells. Expression levels of SBK1 and ADGRG5 positively correlated with these immune cell populations. Serum-based RT-quantitative real-time PCR validation confirmed significant downregulation of SBK1 and ADGRG5 in SCI individuals compared with healthy controls. SBK1 and ADGRG5 were identified as CAM-related genes that were downregulated in peripheral blood after SCI and associated with distinct alterations in peripheral immune cell profiles, particularly involving CD4⁺ T cells and resting NK cells. These findings suggest that SBK1 and ADGRG5 may serve as accessible peripheral transcriptional biomarkers associated with post-SCI neuro-immune dysregulation and may support immune monitoring and patient stratification following SCI.