Identification of immunodiagnostic blood biomarkers associated with spinal cord injury severity

Front Immunol. 2023 Mar 29:14:1101564. doi: 10.3389/fimmu.2023.1101564. eCollection 2023.

Abstract

Blood always shows some immune changes after spinal cord injury (SCI), and detection of such changes in blood may be helpful for diagnosis and treatment of SCI. However, studies to date on blood immune changes after SCI in humans are not comprehensive. Therefore, to obtain the characteristics of blood immune changes and immunodiagnostic blood biomarkers of SCI and its different grades, a human blood transcriptome sequencing dataset was downloaded and analyzed to obtain differentially expressed immune-related genes (DEIGs), related functions and signaling pathways related to SCI and its various grades. Characteristic biomarkers of SCI and its different grades were identified by using weighted gene coexpression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) logistic regression. Expression of biomarkers was verified through experiments. The area under the curve (AUC) of biomarkers was calculated to evaluate their diagnostic value, and differences in immune cell content were examined. In this study, 17 kinds of immune cells with different contents between the SCI group and healthy control (HC) group were identified, with 7 immune cell types being significantly increased. Differences in the content of immune cells between different grades of SCI and the HC group were also discovered. DEIGs were identified, with alteration in some immune-related signaling pathways, vascular endothelial growth factor signaling pathways, and axon guidance signaling pathways. The SCI biomarkers identified and those of American Spinal Injury Society Impairment Scale (AIS) A and AIS D of SCI have certain diagnostic sensitivity. Analysis of the correlation of immune cells and biomarkers showed that biomarkers of SCI, AIS A grade and AIS D grade correlated positively or negatively with some immune cells. CKLF, EDNRB, FCER1G, SORT1, and TNFSF13B can be used as immune biomarkers for SCI. Additionally, GDF11and HSPA1L can be used as biomarkers of SCI AIS A grade; PRKCA and CMTM2 can be used as biomarkers of the SCI AIS D grade. Detecting expression of these putative biomarkers and changes in related immune cells may be helpful for predicting the severity of SCI.

Keywords: biomarkers; blood; diagnosis; immune cells; immune-related genes; spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Humans
  • Spinal Cord Injuries* / diagnosis
  • Spinal Cord Injuries* / therapy
  • United States
  • Vascular Endothelial Growth Factor A*

Substances

  • Vascular Endothelial Growth Factor A
  • Biomarkers

Grants and funding

This study was supported by the National Natural Science Foundation of China (U22A20162, 31900583, 32071351, 81772400, 82102604, 81960395), the Natural Science Foundation of Guangzhou City (201807010031), foundation of Shenzhen Committee for Science and Technology Innovation (JCYJ20190809142211354, GJHZ20180929160004704), Sanming Project of Medicine in Shenzhen (SZSM201911002), the Beijing Municipal Health Commission (Grant No. BMHC-2021-6, BMHC-2019-9, BMHC-2018-4, PXM2020_026275_000002), AOCMF Translational approaches for bone constructs (AOCMF-21-04S), Sun Yat-sen University Clinical Research 5010 Program (2019009), Academic Affairs Office of Sun Yat-sen University (202211583, 202211589).