Exploring expression levels of the cGAS-STING pathway genes in peripheral blood mononuclear cells of spinal tuberculosis patients

BMC Infect Dis. 2024 Sep 4;24(1):915. doi: 10.1186/s12879-024-09815-x.

Abstract

Background: This study aimed to investigate the differential expression levels of the cGAS-STING pathway in peripheral blood mononuclear cells (PBMCs) of spinal tuberculosis (TB) patients with different progression and its feasibility as a diagnostic marker.

Methods: Peripheral blood and medical records of 25 patients with spinal TB and 10 healthy individuals, were prospectively collected and analyzed. PBMCs and serum were extracted from peripheral blood and the expression levels of the cGAS-STING pathway in PBMCs were measured by real-time PCR (RT-PCR) and serum interferon β (IFN-β) expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of Interferon regulatory Factor 3 (IRF3) in PBMCs was measured using western blot. Statistical analysis was performed using the SPSS 26.0 statistical package.

Results: The results showed that the expression level of the TANK-binding kinase 1 (TBK1) and IRF3 was significantly higher in PBMCs (P < 0.05), in patients with active lesions than in patients with stable lesions. The serum concentration of IFN-β was significantly higher in patients with active lesions (P = 0.028). Compared with healthy individuals, the expression level of the cGAS-STING pathway was elevated in PBMCs of TB patients (P < 0.05), and the difference in the expression level of IFN-β was not statistically significant (P > 0.05), and the serum IFN-β concentration was elevated (P < 0.05). The calculated AUC values for TBK1 and IRF3 in PBMCs, IFN-β in serum and erythrocyte sedimentation rate (ESR) to distinguish between patients with active and stable lesions were 0.732, 0.714, 0.839, and 0.714 respectively.

Conclusions: The expression level of TBK1 and IRF3 in PBMCs, and IFN-β in the serum of patients with spinal TB is positively correlated with disease activity. TBK1 has higher specificity and IFN-β in serum has higher sensitivity when used to differentiate between patients with active and stable lesions.

Keywords: Activity; Diagnostic marker; PBMCs; Spinal tuberculosis; cGAS-STING.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Female
  • Humans
  • Interferon Regulatory Factor-3* / blood
  • Interferon Regulatory Factor-3* / genetics
  • Interferon Regulatory Factor-3* / metabolism
  • Interferon-beta / blood
  • Leukocytes, Mononuclear* / metabolism
  • Male
  • Membrane Proteins* / blood
  • Membrane Proteins* / genetics
  • Middle Aged
  • Nucleotidyltransferases* / genetics
  • Prospective Studies
  • Protein Serine-Threonine Kinases / genetics
  • Signal Transduction
  • Tuberculosis, Spinal* / blood
  • Tuberculosis, Spinal* / genetics
  • Young Adult

Substances

  • Membrane Proteins
  • Nucleotidyltransferases
  • cGAS protein, human
  • STING1 protein, human
  • Interferon Regulatory Factor-3
  • Interferon-beta
  • TBK1 protein, human
  • Protein Serine-Threonine Kinases
  • Biomarkers
  • IRF3 protein, human