DBI Mediates the Progression of Ankylosing Spondylitis by Regulating CD56dim NK Cells Cytotoxicity Function.

BACKGROUND

Ankylosing spondylitis (AS) is an autoimmune disease characterized by low back stiffness and pain, with no cure and a dearth of therapeutic targets.

METHODS

Identifying novel AS targets from a list of 5884 druggable genes using weighted gene coexpression network analysis (WGCNA), machine learning, and Mendelian randomization analysis. Investigating the biological functions of the targets through comprehensive bio-functional analyses; exploring immune-related functions of the targets based on single-cell analyses; developing a reliable AS risk prediction model based on the identified targets and clinical data; conducting target drug prediction and molecular docking based on the Enrichr database and the LeDock software.

RESULTS

A novel AS target, diazepam binding inhibitor (DBI), was identified from among 5884 druggable genes. Bio-functional enrichment analysis indicated that this gene plays a key role in AS by modulating lipid metabolism disorders. Furthermore, single-cell analysis revealed that the gene likely influences the onset or progression of AS by impairing the cytotoxic function of CD56dim natural killer (NK) cells. Finally, a reliable AS risk prediction model was developed using DBI and clinical data, and several potential therapeutic compounds were identified.

CONCLUSION

In this study, a novel therapeutic target for AS was identified using multiple algorithms, and it was found to be involved in lipid metabolism and cytotoxic function of CD56dim NK cells. Additionally, a reliable prediction model was developed, and potential therapeutic compounds were identified. In conclusion, this study presents a novel approach for AS treatment.