Exploring causal correlations between inflammatory cytokines and ankylosing spondylitis: a bidirectional...

Area of Science:

• Genetics
• Immunology
• Rheumatology

Background:

• The role of inflammation in Ankylosing Spondylitis (AS) is known, but causal links are unclear.
• Investigating genetic associations between inflammatory factors and AS is crucial for understanding pathogenesis.

Purpose of the Study:

• To explore the potential causal relationships between inflammatory cytokines and the risk of developing Ankylosing Spondylitis (AS) using a bidirectional Mendelian-randomization approach.
• To identify inflammatory biomarkers that may be associated with AS risk or be affected by the condition.

Main Methods:

• A bidirectional Mendelian-randomization study was conducted using GWAS data from AS cases and controls, and summary statistics for inflammatory cytokines.
• Inverse variance-weighted method, MR Egger, weighted median, and weighted mode analyses were employed to assess causal associations.
• Cochrane Q test, MR-Egger intercept, MR-PRESSO, and leave-one-out analyses were used to evaluate heterogeneity, pleiotropy, and robustness.

Main Results:

• Genetic predisposition to elevated beta-nerve growth factor (βNGF), Interleukin-1-beta (IL-1β), and TNF-related apoptosis inducing ligand (TRAIL) showed potential associations with increased AS risk.
• AS was genetically predicted to influence the expression of numerous cytokines, including IL-12p70, IL-17, IL-6, IL-4, SDF-1α, MIP1β, MCP-3, PDGFbb, GCSF, bFGF, TRAIL, and IFN-γ.
• No significant heterogeneity or horizontal pleiotropy was detected, confirming the reliability of the findings.

Conclusions:

• βNGF, IL-1β, and TRAIL may be significant contributors to AS pathogenesis.
• AS may influence the expression levels of a wide range of cytokines, highlighting complex inflammatory interactions.
• Further research is needed to validate these findings and explore their potential as therapeutic or diagnostic targets for AS.