The causal relationship between immune cells and ankylosing spondylitis: a bidirectional Mendelian randomization...

Area of Science:

• Immunogenetics
• Rheumatology
• Epidemiology

Background:

• Ankylosing spondylitis (AS) is a type of seronegative spinal arthritis with unknown etiology.
• Inflammatory and immunological factors are implicated in AS development, but previous research yielded inconclusive results.
• Understanding the immunological underpinnings of AS is crucial for advancing treatment and prevention strategies.

Purpose of the Study:

• To evaluate the causal association between immunological characteristics and the risk of developing ankylosing spondylitis (AS).
• To investigate the bidirectional relationship between 731 immune cell features and AS using genetic data.
• To identify specific immune cell types that may play a causal role in AS pathogenesis.

Main Methods:

• A bidirectional, two-sample Mendelian randomization (MR) approach was employed.
• Utilized large-scale, publicly available genome-wide association study (GWAS) datasets.
• Analyzed the causal connection between 731 immunological feature characteristic cells and AS risk.

Main Results:

• Two immunophenotypes, CD14-CD16+ monocyte and CD33dim HLA DR+CD11b+, were significantly associated with reduced AS risk (P < 0.05 FDR corrected).
• Ankylosing spondylitis (AS) showed statistically significant effects on six immune traits, including CD8+ T cells, IgD+ B cells, and natural killer T cells.
• Specific associations included decreased risk with CD14-CD16+ monocytes and CD33dim HLA DR+CD11b+ cells, and altered levels of CD8+ T cells and B cell subsets in AS patients.

Conclusions:

• The study establishes a genetic link between specific immune cell populations and ankylosing spondylitis (AS).
• These findings provide novel insights into the immunological basis of AS.
• Results can inform future clinical and basic research directions for AS.