Causal relationships between systemic inflammatory cytokines and adhesive capsulitis: a bidirectional Mendelian...

Area of Science:

• Immunology
• Genetics
• Rheumatology

Background:

• Adhesive capsulitis (AC) is linked to inflammatory cytokines, but specific causal factors remain unclear.
• Understanding these systemic inflammatory cytokines is crucial for AC pathogenesis.
• This study investigates 41 inflammatory cytokines and their causal relationship with AC.

Purpose of the Study:

• To identify specific systemic inflammatory cytokines causally associated with adhesive capsulitis (AC).
• To explore bidirectional causal relationships between inflammatory cytokines and AC using Mendelian randomization.

Main Methods:

• Bidirectional, two-sample Mendelian randomization (MR) analysis.
• Utilized genome-wide association study (GWAS) data for AC and 41 inflammatory cytokines.
• Employed inverse variance weighting (IVW) and sensitivity analyses (MR-Egger, weighted median).

Main Results:

• Elevated interferon gamma-induced protein 10 (IP-10) and RANTES associated with increased AC risk.
• Increased stromal cell-derived factor-1 alpha (SDF-1α) and tumor necrosis factor-alpha (TNF-α) linked to reduced AC risk.
• AC associated with increased CTACK and decreased IL-17 and IL-5 levels.

Conclusions:

• Establishes causal links between IP-10, RANTES, SDF-1α, TNF-α, and AC risk.
• AC influences CTACK, IL-17, and IL-5 levels, indicating a complex interplay.
• Findings advance understanding of AC pathogenesis and potential therapeutic targets.