The causal relationship between multiple autoimmune diseases and nasal polyps

Area of Science:

• Immunology
• Genetics
• Otolaryngology

Background:

• Previous studies on autoimmune diseases and nasal polyps had conflicting results, small sample sizes, and low evidence.
• The complex interplay between autoimmune conditions and sinonasal pathology requires further investigation.

Purpose of the Study:

• To investigate the causal relationships between nine autoimmune diseases and nasal polyps using Mendelian randomization.
• To explore potential sex-specific differences in these causal associations.
• To elucidate underlying mechanisms through mediation analyses.

Main Methods:

• Utilized bidirectional univariable and multivariable Mendelian randomization analyses.
• Employed rigorous instrumental variable screening.
• Conducted mediation analyses to explore causal pathways.

Main Results:

• A causal association was found between adult-onset Still's disease and nasal polyps.
• Rheumatoid arthritis showed a causal relationship with nasal polyps, partly mediated by BAFF-R for IgD+ B cells.
• Sex-specific associations were observed, with some autoimmune diseases showing stronger effects in males.

Conclusions:

• Established causal links between specific autoimmune diseases and nasal polyps.
• Identified sex bimodality in the causal effects, with stronger associations in males.
• Provides a foundation for early identification of individuals susceptible to nasal polyps and understanding disease immunopathogenesis.