Multi-Omics Analysis Defines Endotypes and Systemic Inflammation in Primary Ciliary Dyskinesia: A Comparison with...

Area of Science:

• Genetics and Immunology
• Rare Diseases
• Respiratory Medicine

Background:

• Primary ciliary dyskinesia (PCD) is a rare genetic disorder causing chronic airway inflammation and lung damage.
• The precise inflammatory profile and systemic involvement in PCD are not well understood.
• Investigating non-invasive markers for systemic inflammation is crucial for disease management.

Purpose of the Study:

• To characterize inflammatory signatures in PCD using multi-omics approaches.
• To evaluate saliva as a non-invasive biomarker for systemic inflammation in PCD.
• To identify distinct inflammatory endotypes within the PCD population.

Main Methods:

• Cross-sectional, multicenter study comparing PCD patients and healthy controls.
• Integrated multi-omics analysis: transcriptomics, proteomics (saliva and plasma), and metagenomics.
• NanoString nCounter® for gene expression, NULISA™ for protein profiling, and metagenomic sequencing for microbiome analysis.

Main Results:

• PCD patients exhibited elevated inflammatory gene and protein expression in saliva and plasma, particularly older individuals and those with microtubular defects.
• Five inflammatory endotypes were identified, with neutrophilic pathways (DPP-1, Th17) being most common, alongside a Th2-predominant subset.
• Strong molecular concordance was observed between saliva and plasma inflammatory profiles; microbiome shifts correlated with inflammation.

Conclusions:

• PCD is characterized by significant baseline inflammation with notable endotypic heterogeneity, often involving neutrophilic pathways.
• Salivary inflammatory profiling provides a practical, non-invasive method to assess systemic inflammation and patient heterogeneity in PCD.
• This approach can aid in monitoring disease activity and treatment response, especially with emerging therapies for bronchiectasis.