Upper airway immune dysfunction in otitis media with effusion (OME)

ABSTRACT NUMBER: FEGGETTER MEDAL FOR SENIOR TRAINEES (ST3+)_1

MAIN ABSTRACT TEXT

Introduction
Otitis media with effusion (OME; ‘glue ear’) is the most common cause of reversible hearing loss in developed countries. In the UK every year 24,000 children undergo surgery (grommets +/- adenoidectomy) for OME. Despite this, the mechanism by which adenoidectomy improves the resolution of OME remains unknown. Understanding this would aid the development of a ‘medical adenoidectomy’ – mitigating surgical risk in young children.

Methods
Paediatric patients (aged 2-6 years) undergoing adenoidectomy with and without OME were recruited (n=10). Adenoid biopsies were processed for single cell RNA sequencing and surface proteomics. 44,622 cells and 20,634 genes were analysed based on transcriptional signatures using bioinformatic pipelines (Scanpy, Dandelion, Milo) and compared between the OME vs non-OME cohorts.

Results
Adenoid tissue consists of 19 unique cell types; primarily composed of various forms of B and T cells – critical mediators of adaptive immunity. Innate immune cells were also identified, including: natural killer, dendritic, and innate lymphoid cells. Children in the OME cohort exhibited reduced IgA secretion and impaired memory T cell formation. Further, we identify a previously unknown cell type akin to Follicular Dendritic Cells (which functionally assist in antibody production) but which lack characteristic cytokine secretion, suggesting an alternative means of modulating antibody production.

Conclusion
We have comprehensively profiled adenoid tissue in health and disease. Children with OME exhibit a characteristic mucosal immunodeficiency in both innate and adaptive immune pathways. We have unexpectedly identified a previously unknown cell type with apparent importance in antibody production. This has importance in future intranasal vaccine strategies in children.