PCD is a motile ciliopathy associated with persistent airways infections, chronic inflammation and bronchiectasis. Besides a characteristic lack of mucociliary clearance, other intrinsic factors contributing to infection susceptibility are understudied.

We investigated differential protein expression to determine dysregulated biological processes in PCD nasal epithelia.

Primary human nasal epithelia from PCD (n=6; static cilia, class 1a transmission electron microscopy defects) and healthy (n=3) donors were ALI-cultured for 4-6 weeks (widespread ciliation by tubulin labelling). Mass spectrometry (MS) proteomics quantified relative protein expression between PCD and healthy donors. Differentially quantified proteins were used to determine biological processes by Gene Ontology Protein ANalysis Through Evolutionary Relationships.

We identified 151 significant differentially expressed proteins, 98 were up- and 53 down-regulated in PCD, compared with healthy epithelia. Notably, S100 proteins (cytoskeletal organisation) were enriched in PCD, whilst MUC5B (innate immunity critical) and HSP90 (downstream microbicidal activity) were diminished. Dysregulated biological processes were evident including increased oxidative stress, metabolic state, cell death, protein S-nitrosylation and actin-related cytoskeletal dysfunction.

Our combination of ALI-culture with MS proteomics captured aberrant cellular functionality in PCD nasal epithelia. Compared with healthy donors, we found differentially expressed proteins indicative of metabolic depletion, cellular damage and structural instability. Findings may explain the diminished capacity of PCD nasal epithelia to respond to microbial challenge.