Background and Aims

Common Variable Immunodeficiency (CVID) can lead to structural airway disease (AD), interstitial lung disease (ILD), and immune dysregulation in other organs. A role for microbial dysbiosis in the respiratory tract has been hypothesised, but not been investigated.

Methods

This cross-sectional study compared the oropharyngeal microbiota of 99 patients with CVID and 49 healthy controls. qPCR was used to determine total bacterial load. Next-generation sequencing of 16S rRNA was used to characterise microbiota composition. High-resolution CT (HRCT) scans were scored for AD and ILD and correlated with microbiota composition.

Results

Bacterial load was increased in CVID patients with immune dysregulation (CVIDid) (see figure; p=0.005; median fold change=16). IgA deficiency was associated with higher alpha diversity (p=0.008), and distinct beta diversity (p=0.019). Enrichment of Alloprevotella and Prevotella was associated with CVIDid (p=0.009;p=0.027) and IgA deficiency (p=0.002;p=0.003). Radiographic AD scores were associated with increased alpha diversity (p=0.037) and correlated with Prevotella (p=0.008), Moraxella (p=0.009) and Selenomonas (p=0.01) using linear regression. Radiographic ILD scores correlated with Actinobacteria (p=0.223) and Streptococcus pneumoniae (p=0.005).

Figure: Bacterial load- and 16S copy number-corrected 16S rRNA sequencing results. HC=healthy controls, CVIDio=CVID with infection only, CVIDid=CVID with immune dysregulation. MW-U test on total bacterial load per sample.

Conclusions

IgA-associated microbial dysbiosis in the upper respiratory tract, with increased bacterial load and diversity, correlated with radiographic lung disease In CVID patients. Prevotella spp were identified here as immune dysregulation-associated bacteria. This is the first study describing respiratory microbiota in humoral immunodeficiency, and illustrates the importance of IgA in the maintenance of respiratory microbiota homeostasis.