Association of local Igs with disease severity in patients with NCFB: data from the EMBARC-BRIDGE study

Ig substitution improves survival and decreases exacerbations in patients with immunodeficiency and NCFB. The extent to which local Igs from the respiratory tract are related to disease severity among immunocompetent patients is still unknown. Understanding the role of local immune defense in NCFB progression may contribute to the development of novel treatments. We aimed to investigate the association of local Igs with disease severity in immunocompetent patients with NCFB. We obtained clinical data and sputum from the cohort at baseline. Igs were quantified in sputum supernatants using ELISA. We defined three groups of severity according to the bronchiectasis severity score (BSI). We compared Igs concentrations using an ordered logistic regression with the severity group as the dependent variable and calculated the trend p-value for the ratio between the concentration of IgA/IgG across the spectrum of severity. We also compared the IgG fragmentation by severity. <bold>Results:</bold> We included 227 patients. The distribution of the samples according to the mild, moderate and severe groups, as determined by the BSI, was 26%, 47%, and 27%, respectively. We found a non-significant trend of increasing IgG and decreasing IgA concentrations from low to medium to high BSI. The ratio between the concentration of IgA/IgG showed an inverse association with the BSI (p-trend=0.002). A direct association was found across groups with respect to IgG fragmentation. Fragmented IgG varied from 29% in the low-risk group to 41% in the high-risk group (p=0.04). <bold>Conclusion:</bold> local Igs are associated with disease severity in NCFB. Increased IgG fragmentation may indicate less functional antimicrobial defences in the severe group.