Abstract

Introduction: Pregnancy zone protein (PZP) is a broad spectrum immunosuppressive protein originally discovered in the serum during pregnancy.  We identified PZP in the sputum of patients with Bronchiectasis using proteomics. In this study we aimed to characterise PZP in the bronchiectasis airway including its relationship with disease severity.

Methods: Patients were recruited from a specialist bronchiectasis clinic. PZP was measured in sputum and serum using ELISA. Neutrophils were imaged using immunoflouresence and electron microscopy.

Results: Median serum levels of PZP were 4.1 µg/ml (IQR 2.2-9.9), consistent with levels expected in healthy men and women. The median sputum level was more than tenfold higher at 65.9 µg/ml (IQR 36.9-205.8). There was no significant difference in sputum PZP between male and female patients.

Using the Bronchiectasis severity index we observed a relationship between sputum PZP and bronchiectasis severity. There was a significant elevated median sputum PZP in patients with severe disease (163 µg/ml (IQR 64.61-854.1)) compared to  mild (58.58µg/ml (IQR 25.29-163.8), or moderate  disease (52.64 (IQR 24.09-97.34),  (p<0.001). Patients with P. aeruginosa and those with worse quality of life also had higher sputum PZP.

PZP was released from peripheral blood neutrophils stimulated with PMA, fMLP and bacteria in a dose dependent manner. Imaging of neutrophils demonstrated that PZP is present in the cytoplasm of neutrophils and also associated with neutrophil extracellular traps (NETs).

Conclusion: Our results demonstrate for the first time that PZP is released from neutrophils during degranulation and NET formation and is associated with severity of bronchiectasis.