A protein associated with pregnancy is linked to disease severity and frequent exacerbations in people with bronchiectasis and chronic chest infections (that are mostly caused by Pseudomonas aeruginosa), a study suggests.
Bacteria could be “hijacking” a body’s natural process to shield themselves from the immune system, and persist in the airways, according to researchers at the University of Dundee. Therefore, approaches that boost the immune system could be successful against chronic respiratory infections, the team said.
The data were presented at the recent European Respiratory Society (ERS) 2019 International Congress, in Madrid, and described in the study “the American Journal of Respiratory and Critical Care Medicine.
Pregnancy zone protein (PZP) is a powerful inhibitor of the immune system. It is produced by men and women but its blood levels are higher during pregnancy, when it is believed to suppress the immune system to protect the fetus from being rejected.
Although work in mice suggested that PZP increases susceptibility to viral infections, the protein has not been reported in the airways or studied in chronic respiratory disease.
“People with chronic lung diseases are far more likely to get regular chest infections. Despite this fact, we find that the body’s normal mechanisms for dealing with infection doesn’t work properly in those situations, which leaves patients trapped in a vicious cycle of coughing and spluttering from frequent chest infections,” James Chalmers, PhD, professor at the University of Dundee and lead author of the study, said in a university news release, written by Grant Hill.
To investigate whether PZP could be associated with airway infections in bronchiectasis and other lung diseases, the researchers took samples from 124 people with bronchiectasis and 40 patients with chronic obstructive pulmonary disease (COPD), and analyzed the concentrations of PZP in their sputum (coughed-up mucus) and blood.
They found that PZP was present in sputum samples from people with COPD or bronchiectasis and those with chest infections, but not in healthy people.
Also, higher levels of PZP in the sputum were correlated with bacterial infections, mainly caused by P. aeruginosa.
Higher sputum PZP levels also correlated with greater disease severity, more frequent infections, reduced lung function, and quality of life — as assessed by the Quality of Life Bronchiectasis Respiratory Symptom Score — and with a higher amount of bacteria in the airways.
Consistent with these observations, treatment with antibiotics reduced PZP production in the airways of patients with bronchiectasis and chest infections.
A more detailed analysis revealed that a type of white blood cell, called neutrophils, was responsible for the release of PZP in the airways of patients.
In response to infections and other triggers, neutrophils launch a defense system called neutrophil extracellular traps (NETs), which can immobilize invading microorganisms. In vitro experiments showed that neutrophils also release high concentrations of PZP, and confirmed the presence of this protein within NETs.
“We report a novel link between airway infection, NET formation, and disease severity in bronchiectasis during chronic airway inflammation,” the researchers wrote.
“We were surprised to find PZP in the lungs, but this might explain why people with chronic lung disease cannot clear these infections easily. We believe that the bacteria are ‘hijacking’ the body’s natural processes during pregnancy, activating the production of PZP, and shielding themselves from the immune system,” Chalmers said.
“These findings present a new opportunity to treat those people with the most severe types of chest infection, by kickstarting the body’s natural defense mechanisms, and helping break the vicious cycle of chest infections,” he added.