Antibody Evident in Airways of CF Patients Tied to P. aeruginosa Colonization

Antibody Evident in Airways of CF Patients Tied to P. aeruginosa Colonization
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The airways of cystic fibrosis (CF) patients show unusual levels of an antibody called BPI-ANCA, and they correlate with the amount of Pseudomonas aeruginosa bacteria found in their sputum, according to a recent study.

Evidence of both these antibodies and this bacteria in the airways may suggest a “vicious cycle” of inflammation and mucosal immunity, or immune responses at mucosal membranes, its researchers wrote.

Their study, “BPI-ANCA is expressed in the airways of cystic fibrosis patients and correlates to platelet numbers and Pseudomonas aeruginosa colonization,” was published in the journal Respiratory Medicine.

High blood levels of the BPI-ANCA antibody is also linked to poorer outcomes in patients, but less is known about those of the airways and how they relate to disease progression.

Little is also known about the presence of platelets — cells important for coagulation, inflammation and innate immunity — and of platelet-neutrophil complexes at sites of bacterial colonization.

Researchers with Lund University, in Sweden, sampled the blood and sputum — saliva and mucus — of 45 adult CF patients (median age, 35) to determine the levels of BPI-ANCA and to investigate a possible association with lung function, airway inflammation, and bacterial load.

Results showed that 24 patients (53%) were colonized with P. aeruginosa, and 20 (44%) tested positive for BPI-ANCA IgA in their blood. These people had significantly lower forced expiratory volume in one second, a standard measure of lung health, than did BPI-ANCA negative patients.

Chronic infection by P. aeruginosa was also more frequent among patients positive for BPI-ANCA IgA.

“BPI-ANCA has been demonstrated to neutralize the antibacterial effect of BPI [bactericidal/permeability-increasing protein] on E. coli,” the researchers wrote.

“[I]t can be speculated that gram-negative bacteria [like P. aeruginosa] trigger BPI-ANCA expression in the airways, leading to a vicious cycle in which BPI-ANCA neutralizes the antibacterial effect of BPI and weakens mucosal immunity against Pseudomonas and other bacteria,” they added.

A positive correlation between levels of BPI-ANCA IgA in sputum and serum was also observed, with patients positive for this antibody in their blood  having”significantly higher” antibody titers in their airways, the researchers found.

Very low levels of free platelets  were detected in patient sputum, and no significant differences in neutrophil or platelet counts were seen between patients with positive and negative BPI-ANCA in serum.

Neither neutrophil counts, free platelets, nor their complexes correlated with lung function. Neutrophils found in patient sputum also showed no relationship to sputum BPI-ANCA levels. BPI-ANCA levels in the sputum did, however, associate with platelet counts.

Overall “sputum levels of BPI-ANCA IgA correlated with P. aeruginosa DNA and platelet counts in sputum,” the researchers wrote.

Although the significance of platelets in the sputum remains largely unknown, a growing body of evidence from animal models suggests that they affect airway inflammation and infection.

Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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