Reduced Levels of Lactoferrin in Biofilm-Associated Chronic Rhinosinusitis

Objective/Hypothesis: The diverse antipathogenic action of lactoferrin has been well characterized. In addition, it is the human body's only known antimicrobial peptide with antibiofilm properties. The purpose of this study was to examine the nasal mucosal expression of lactoferrin in the biofilm-mediated disease, chronic rhinosinusitis (CRS). Study Design/Methods: Nasal biopsies from 41 CRS patients and 21 healthy controls were analyzed using confocal scanning laser microscopy (CSLM) and scanning electron microscopy (SEM) for the presence of biofilms. The messenger ribonucleic acid (mRNA) and protein level of lactoferrin in this tissue were also determined by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. Results: Lactoferrin expression in chronic rhinosinusitis patients at both mRNA and protein level was downregulated relative to controls. Biofilm-positive CRS patients showed a much greater reduction in lactoferrin expression than biofilm-negative patients; mRNA median fold change biofilm positive = 0.03 (interquartile range 0.005-0.15) and biofilm-negative CRS median fold change = 0.49 (interquartile range 0.15-0.81) with median lactoferrin protein expression biofilm-positive patients' median lactoferrin protein expression = 32.58 ng/mL (interquartile range 8.67-59.9 ng/mL) and biofilm-negative patients' median lactoferrin expression = 114.40 ng/mL (interquartile range 75.41-163.1 ng/mL). Conclusions: Genetic, transcriptional, or translational deficiencies in lactoferrin synthesis may reduce the functional level of this important antimicrobial/antibiofilm peptide in the nasal secretions of CRS patients, predisposing certain individuals to bacterial colonization, biofilm development, and recalcitrant sinus disease.