Role of BARriers in IgG-Pathogen Interactions at the Mucosal Surface in Human Airways

Status: Recruiting
Location: See location...
Intervention Type: Other
Study Type: Interventional
Study Phase: Not Applicable
SUMMARY

Context. Non cystic fibrosis bronchiectasis (NCFB) is a group of suppurative chronic airway diseases of multiple causes. Bronchiectasis is characterized by an abnormal, irreversible dilatation of the bronchi, airway obstruction, chronic cough, and sputum production. Inhaled polyclonal immunoglobulin G (IgG) is a new therapeutic approach for NCFB. Inhaled IgG is expected to have beneficial effects due to its ability to reduce the range of respiratory pathogens capable of infecting the respiratory tract, decrease the pulmonary load of existing bacterial populations, improve mucociliary clearance by restoring epithelial cell functions, and decrease lung inflammation. Pre-clinical data packages showed that IgG reduced the airway pathogen load and related cell damage after infection in rodents and non-human primates. The aim of this study is collect information on the impact of NFCB airway mucus on the biological barriers to locally delivered IgG. Study design. Thirty patients with stable NFCB will be recruited. The patients will provide induced sputum samples after inhaling isotonic saline. Induced sputum will be used for 1) identification of colonizing bacteriological, fungal and virological populations and 2) for in vitro pharmacological experiments. The main outcome is the quantification by whole-cell ELISA of binding to Pseudomonas aeruginosa by a polyclonal IgG in the presence of mucus derived from the sputum of NCFB patients. Secondary outcomes are (1) the measurement of proteolysis, by Western-Blot, of exogenous polyclonal IgG added in the mucus derived from sputum of NCFB patients. The results will be expressed as a percentage of integrity over the one obtained when the polyclonal IgG is added in saline solution and will be compared with in vitro results; (2) the measurement of mobility by Fluorescence Recovery After Photobleaching (FRAP) of exogenous fluorescently-labelled polyclonal IgG added in the mucus derived from sputum of NCFB patients. The results will include the determination of the t(1/2), mobile and immobile fractions over the one obtained when the polyclonal IgG is added in saline solution and will be compared with in vitro results; (3) impact of microbial airway colonization on IgG binding, proteolysis and Ig mobility. Samples with microbial colonization (either bacterial, viral or fungal) will be compared with uncolonized samples. This project will help in decision-making in the development of inhaled antibody therapeutics. Specifically, the study will provide information on the capacity of locally applied polyclonal IgG to diffuse through mucus and bind to pathogens.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Age ≥ 18 years

• Clinical diagnosis of NCFB

• Computed tomography (CT) evidence of bilateral bronchiectasis

• Consent for research use of data and material

• Ability to provide an induced sputum sample

• Stable clinical status over the last 4 weeks

Locations
Other Locations
France
CHRU de Tours
RECRUITING
Tours
Contact Information
Primary
Laurent PLANTIER, MD, PhD
laurent.plantier@univ-tours.fr
+33247476242
Backup
Thomas Secher, PhD
thomas.secher@inserm.fr
+33247366050
Time Frame
Start Date: 2024-12-16
Estimated Completion Date: 2025-12
Participants
Target number of participants: 30
Treatments
Experimental: study group
This is the single arm of this study. Patients with non-CF bronchiectasis will provide 1) an induced sputum sample after inhaling 15 ml of 0.9% NaCl solution and 2) a blood sample.
Sponsors
Leads: University Hospital, Tours

This content was sourced from clinicaltrials.gov