Nasal Mucus Proteome and Immunotherapy

Allergic Rhinoconjunctivitis Clinical Trial

Official title:

Seasonal Differences in Nasal Mucus Proteome and Impact of Immunotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02159404
• Other study ID #: ProtOmicsSeasons01
• Secondary ID: KLI 425-B23
• Status: Recruiting
• Start date: April 2015
• Est. completion date: January 1, 2025

Study information

• Verified date: March 2024
• Source: Medical University of Graz
• Contact: Peter V Tomazic, M.D.
• Phone: +4331638581347
• Email: peter.tomazic[@]medunigraz.at
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Nasal mucus as first line defense barrier of the nasal mucosa contains a variety of proteins that act as functional units. We recently showed that the nasal mucus proteome between allergic rhinitis patients and healthy controls is significantly altered. The aim of the present project is to show changes in nasal mucus proteome between allergic rhinitis patients and healthy controls over the pollen and non pollen season and to further determine whether and if so how the proteome changes under immunotherapy. Patients and healthy controls will be enrolled at two time points namely during the pollen season and out of the pollen season. Statistical differences will be determined within the groups and between the groups as well as impact of immunotherapy on patients undergoing therapy. Mucus will be collected with a special suction device equipped with a mucus trap. Then, proteomic analysis will be performed by LC MS/MS mass spectrometry. Database search will identify distinct proteins and their function, origin etc. will be annotated. Protein groups will be analyzed through pathway enrichment and cluster analysis. Furthermore, mechanisms of immunotherapy in responders and success or failure of therapy could be determined. These could lead to the identification of potential biomarkers.

Description:

Nasal mucus as first line defense barrier of the nasal mucosa contains a variety of proteins that act as functional units. We recently showed that the nasal mucus proteome between allergic rhinitis patients and healthy controls is significantly altered. On protein level, immune response in allergic rhinitis is enhanced and barrier function is reduced as reflected by increased epithelial permeability. Moreover, there is an unfavorable imbalance in innate anti-proteases. Proteases in pollen grain could therefore not be adequately deactivated in the mucus further damaging the epithelium which leads to submucosal penetration of allergens and facilitated presentation to antigen presenting cells. The aim of the present project is to show changes in nasal mucus proteome between allergic rhinitis patients and healthy controls over the pollen and non pollen season and to further determine whether and if so how the proteome changes under immunotherapy. For the first aim patients and healthy controls will be enrolled at two time points namely during the pollen season and out of the pollen season. Statistical differences will be determined within the groups and between the groups. The protein changes over the time course reflect how allergics but also healthy controls react to allergen challenge. The results should give insight on possible biomarkers that could be used for diagnostics and therapy. Protein substitution or inhibition may be a future therapy to reinforce the barrier function of nasal mucus and treat allergic rhinitis symptoms. The effect of immunotherapy as sole causal therapy will be determined and therapy responders will be compared to non-responders. We hypothesize that responders will show proteome changes similar to healthy conditions. This further concretizes distinct proteins as biomarkers that could be used as therapeutic agents. Moreover proteome changes could be used to predict and monitor therapeutic success or failure and patients may be stratified to be subjected to other therapeutic strategies than immunotherapy saving time and money. Mucus will be collected with a special suction device equipped with a mucus trap. Then, proteomic analysis will be performed by LC MS/MS mass spectrometry. Database search will identify distinct proteins and their function, origin etc. will be annotated. Protein groups will be analyzed through pathway enrichment and cluster analysis. By this means complex proteomic data can be visualized for a better understanding of global changes in protein networks and functions. Investigating the nasal mucus proteome in diseased and healthy state leads to a better understanding of its barrier function and reaction to allergens. Distinct proteins and/or proteins groups could be used as biomarkers for novel diagnostic and therapeutic approaches. Furthermore, mechanisms of immunotherapy in responders and success or failure of therapy could be determined.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: January 1, 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• pollen allergy verified by skin-prick test, blood tests for specific IgE (RAST) and allergic rhinitis symptoms, eligible for immunotherapy

Exclusion Criteria:

• chronic infectious diseases, bad overall health condition, pregnancy, long-term intake of nasal and/or systemic steroids or antihistamines, acute and/or chronic rhinosinusitis and parallel participation in other studies

Related Conditions & MeSH terms

• Allergic Rhinoconjunctivitis

Intervention

Biological:
• Immunotherapy

Locations

Country	Name	City	State
Austria	ENT University Hospital Graz	Graz	Styria

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

References & Publications (1)

Tomazic PV, Birner-Gruenberger R, Leitner A, Obrist B, Spoerk S, Lang-Loidolt D. Nasal mucus proteomic changes reflect altered immune responses and epithelial permeability in patients with allergic rhinitis. J Allergy Clin Immunol. 2014 Mar;133(3):741-50. doi: 10.1016/j.jaci.2013.09.040. Epub 2013 Nov 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC of protein spectra obtained by mass spectrometry	Areas under the curve of protein spectra will be determined	3 years