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Non-IgE mediated allergic rhinitis due to Dermatophagoides pteronyssinus in patients with variable common immunodeficiency

Grant number: 21/04273-8
Support Opportunities:Regular Research Grants
Duration: February 01, 2023 - January 31, 2025
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Pedro Francisco Giavina-Bianchi Junior
Grantee:Pedro Francisco Giavina-Bianchi Junior
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Cristina Maria Kokron ; Danilo Gois Gonçalves ; Jorge Elias Kalil Filho


Rhinitis is defined as the inflammation of the nasal mucosa, affecting up to 40% of the population. In addition to infectious causes, rhinitis can be etiologically classified into allergic, non-allergic or mixed. Allergic rhinitis corresponds to the main type of non-infectious rhinitis and affects about 10 to 25% of the world population. Local allergic rhinitis is characterized by an allergic response restricted to the nasal mucosa in the absence of evidence of systemic atopy, that is, absence of detection of specific IgE in vivo (skin test) or in vitro (in the serum) and a positive nasal challenge test. Common variable immunodeficiency (CVI) is the most prevalent symptomatic primary immunodeficiency and can cause not only recurrent respiratory infections, but also chronic non-infectious rhinitis. A Brazilian study defined a prevalence of 81.9% of chronic rhinitis in patients with CVI, among whom 43% had a clinical history compatible with allergic rhinitis. However, an allergic etiology was only confirmed by the detection of specific IgE in vivo (skin test) or in vitro (in serum) in 5.6% of them, and the vast majority (86.1%) of patients with CVI had undetectable dosages of Total IgE. Thus, it is possible that the defect in the production of antibodies in CVI impacts the diagnosis of allergic rhinitis and that a mechanism similar to that of local allergic rhinitis exists in the respiratory tracts of these patients, which can be assessed with the nasal provocation test. It is also speculated that house dust mites may trigger a hypersensitivity reaction through mechanisms which are IgE-independent, with the participation of Th2 lymphocytes and their cytokines, and other effector cells such as eosinophils. Objective: Characterization of possible local allergic rhinitis caused by Dermatophagoides pteronyssinus in individuals with CVI. Casuistry and methods: This is a cross-sectional study which will assess a total and consecutive cohort of patients with non-infectious rhinitis and CVI at the Primary Immunodeficiency Outpatient Clinic of the Clinical Immunology and Allergy Department, Hospital das Clínicas, Faculty of Medicine, University of São Paulo. 20 healthy individuals will be considered as a control group, and there will be a group of 20 individuals with allergic rhinitis. The study will consist of two stages. In the first one, the individuals in the control and allergic rhinitis groups will undergo a nasal provocation test (with the aid of visual analog scale and acoustic rhinometry) to determine the best concentration of the extract of Dermatophagoides pteronyssinus to be used in the second stage. In this stage, individuals with CVI and rhinitis will be submitted to the nasal provocation test and to the nasal lavage for measurements of tryptase, specific IgE and eosinophilic cationic protein. At the end of both stages, a biopsy of the nasal mucosa will be offered optionally for anatomopathological, immunohistochemical and molecular evaluation 24 hours after the start of the nasal provocation test. The molecular analysis consists of evaluating the expression of 84 genes associated with inflammatory and allergic airway processes, through real-time polymerase chain reaction. Expected results: Establishment of the existence of hypersensitivity to Dermatophagoides pteronyssinus, possibly not IgE-mediated, in individuals with CVI and rhinitis; and characterization of the process involved in its pathophysiology through biomarkers. (AU)

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