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Bezerra, TA. Evaluation of antiviral immunity in nasal wash of patients with common variable immunodeficiency along with viral rhinosinusitis [thesis]. São Paulo: “Faculdade de Medicina, Universidade de São Paulo”; 2016. INTRODUCTION: Primary immunodeficiencies (PIDs) are a heterogeneous group of genetic disorders that affect immunity and are characterized by relapsing, usually severe infections. Approximately half of the cases are linked to humoral deficiencies, being common variable immunodeficiency (CVID) the most frequent. CVID patients have reduced levels of antibodies; therefore, these patients have recurrent infections in the respiratory tract and approximately 90% had at least one episode of rhinosinusitis (RS). RS installs itself due to the imbalance between the environment and host factors and viral infection is at least 20 times as common as the bacterial infection in normal individuals. OBJECTIVES: (1) Identify the viral agents of rhinosinusitis in patients with CVID and in control individuals on a prospective context; (2) define which cytokines and chemokines are present in the nasal wash and evaluate the expression of genes related to innate and adaptive antiviral immunity in nasal wash of CVID patients and in control individuals. CASES, MATERIALS, AND METHODS: patients with CVID and control individuals were examined at Outpatient Facility of Dermatological Manifestations of Primary Immunodeficiencies and when they presented signs and symptoms of a viral RS. Nasal wash was collected in order to identify respiratory viruses; secretion of cytokines and chemokines were quantified and gene expression of genes related to innate and adaptive antiviral immunity were evaluated. This evaluation was repeated when all individuals previously studied were asymptomatic. RESULTS: From April 2012 to November 2014, 65 samples of nasal wash, 43 samples of 34 control individuals and 22 samples of 14 patients with CVID were collected. Four samples were positive for virus by direct immunofluorescence technique and eighteen samples by PCR. The detected viruses behaved according to the season in which they are normally detected and patients with CVID proportionally had more and longer infections and required more antibiotics than the control group. The evaluation of the production of cytokines and chemokines showed an increased secretion of CXCL10, CXCL8 CCL2, CCL5, IL-6, IL-10, IL-1β and TNF in both groups when they presented acute viral RS. Gene expression was performed by using Real Time PCR. CVID patients showed increased expression of genes related to innate and adaptive antiviral immunity when compared to control individuals presenting acute viral RS. Conversely, when we compared CVID patients and control individuals both without acute infection, we observed a reduction in gene expression in CVID patients. DISCUSSION: The viral rhinosinusitis respected seasonality and CVID patients had proportionally more infections and a worse evolution than the control group. Apparently, there were no significant differences between the groups regarding the release of cytokines and chemokines. The greater magnitude of gene expression variation observed in CVID patients suggests an imbalance of immune response leading to a state of greater local inflammation with consequent greater tissue damage, therefore justifying an increased incidence of complications, increased duration of symptoms and increased viral replication in this group of patients. Descriptors: Sinusitis; Viruses; Common Variable Immunodeficiency; Cytokines; Chemokines; Real-Time Polymerase Chain Reaction; Immunity, Innate; Adaptive Immunity.

Avaliação da imunidade antiviral no lavado nasal de pacientes com imunodeficiência comum variável em vigência de rinossinusites virais