Navegando por Palavras-chave "Sequenciamento Do Exoma Completo"

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    Evento adverso locorregional pós-vacina BCG como sinalizador de defeito genético-molecular associado a um erro inato da imunidade
    (Universidade Federal de São Paulo (UNIFESP), 2021) Monteiro, Sandra Aparecida Moreira Gomes [UNIFESP]; Pinto, Maria Isabel De Moraes [UNIFESP]; Universidade Federal de São Paulo
    Objectives: To describe the frequency of genetic variants associated with monogenic diseases with inborn errors of immunity in children who have had localized adverse events after BCG vaccination. Patients and Methods: Forty-four children (probands) with a history of localized adverse event to the BCG vaccine (BCGitis) who had an indication of specific drug treatment (isoniazid) were selected. For cases with a history of BCGitis in family members, when available, the other affected family members were included. Human immunodeficiency virus (HIV) infection was considered an exclusion criterion. All patients were evaluated with immunological tests, which included immunophenotyping of T, B and NK cells by flow cytometry, evaluation of phagocytic function (dihydro-rodamin test - DHR) and production of IL-12 and IFNg after in vitro stimulation with BCG and IL-12 or IFNg. When necessary, complement tests were performed and humoral immunity was assessed using immunoglobulins. Whole Exome Sequencing (WES) by New Generation Sequencing (NGS) was performed from peripheral blood samples. The exome sequences were filtered for variants in the 344 genes associated with 354 Inborn Errors of Immunity (IEI-Genes) described by the Primary Immunodeficiency Disease Committee of the International Union of Immunological Societies - IUIS. The candidate variants identified after NGS analysis that were selected were then validated by Sanger sequencing. Samples of the parents and/or siblings of the proband, when available, were submitted to Sanger sequencing to study family segregation. Results: Among the 44 probands, 36 were sporadic cases and eight had other cases of BCGitis in their family. Among the sporadic cases, 25/36 (69.4%) presented, besides BCGitis, immunoallergic conditions or other infectious conditions that required hospitalization. Among the sporadic cases, 15/36 (41.7%) presented variants in IEI-genes classified as pathogenic or likely pathogenic. Among familal cases, 6/8 (75%) presented, in addition to BCGitis, immunoalergic conditions or other infectious conditions that required hospitalization and of these, 4/8 (50%) presented variants in IEI-genes classified as probably pathogenic who met inclusion criteria in this analysis. Considering all probands in the initial cohort, 19/44 (43.2%) presented variants classified as pathogenic or likely pathogenic in IEI-genes. Conclusions: Variants in genes related to inborn erros of immunity and classified as pathogenic or likely pathogenic were found in the exoma analysis of 43.2% of the probands who presented a localized adverse event following BCG vaccination. All these variants found may be related to BCGitis, suggesting that these localized adverse events following BCG immunization may be indicative of a molecular defect related to an inborn error of immunity.