Association of recurrent upper respiratory tract infections with low production of oxygen intermediates in children

Abstract Objectives: Upper respiratory tract infections in children generally have significant morbidity and mortality. There is little data available about functional immaturity of the immune system and the child's susceptibility to infections at the beginning of their lives, thus, justifying a more specific immunological analysis. Method: Analysis of hemograms and innate and adaptive immune responses in 95 children between age 1 to 6 years with episodes of recurrent respiratory infections (test group n = 39) and without these episodes (control group n = 56) was carried out. The production of reactive oxygen intermediates by peripheral blood cells stimulated by phorbol myristate acetate was analyzed. Additionally, the number of B lymphocytes, auxiliary T lymphocytes, and cytotoxic cells was determined using flow cytometry. Results: Results from both groups did not show statistically significant differences in red blood cells, total leukocytes count, and the differential neutrophils, eosinophils, basophils, lymphocytes, and monocytes count. The analysis of the number of B lymphocytes, auxiliary T lymphocytes (LTCD4), and cytotoxic cells (LTCD8) also did not show any difference between both groups. However, the production of radical oxygen intermediates was significantly reduced in the test group as compared to the control group (p < 0.05). Conclusions: There was no difference in the analysis of hemograms, leukograms, or the number of lymphocytes, LTCD4, LTCD8, or LTCD19. The reduced production of oxygen intermediates in the affected group suggests that these children's microbicide capacity is compromised, which may be related to their recurrent respiratory infections.

Polymorphisms in the IL17A gene are not involved in the development of preeclampsia in the Brazilian population / Polimorfismos no gene IL17A não estão envolvidos no desenvolvimento de pré-eclâmpsia na população brasileira

ABSTRACT Introduction: Preeclampsia is defined by the development of hypertension associated with proteinuria after the 20th week of gestation in previously normotensive women. IL17A is a potent inducer of tissue inflammation and polymorphisms in the IL17A gene can modulate gene expression and affect the functioning of Th17 cells, strengthening susceptibility to preeclampsia. Objective: To investigate the polymorphisms rs4711998 A>G, rs8193036 C>T and rs2275913 A>G in the IL17A gene in women with preeclampsia. Methods: This is a control case study, composed of 263 women, 89 with preeclampsia and 174 of the control group. The polymorphisms investigated by real time polymerase chain reaction (PCR) allele discrimination technique. The risk of IL17A polymorphisms contributing to preeclampsia was assessed by the inheritance model through logistic regression. Statistical power presented 99.5% for association detection. Statistical significance was defined as p < 0.05. Results: Genotype frequencies as well as multiple logistic regression analysis were not statistically significant for the rs4711998 A>G, rs8193036 C>T and rs2275913 A>G polymorphisms of the IL17A gene. No association was found between any haplotypes of the polymorphisms investigated and the risk of developing PE. Conclusion: There is no association between the allele frequencies, genotype, inheritance models and haplotypes of the rs4711998 A>G, rs8193036 C>T and rs2275913 A>G polymorphisms of the IL17A gene and PE.

RESUMEN Introducción: La preeclampsia (PE) se define como hipertensión arterial asociada a proteinuria después de la semana 20 de gestación en mujeres anteriormente normotensas. La interleucina 17ª (IL17A) es un inductor potente de inflamación tisular y polimorfismos del gen IL17A pueden modular la expresión génica y afectar las funciones de las células Th17, aumentando la susceptibilidad a la PE. Objetivo: Investigar los polimorfismos rs4711998 A>G, rs8193036 C>T y rs2275913 A>G del gen IL17A en pacientes con PE. Métodos: Se realizó un estudio de casos y controles, compuesto por 263 mujeres: 89 diagnosticadas con PE y 174 del grupo de control. Se evaluaron los polimorfismos investigados a partir del ácido desoxirribonucleico (ADN) genómico aislado de la sangre periférica por reacción en cadena de la polimerasa (PCR) en tiempo real para discriminación alélica. El riesgo de los polimorfismos del gen IL17A para la PE fue evaluado según el modelo de herencia empleando regresión logística. El poder estadístico presentó 99,5% para la detección de asociación. Resultados: Las frecuencias genotípicas, así como el análisis de regresión logística múltiple, no fueron estadísticamente significativas para los polimorfismos rs3761549 C>T, rs3761548 A>C y rs2232365 A>G del gen IL17A. Ningún haplotipo de los polimorfismos investigados mostró asociación con el riesgo de desarrollo de PE. Conclusión: No hay asociación entre las frecuencias alélicas y genotípicas, los modelos de herencia y los haplotipos de los polimorfismos rs4711998 A>G, rs8193036 C>T y rs2275913 A>G del gen IL17A y la PE.

RESUMO Introdução: A pré-eclâmpsia (PE) é definida pelo desenvolvimento de hipertensão arterial associada à proteinúria após a semana de gestação em mulheres previamente normotensas. A interleucina 17A (IL17A) é um potente indutor de inflamação tecidual, e polimorfismos no gene IL17A podem modular a expressão gênica e afetar o funcionamento das células Th17, contribuindo para a suscetibilidade à PE. Objetivo: Investigar os polimorfismos rs4711998 A>G, rs8193036 C>T e rs2275913 A>G no gene IL17A em mulheres com PE. Métodos: Trata-se de um estudo do tipo caso-controle, composto por 263 mulheres, sendo 89 diagnosticadas com PE e 174 do grupo-controle. Os polimorfismos investigados foram avaliados a partir do ácido desoxirribonucleico (DNA) genômico extraído do sangue periférico pela técnica de discriminação alélica por reação em cadeia da polimerase (PCR) em tempo real. O risco de os polimorfismos do gene IL17A contribuírem com a PE foi avaliado pelo modelo de herança através da regressão logística. O poder estatístico apresentou 99,5% para a detecção de associação. A significância estatística foi definida como p < 0,05. Resultados: As frequências genotípicas, assim como a análise de regressão logística múltipla, não foram estatisticamente significativas para os polimorfismos rs3761549 C>T, rs3761548 A>C e rs2232365 A>G do gene IL17A. Não foi observada associação entre nenhum dos haplótipos dos polimorfismos investigados e o risco de desenvolvimento de PE. Conclusão: Não há associação entre as frequências alélicas e genotípicas, os modelos de herança e os haplótipos dos polimorfismos rs4711998 A>G, rs8193036 C>T e rs2275913 A>G do gene IL17A e a PE.

High interleukin-4 expression and interleukin-4 gene polymorphisms are associated with susceptibility to human paracoccidioidomycosis

Paracoccidioidomycosis (PCM) is caused by dimorphic fungi from theParacoccidioides brasiliensis complex. Previous studies have demonstrated that the severity of disease is associated with a T-helper 2 immune response characterised by high interleukin (IL)-4 production. In the present study we analysed two polymorphisms in the IL-4gene (-590 C/T and intron-3 microsatellite) in 76 patients with PCM and 73 control subjects from an endemic area. The production of IL-4 by peripheral blood mononuclear cells after antigen or phytohaemagglutinin stimulation was determined by ELISA. A significant correlation was observed between the RP2/RP2 intron-3 genotype and infection with Paracoccidioides sp.(p = 0.011), whereas the RP1/RP1 genotype was correlated with resistance. No significant correlation was observed for the IL-4promoter polymorphism. Furthermore, the low IL-4 expression observed in the control group compared with patients was associated with the RP1/RP1 genotype. These results suggest that IL-4polymorphisms might be associated with the ability of the host to control Paracoccidioides sp.infection. The relevance of this polymorphism is supported by the observation that patients with disease produce high levels of IL-4 following mitogen or antigen stimulation. The IL-4gene is located in the cytokine cluster region of chromosome 5 where other polymorphisms have also been described.