This led the researchers to believe that the epidemiological factors were not solely responsible for determining the clinical severity of AVB by RSV. Thus, genetic characteristics have been studied as an active

risk factor in AVB severity. It has been estimated that there are over 10 million variations in the human genome (polymorphisms), and these may be associated with the clinical variability in diseases such as AVB, which have recently been the object of population studies. In this context, some studies addressing gene variations associated with immune response were performed in severe AVB by RSV. A recent study evaluated 12,346 twins born in Denmark over a period of 10 years, and found an agreement between them regarding hospitalization for RSV. The agreement was 0.66 in homozygous http://www.selleckchem.com/products/Y-27632.html twins and 0.53 in dizygotic ones, estimating a genetic contribution of 16% to 20% for disease severity,50 which contributes to the hypothesis of a genetic factor influencing AVB severity. In

AVB, infection is restricted Vemurafenib supplier to the surface cells of the respiratory epithelium, especially the hair cells of the bronchioles and type 1 pneumocytes in alveoli, and is opposed by the innate and adaptive immune response. RSV is recognized by epithelial cells through receptors specialized in recognition of pathogen-associated molecular patterns, known as pattern recognition receptors (PRRs) in the form of transmembrane molecules termed toll-like receptors (TLRs), present in macrophages

and dendritic cells, which occur in the production of proinflammatory cytokines (Interleukin 6, 8, 10, and 13, tumor necrosis factor, RANTES, CX3CK1) and surfactant proteins. Some of the factors have direct antiviral properties, while others stimulate the activation of natural killer cells, granulocytes, monocytes, and macrophages, initiating the adaptive immune response. The main TLR responsible for the recognition of RSV is TLR4. TLR4 polymorphisms were associated with risk of severe AVB by RSV, but the results have been controversial. A better understanding of this question is important to more effectively identify those infants at risk for more severe find more AVB evolution. The presence of TLR4, Asp299Gly (rs4986790), and Thr399Ile (rs4986791) polymorphisms was verified in 99 infants hospitalized for severe AVB by RSV, 82 outpatients treated for this disease, and 90 healthy adults. TLR4 polymorphisms were more frequent in the group with severe AVB compared to the other two groups, leading the authors to conclude that the presence of TLR4 polymorphisms was associated with higher disease severity.51 Another study evaluated the influence of Asp299Gly and Thr399Ile polymorphisms in TLR4 gene on cytokine production and demonstrated that there was no influence, concluding that the determination of TLR4 gene polymorphisms does not have any benefit in clinical practice.