Yuzaburo Inoue

CD14 –550 C/T, Which Is Related to the Serum Level of Soluble CD14, Is Associated with the Development of Respiratory Syncytial Virus Bronchiolitis in the Japanese Population

BACKGROUND The contribution that genetic polymorphisms of Toll-like receptor (TLR) 4 and of CD14--both of which recognize respiratory syncytial virus (RSV) in the innate immune response--make to RSV bronchiolitis in the Japanese population has not yet been clarified. METHODS This study genotyped 2 TLR4 mutations, Asp299Gly and Thr399Ile, and 2 single-nucleotide polymorphisms (SNPs) of CD14, -550 C/T and -159 C/T, in 54 children with RSV bronchiolitis and in 203 control subjects. CD14 SNPs and the serum level of soluble CD14 (sCD14) also were examined in 67 cord-blood specimens and in serum samples from 73 6-year-old children. RESULTS No TLR4 mutations were found. The frequencies of both the CC genotype and the C allele of CD14 -550 C/T were significantly higher in children with RSV bronchiolitis than in the control subjects. The serum level of sCD14 was significantly higher in children with the CC genotype of CD14 -550 C/T than in those with the CT and TT genotypes. CONCLUSIONS CD14 -550 C/T, which is related to the serum level of sCD14, is associated with the development of RSV bronchiolitis in the Japanese population. This studys results indicate that, in different ethnic groups, different genetic factors contribute to the development of RSV bronchiolitis.

IL‐10 gene polymorphism, but not TGF‐β1 gene polymorphisms, is associated with food allergy in a Japanese population

The regulatory IL‐10 and TGF‐β1 cytokine gene polymorphisms have been associated with allergic diseases in different populations, like Caucasian, Chinese and Indians. We investigated the association between the polymorphisms IL‐10 A−1082G, C−819T, C−627A and TGF‐β1 T+869C, G+915C, C−509T and food allergy in Japanese children. One hundred and eleven children with food allergy and 115 atopic control children without food allergy were recruited. DNA samples from these subjects were genotyped by using PCR. The odds ratio of IL‐10 −1082 AA genotype was 2.5 (95% CI, 1.0–6.4) for food allergy risk when compared with atopic control subjects (p = 0.03). There were no significative differences in the frequency of TGF‐β1 gene polymorphisms between both groups. Our results indicate that IL‐10 A−1082G gene polymorphism is associated with food allergy susceptibility in atopic Japanese children.

Epidemiology of virus-induced wheezing/asthma in children

Wheezing is a lower respiratory tract symptom induced by various viral respiratory infections. Epidemiological studies have revealed the phenotypes of wheezing in early childhood which have different risk factors for the development of asthma among school age children. The major viral species causing wheezing in children include respiratory syncytial virus, rhinovirus, human metapneumovirus and influenza viruses. It has been shown that the impact on the development of asthma is different between those virus species. Moreover, recent studies have also focused on the interaction between virus infection and other risk factors in the development of asthma, such as genetic factors or allergic sensitization. In this review, we summarize the previous findings and discuss how clinicians can effectively intervene in these viral infections to prevent the development of asthma.

No increase in the serum periostin level is detected in elementary school-age children with allergic diseases.

Fig. 1. No differences in the serum levels of periostin were seen between the children with and without allergic diseases. The serum levels of periostin in the children with allergic diseases were not significantly different from those without allergic diseases. The serum levels of periostin in the children were significantly higher than those observed in the healthy adults, regardless of the presence or absence of allergic disDear Editor

Prebiotic consumption in pregnant and lactating women increases IL-27 expression in human milk.

The consumption of probiotics by pregnant and lactating women may prevent the onset of allergic disorders in their children by increasing the concentrations of immunoactive agents such as cytokines in breast milk. Prebiotics such as fructo-oligosaccharides (FOS) increase the number of beneficial organisms such as bifidobacteria. Thus, prebiotics may have an effect similar to that of probiotics. The objective of the present study was to carry out a comprehensive analysis of mRNA expression in human milk cells to identify changes in the concentrations of cytokines in breast milk after the consumption of FOS (4 g × 2 times/d) by pregnant and lactating women. The microarray analysis of human milk cells demonstrated that the expression levels of five genes in colostrum samples and fourteen genes in 1-month breast milk samples differed more than 3-fold between the FOS and control groups (sucrose group). The mRNA expression level of IL-27, a cytokine associated with immunoregulatory function, was significantly higher in 1-month breast milk samples obtained from the FOS group than in those obtained from the control group. In addition, the protein concentrations of IL-27 in colostrum and 1-month breast milk samples were significantly higher in the FOS group than in the control group. In conclusion, the consumption of FOS by pregnant and lactating women increases the production of IL-27 in breast milk. Future studies will address the association of this phenomenon with the onset of allergic disorders in children.

Cytokine biomarker candidates in breast milk associated with the development of atopic dermatitis in 6-month-old infants.

Background: A few studies have reported that the quantity of selected cytokines/chemokines in breast milk might be associated with atopic dermatitis (AD). Using the multiplex cytokine assay system, we examined cytokines/chemokines in human milk in order to identify new biomarkers related to AD. Methods: We recruited 49 infants with or without AD who participated in a birth cohort and measured the concentrations of cytokines/chemokines in the colostrum (collected within 4–5 days after birth) and mature milk (collected at 1 month postpartum) received by the infants. Results: There were significant differences in the concentrations of interleukin (IL)-1β and IL-12p40 in the colostrum, and in those of IL-4, eotaxin, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-α2 and MIP-1α in the mature milk between the milk received by infants who developed AD at the age of 6 months and that received by the control infants. There was weak to moderate correlation between those 6 cytokines/chemokines in mature milk. Atopic history and IgE levels of mothers were not related to cytokine/chemokine concentrations in breast milk. Logistic regression analyses showed that high levels of eotaxin in the mature milk were a risk for the development of AD at 6 months of age. Conclusion: These results suggest that several cytokines/chemokines, especially eotaxin, are potential biomarkers for development of AD in early infancy.

Functional variants in the thromboxane A2 receptor gene are associated with lung function in childhood‐onset asthma

The thromboxane A2 receptor (TBXA2R) gene is associated with asthma, but no functional genetic variations are known to associate with the disease or its related phenotypes.

Low-dose oral methotrexate for the management of childhood Cogan’s syndrome: a case report

Cogan’s syndrome is a rare inflammatory disease characterized by nonsyphilitic ocular interstitial keratitis associated with hearing loss and vestibular impairment. Although systemic corticosteroids are usually used as the standard therapy, hearing ability in most cases gradually deteriorates. We, herein, describe a patient with childhood Cogan’s syndrome who was treated with low-dose oral methotrexate, which successfully helped to taper the doses of the systemic corticosteroids. The serum levels of the complements were good markers for the disease activity in this patient.

Haploinsufficiency of A20 causes autoinflammatory and autoimmune disorders

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Microbiome/microbiota and allergies

Allergies are characterized by a hypersensitive immune reaction to originally harmless antigens. In recent decades, the incidence of allergic diseases has markedly increased, especially in developed countries. The increase in the frequency of allergic diseases is thought to be primarily due to environmental changes related to a westernized lifestyle, which affects the commensal microbes in the human body. The human gut is the largest organ colonized by bacteria and contains more than 1000 bacterial species, called the “gut microbiota.” The recent development of sequencing technology has enabled researchers to genetically investigate and clarify the diversity of all species of commensal microbes. The collective genomes of commensal microbes are together called the “microbiome.” Although the detailed mechanisms remain unclear, it has been proposed that the microbiota/microbiome, especially that in the gut, impacts the systemic immunity and metabolism, thus affecting the development of various immunological diseases, including allergies. In this review, we summarize the recent findings regarding the importance of the microbiome/microbiota in the development of allergic diseases and also the results of interventional studies using probiotics or prebiotics to prevent allergies.