Genetics Association and Epigenetic Changes in COPD

Genome-wide association studies (GWASs) have successfully identified susceptibility loci associated with COPD. The genes mapped on these loci, eg The FAM13A gene (family with sequence similarity 13, member A), provide a new approach to understand the COPD pathology. Furthermore, heavy smoking is reported to correlate with altered methylation and epigenetic changes of multiple genes in small airway cells. These changes have been shown to be associated with the severity of COPD. It is likely that smoking-induced changes in epigenetic control of gene expression result in genetically vulnerable individual’s results in reduced tissue repair, tissue damage and persistent inflammation associated with COPD pathophysiology

No difference in platelet activation or inflammation markers after diets rich or poor in vegetables, berries and apple in healthy subjects

Background: High intake of vegetables and fruits is associated with decreased risk of coronary heart disease. Part of these cardioprotective effects may be mediated via the antithrombotic effects of compounds found in vegetables and fruits, such as flavonoids. Aim of the study: To study the effects of high and low intake of vegetables, berries and apple on platelet function and inflammatory markers. Methods: The study was a randomised, controlled parallel human dietary intervention with healthy female and male volunteers (n = 77, 19–52 y). Nineteen healthy volunteers served as controls. The volunteers consumed one of four strictly controlled isocaloric 6-week diets containing either 810 or 196 g/10 MJ of vegetables, berries and apple and rich either in linoleic acid (11% of energy, en%) or oleic acid (12 en%). Blood and three 24-hour urine samples were collected at the beginning and at the end of the study period for analyses of various markers of platelet function and inflammation. Results: No differences between the treatment groups were seen in platelet count or volume, markers of platelet activation (ex vivo aggregation to ADP and thrombin receptor activating peptide, protein kinase C activity, urinary 2,3-dinor-thromboxane B2 excretion, plasma P-selectin), plasma intercellular adhesion molecule-1, sensitive C-reactive protein, or antiphospholipid antibodies. Conclusions: The results indicate that in healthy volunteers 6-week diets differing markedly in the amounts of vegetables, berries and apple do not differ in their effects on platelets or inflammation.Peer reviewe

Lactose inhibits regulatory T-cell-mediated suppression of effector T-cell interferon-gamma and IL-17 production

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John William Halderman—In Memoriam

INTRODUCTION: The balance between T(H)1, T(H)2, T(H)17, and regulatory T cells has been suggested to be disturbed in type 1 diabetes (T1D). We investigated this balance in peripheral blood mononuclear cells (PBMC) from children at risk of developing T1D and children with T1D. METHODS: We studied PBMC expression levels of markers related to T(H)1 (T-bet, IL-12Rβ(1), IL-12Rβ(2)), T(H)2 (GATA-3, IL-4Rα), T(H)17 (IL-17A), and regulatory T cells (Foxp3, ICOS, and CTLA-4) with real-time polymerase chain reaction from 17 children with T1D, 13 children with β-cell autoimmunity, 15 children with T1D risk-associated human leukocyte antigen (HLA) haplotypes, and 24 healthy, control children. RESULTS: We observed decreased expression levels of GATA-3 by PBMC of healthy children with autoantibodies compared to healthy, control children (p = 0.014) or children with HLA risk alleles (p = 0.032). Children with T1D demonstrated lower expression levels of T-bet, IL-12Rβ(1), and IL-4Rα both at diagnosis and 12 months later. CONCLUSION: We found no indication of aberrant activation of T(H)1, T(H)17, or Treg in peripheral blood from children with or without risk of T1D. The observed immunological differences between children at risk of and with T1D should be considered when immunopathogenesis of β-cell destruction is studied

Exposure to sewage water and the development of allergic manifestations in Finnish children

Background The hygiene hypothesis suggests that a decreased microbial load contributes to an increased risk of allergies. In the Finnish municipality of Nokia, sewage water was accidentally mixed with drinking water for 2 days. We studied the association between exposure and the emergence of allergies in children. Methods Children aged 2-5 years living in the accident area and an age-matched cohort from the control municipality were recruited. Based on the questionnaires, we identified 139 children exposed to the contaminated water and selected age- and sex-matched controls for them (mean age 16.59 months at the time of the accident). Allergic symptoms and diseases were recorded by ISAAC questionnaires and skin prick tests (SPTs) performed 2 and 5 years after the accident. Results SPT positivity at 5 years of follow-up was decreased in the children exposed to the sewage water below 1 year of age (OR 0.311, 95% CI 0.118-0.820; P = 0.019), particularly in children who did not develop gastroenteritis at exposure. In contrast, the children over 1 year of age at the exposure tended more likely to be SPT-positive at 5 years of follow-up (OR 1.997, 95% CI 0.963-4.143; P = 0.070). Conclusions Sewage water exposure during the first year of life, but not later, decreased the risk of IgE sensitization emphasizing the importance of age as a modulator. The modulation of IgE sensitization by the presence of clinical gastroenteritis at the exposure suggests that the nature of microbial load may have importance or alternatively shared host defense mechanisms protect from infection and atopic sensitization.Peer reviewe