Development Of Atopic March Research Articles

Однонуклеотидний поліморфізм rs510432 гена автофагії 5 та розвиток «атопічного маршу» у дітей

Мета: визначити зв’язок між однонуклеотидним поліморфізмом rs510432 гена автофагії 5 (ATG5) та розвитком «атопічного маршу» у дітей, з’ясувати ймовірність маніфестації клінічних проявів та особливості клінічного перебігу атопічних захворювань в осіб із різними алельними варіантами поліморфізму. Методи. Генотипування поліморфізму rs510432 гена ATG5 у дітей з атопічними захворюваннями та практично здорових дітей із застосуванням методики полімеразної ланцюгової реакції в реальному часі. Результати. Мінорна алель Т rs510432 гена ATG5 вірогідно частіше виявляється у пацієнтів з атопічними захворюваннями, ніж у практично здорових дітей (χ2 = 6,36; р < 0,05). За результатами логістичної регресії ризик розвитку атопічних захворювань у дітей із мінорним генотипом у 2,4 раза вищий, ніж у дітей із мажорним генотипом. Середні значення об’єму форсованого видиху за 1 секунду (ОФВ1) у хворих на бронхіальну астму з мінорним генотипом вірогідно нижчі, ніж з мажорним генотипом (Q = 2,71; р < 0,05). Не виявлено статистично значущих відмінностей у розподілі алельних варіантів поліморфізму rs510432 гена ATG5 залежно від тяжкості бронхіальної астми, атопічного дерматиту та алергічного риніту у дітей. Висновки. У дітей з мінорним генотипом ТТ поліморфізму гена ATG5 виявлено підвищений ризик розвитку атопічних захворювань, що становить 72 %. У хворих на бронхіальну астму мінорний генотип ТТ поліморфізму гена ATG5 асоційований зі зниженим показником ОФВ1. Поліморфізм rs510432 гена ATG5 доцільно використовувати з метою прогнозування розвитку атопічних захворювань у дітей.

Interactions Between Atopic Dermatitis and Staphylococcus aureus Infection: Clinical Implications.

Staphylococcus aureus commonly colonizes the skin of atopic dermatitis (AD) patients and contributes to the development and exacerbation of AD. Multiple factors are associated with colonization of AD skin by S. aureus, including the strength of S. aureus-corneocyte adhesion, deficiency of antimicrobial peptides, decreased levels of filaggrin and filaggrin degradation products, overexpressed Th2/Th17 cytokines, microbial dysbiosis and altered lipid profiles. S. aureus colonization on AD skin causes skin barrier dysfunction through virulence factors such as superantigens (toxins), enzymes and other proteins. Furthermore, colonization of AD skin by S. aureus exacerbates AD and may contribute to microbial dysbiosis, allergen sensitization, Th2/Th17 polarization, development of atopic march and food allergy in AD patients. Skin colonization of S. aureus, particularly methicillin-resistant S. aureus (MRSA), is one of the major challenges commonly encountered in the management of AD. Bleach bath, and topical or systemic antibiotics could be used to control S. aureus infection on AD skin. However, careful use of antibiotics is required to control the occurence of MRSA. Recently, various strategies, including microbiome transplant, monoclonal antibodies against virulent toxins, vaccines and recombinant phage endolysin, have been studied to control S. aureus infection on AD skin. Further advances in our understanding of S. aureus could provide us with ways to manage S. aureus colonization more effectively in AD patients.

FLG P478S polymorphisms and environmental risk factors for the atopic march in Taiwanese children: a prospective cohort study

BackgroundLittle is known about the role of genetic and environmental modifiers in atopic march. ObjectiveTo investigate the effects of filaggrin (FLG) P478S polymorphisms and environmental factors on the risk of asthma in a cohort of children with atopic dermatitis (AD). MethodsIn 2010, 3,246 children from Childhood Environment and Allergic Diseases Cohort Study cohort were recruited. There were 485 children with AD who were invited for further clinical evaluation. Environmental exposures and skin prick tests for allergens were collected at 3 years of age and the development of asthma was determined at 6 years. Multivariate logistic regressions were performed to estimate the association between genetic and environmental factors and the development asthma in children with AD. ResultsOf 397 children with AD who completed the follow-up, 97 developed asthma. After controlling for potential confounders, only mite sensitizations (odds ratio 1.89, 95% confidence interval 1.10–3.25) and the FLG TT genotype (odds ratio 2.26, 95% confidence interval 1.33–3.84) were significantly associated with the development of asthma in children with AD. Mite sensitizations and FLG variants had a synergistic effect on the development of asthma. When children with FLG variants were exposed to mite, the risk for asthma was compounded compared with those with FLG variants without mite exposure (odds ratio 3.58, 95% confidence interval 1.81–7.08). ConclusionMite sensitization and the FLG TT genotype couldt be associated with the development of atopic march.

Epicutaneous Exposure to Staphylococcal Superantigen Enterotoxin B Enhances Allergic Lung Inflammation via an IL-17A Dependent Mechanism

Atopic dermatitis (AD) is the initial step of the atopic march: the progression from AD to allergic rhinitis and asthma. There is a close association between skin barrier abnormalities and the development of AD and the atopic march. One of cardinal features of AD is that the lesional skin of the majority of AD patients is chronically colonized with Staphylococcus aureus with half isolates producing superantigen enterotoxin B (SEB). Although diverse roles of SEB in the pathogenesis and severity of AD have been recognized, whether SEB contributes to the dermal inflammation that drives lung inflammation and airway hyperresponsiveness (AHR) has not been examined. Here we show a novel role of S. aureus superantigen SEB in augmenting allergen ovalbumin (Ova) induced atopic march through an IL-17A dependent mechanism. When mice epicutaneously (EC) sensitized with allergen Ova, addition of topical SEB led to not only augmented systemic Th2 responses but also a markedly exaggerated systemic Th17/IL-17 immune environment. The ability of SEB in enhancing Th17/IL-17 was mediated through stimulating lymphocytes in spleen and draining lymph nodes to promote IL-6 production. Epicutaneous sensitization of mice with a combination of Ova and SEB significantly enhanced Ova-induced AHR and granulocytic lung inflammation than Ova allergen alone. When IL-17A was deleted genetically, the effects of SEB on augmenting lung inflammation and AHR were markedly diminished. These findings suggest that chronic heavy colonization of enterotoxin producing S. aureus in the skin of patients with atopic dermatitis may have an important role in the development of atopic march via an IL-17A dependent mechanism.