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.

Prognostic accuracy of 12 liver staging systems in patients with unresectable hepatocellular carcinoma treated with transarterial chemoembolization.

PURPOSE: The objective of the present study was to rank the most common liver staging systems according to prognostic accuracy in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). MATERIALS AND METHODS: Survival of 172 consecutive patients with unresectable HCC treated with TACE was correlated with the pretreatment Child-Pugh (categoric and nominal), Okuda, Cancer of the Liver Italian Program, Barcelona Clinic Liver Cancer, Model for End-stage Liver Disease, Chinese University Prognostic Index (CUPI), Japanese Integrated Staging, Tumor/Node/Metastasis, Group d'Etude de Traitement du Carcinoma Hepatocellulaire, Liver Cancer Study Group of Japan, and Tokyo staging systems. The systems were ranked according to error reduction in predicting median survival (Kaplan-Meier survival curve and Cox regression analysis). The error reduction was normalized to the error in predicting survival in the absence of a staging system. RESULTS: Median survival was 80 weeks. The error in predicting survival of an unstaged population was 51 weeks. The Child-Pugh nominal, CUPI, and Tokyo scores yielded the largest reduction in survival prediction error, at 20.8%, 21.6%, and 19.6%, respectively. Their actual error measurements in predicting survival were 40.4, 40.0, and 41.0 weeks, respectively. CONCLUSIONS: Child-Pugh nominal, CUPI, and Tokyo scores provide the best prognostic accuracy among the systems studied. However, those of the Tokyo and CUPI methods are artificially enhanced because of their greater number of staging levels. The Child-Pugh nominal liver staging system is the most accurate in predicting survival of patients with unresectable HCC treated with TACE, and it is recommended that it be adopted as the standard for HCC staging in such patients.