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1.
Eur Respir J ; 52(4)2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30190271

RESUMEN

In line with the pathophysiological continuum described between nose and bronchus in allergic respiratory diseases, we assessed whether nasal epithelium could mirror the Type 2 T-helper cell (Th2) status of bronchial epithelium.Nasal and bronchial cells were collected by brushing from healthy controls (C, n=13), patients with allergic rhinitis and asthma (AR, n=12), and patients with isolated allergic rhinitis (R, n=14). Cellular composition was assessed by flow cytometry, gene expression was analysed by RNA sequencing and Th2, Type 17 T-helper cell (Th17) and interferon (IFN) signatures were derived from the literature.Infiltration by polymorphonuclear neutrophils (PMN) in the nose excluded 30% of the initial cohort. All bronchial samples from the AR group were Th2-high. The gene expression profile of nasal samples from the AR group correctly predicted the paired bronchial sample Th2 status in 71% of cases. Nevertheless, nasal cells did not appear to be a reliable surrogate for the Th2 response, in particular due to a more robust influence of the IFN response in 14 out of 26 nasal samples. The Th2 scores in the nose and bronchi correlated with mast cell count (both p<0.001) and number of sensitisations (p=0.006 and 0.002), while the Th17 scores correlated with PMN count (p=0.006 and 0.003).The large variability in nasal cell composition and type of inflammation restricts its use as a surrogate for assessing bronchial Th2 inflammation in AR patients.


Asunto(s)
Asma/inmunología , Rinitis Alérgica/inmunología , Células Th17/citología , Células Th2/citología , Adulto , Asma/fisiopatología , Líquido del Lavado Bronquioalveolar/citología , Estudios de Casos y Controles , Femenino , Expresión Génica , Humanos , Inflamación/inmunología , Interferones/metabolismo , Masculino , Líquido del Lavado Nasal/citología , Mucosa Respiratoria/metabolismo , Rinitis Alérgica/fisiopatología , Análisis de Secuencia de ARN , Células Th17/inmunología , Células Th2/inmunología , Adulto Joven
2.
Toxicol In Vitro ; 32: 248-60, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26795242

RESUMEN

The SENS-IS test protocol for the in vitro detection of sensitizers is based on a reconstructed human skin model (Episkin) as the test system and on the analysis of the expression of a large panel of genes. Its excellent performance was initially demonstrated with a limited set of test chemicals. Further studies (described here) were organized to confirm these preliminary results and to obtain a detailed statistical analysis of the predictive capacity of the assay. A ring-study was thus organized and performed within three laboratories, using a test set of 19 blind coded chemicals. Data analysis indicated that the assay is robust, easily transferable and offers high predictivity and excellent within- and between-laboratories reproducibility. To further evaluate the predictivity of the test protocol according to Cooper statistics a comprehensive test set of 150 chemicals was then analyzed. Again, data analysis confirmed the excellent capacity of the SENS-IS assay for predicting both hazard and potency characteristics, confirming that this assay should be considered as a serious alternative to the available in vivo sensitization tests.


Asunto(s)
Alérgenos/toxicidad , Alternativas a las Pruebas en Animales , Dermatitis por Contacto , Epidermis/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Humanos , Técnicas In Vitro , Laboratorios , Modelos Biológicos , Reproducibilidad de los Resultados
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