👤 M Rosenkranz

Airway inflammation plays a critical role in asthma pathogenesis and pathophysiology, but the molecular pathways contributing to airway inflammation are not fully known, particularly type 2 (T2) inflammation characterized by both eosinophilia and higher fractional exhaled nitric oxide (Feno) levels. We sought to identify genes whose level of expression in epithelial brushing samples were associated with both bronchoalveolar lavage (BAL) eosinophilia and generation of Feno. We performed segmental allergen bronchoprovocation (SBP-Ag) in participants with asthma, then RNA sequencing analyses of BAL cells and brushing samples before and 48 hours after SBP-Ag to identify regulation of eosinophil recruitment and Feno changes. Allergen bronchoprovocation increased Feno levels, which correlated with eosinophilia. Thirteen genes were identified in brushing samples, whose expression changed in response to SBP-Ag and correlated with both airway eosinophilia and Feno levels after SBP-Ag. Among these 13 genes, epithelial cell product CDH26/cadherin-26 contributed to the amplification of T2 inflammation, as reflected by eosinophilia and Feno, and causal mediation analyses with pro-T2 and proeosinophilic cytokine mediators in BAL fluids. Among the genes associated with reduced eosinophilia and Feno, HEY2 is known to enhance cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition, as well as to reduce apoptosis. This unbiased RNA sequencing analysis in participants with allergic asthma revealed several epithelial cell genes, particularly CDH26, that may be critical for the development or augmentation of T2 inflammation in asthma. Show less

The two most prevalent forms of neuronal ceroid lipofuscinosis (NCL) are the juvenile form (Batten disease, CLN3) and late infantile form (Jansky-Bielschowsky disease, CLN2). The aim of this study was to compare quantitative T2-values of brain tissue in CLN2 and CLN3 patients with reference values from age-matched normal subjects. Twenty-three CLN2 (n = 6) and CLN3 (n = 17) patients (m:f = 11:12) underwent MRI examination including a multiecho T2 sequence. Quantitative T2-values were measured in six defined regions of interest (ROIs) in the calculated quantitative T2 maps within the white matter (WM) and gray matter (GM). The extracted quantitative T2-values were compared with reference values from healthy children and young adults. Informed consent was obtained from the patients or their parents for all patients. Statistical analysis revealed elevated quantitative T2-values in nearly all ROIs placed in the WM of the CLN2 patients. In contrast to this finding, no significant differences were found for the quantitative T2-values of the CLN3 patients compared to the age-matched healthy controls in any of the defined WM ROIs. Both groups exhibited no significant alterations of the quantitative T2-values in the GM ROIs compared to the healthy subjects. Alterations of quantitative T2-values in the cerebral WM may not be a reliable sign to confirm the diagnosis in CLN3 patients but could prove valuable for diagnosis confirmation, follow-up examinations, and longitudinal monitoring of the disease progression in CLN2 patients. Show less