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Interleukin-33 antibody failed to demonstrate benefit in a phase II, double-blind, randomized, placebo-controlled study in adult patients with moderate-to-severe atopic dermatitis Dear Editor, therapeutic intervention for atopic dermatitis (AD) focuses on neutralizing effector cytokines such as interleukin (IL)-4 and IL-13-1,2 IL-33 is a driver of T helper (Th)2-mediated inflammation and is upstream of IL-4 and IL-13. SP b sp Other race data: placebo [American Indian Alaska Native: I N i (%) 1 (3), missing: 2], 50 mg LY3375880 [Black or African American: 1 (3), missing: 2], 150 mg LY3375880 [Black or African American: 2 (6), missing: 1] and 600 mg LY3375880 [Black or African American: 3 (9)]. [Extracted from the article]

The pathogenesis of atopic dermatitis (AD) results from complex interactions between environmental factors, barrier defects, and immune dysregulation resulting in systemic inflammation. Therefore, we sought to characterize circulating inflammatory profiles in pediatric AD patients and identify potential signaling nodes which drive disease heterogeneity and progression. We analyzed a sample set of 87 infants that were at high risk for atopic disease based on AD diagnoses. Clinical parameters, serum, and peripheral blood mononuclear cells (PBMCs) were collected upon entry, and at 1 and 4 years later. Within patient serum, 126 unique analytes were measured using a combination of multiplex platforms and ultrasensitive immunoassays. We assessed the correlation of inflammatory analytes with AD severity (SCORAD). Key biomarkers, such as IL-13 (rmcorr = 0.47) and TARC/CCL17 (rmcorr = 0.37), among other inflammatory signals, significantly correlated with SCORAD across all timepoints in the study. Flow cytometry and pathway analysis of these analytes implies that CD4 T-cell involvement in type 2 immune responses was enhanced at the earliest time point (year 1) relative to the end of study collection (year 5). Importantly, forward selection modeling identified 18 analytes in infant serum at study entry which could be used to predict change in SCORAD 4 years later. We have identified a pediatric AD biomarker signature linked to disease severity which will have predictive value in determining AD persistence in youth and provide utility in defining core systemic inflammatory signals linked to pathogenesis of atopic disease. [ABSTRACT FROM AUTHOR]

Summary: MSstats is an R package for statistical relative quantification of proteins and peptides in mass spectrometry-based proteomics. Version 2.0 of MSstats supports label-free and label-based experimental workflows and data-dependent, targeted and data-independent spectral acquisition. It takes as input identified and quantified spectral peaks, and outputs a list of differentially abundant peptides or proteins, or summaries of peptide or protein relative abundance. MSstats relies on a flexible family of linear mixed models.Availability and implementation: The code, the documentation and example datasets are available open-source at www.msstats.org under the Artistic-2.0 license. The package can be downloaded from www.msstats.org or from Bioconductor www.bioconductor.org and used in an R command line workflow. The package can also be accessed as an external tool in Skyline (Broudy et al., 2014) and used via graphical user interface.Contact: ovitek@purdue.edu [ABSTRACT FROM AUTHOR]