Food protein–induced enterocolitis and alpha-1-antitrypsin deficiency Publication date: Available online 4 November 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Andrew A.M. Singer

Conflicting verdicts on peanut OIT from the ICER and FDA Advisory Committee; where do we go from here? Publication date: Available online 1 November 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Thomas Eiwegger, Katherine Anagnostou, Stefania Arasi, Philippe Bégin, Moshe Ben-Shoshan, Kirsten Beyer, Katharina Blumchen, Helen Brough, Jean-Christoph Caubet, Edmond S. Chan, Meng Chen, Sharon Chinthrajah, Carla M. Davis, Anne Des Roches, George Du Toit, Arnon Elizur, Stephen J. Galli, Geir Håland, Karin Hoffmann-Sommergruber, Harold Kim

The TNF-like weak inducer of the apoptosis/fibroblast growth factor–inducible molecule 14 axis mediates histamine and platelet-activating factor–induced subcutaneous vascular leakage and anaphylactic shock Publication date: Available online 31 October 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Nerea Mendez-Barbero, Alma Yuste-Montalvo, Emilio Nuñez-Borque, Bettina M. Jensen, Carmen Gutiérrez-Muñoz, Jaime Tome-Amat, María Garrido-Arandia, Araceli Díaz-Perales, Contanza Ballesteros-Martinez, Jose Julio Laguna, J.M. Beitia, Lars K. Poulsen, Javier Cuesta-Herranz, Luis Miguel Blanco-Colio, Vanesa Esteban Background Anaphylaxis includes mast cell (MC) activation, but less is known about downstream mechanisms (ie, vascular permeability controlled by endothelial cells [ECs]). The TNF-like weak inducer of apoptosis (TWEAK) and its sole receptor, fibroblast growth factor–inducible molecule 14 (Fn14), belong to the TNF superfamily and are involved in proinflammatory responses. Objective We sought to investigate the role of TWEAK/Fn14 axis in anaphylaxis. Methods In vivo vascular permeability and mouse models of passive systemic anaphylaxis (PSA) and active systemic anaphylaxis were applied to wild-type (WT), TWEAK- and Fn14-deficient mice (TWEAK−/− and Fn14−/−, respectively). Primary bone marrow–derived mast cells (BMMCs) and ECs from WT and Fn14−/− or TWEAK−/− mice were studied. The TWEAK/Fn14 axis was also investigated in human samples. Results Mice with PSA and active systemic anaphylaxis had increased Fn14 and TWEAK expression in lung tissues and increased serum soluble TWEAK concentrations. TWEAK and Fn14 deficiencies prevent PSA-related symptoms, resulting in resistance to decreased body temperature, less severe reactions, and maintained physical activity. Numbers of MCs after PSA are similar between genotypes in different tissue regions, such as ear skin and the trachea, tongue, peritoneum, lungs, and bone marrow. Moreover, in vitro studies revealed no differences in degranulation or mediator release between WT and Fn14−/− BMMCs after IgE-FcεRI stimulation. In vivo and in vitro histamine and platelet-activating factor administration increases Fn14 receptor expression in lungs and ECs. Moreover, Fn14 deficiency in ECs maintained in vitro impermeability when stimulated by mediators or activated BMMCs but not by TWEAK−/− BMMCs, indicating that Fn14 is crucial for endothelial barrier function. TWEAK/Fn14 deletion or TWEAK-blocking antibody prevented histamine/platelet-activating factor–induced vascular subcutaneous permeability. Circulating soluble TWEAK levels were increased in patients with anaphylaxis, and plasma from those patients increased Fn14 expression in ECs. Conclusion The TWEAK/Fn14 axis participates in anaphylactic reactions. Inhibition of TWEAK/Fn14 interaction could be efficacious in anaphylaxis therapy. Graphical abstract

Advances in Asthma and Allergic Disease Genetics – Is Bigger Always Better? Publication date: Available online 31 October 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Nathan Schoettler, Elke Rodríguez, Stephan Weidinger, Carole Ober Abstract This review focuses on genome-wide association studies (GWASs) of asthma and allergic diseases published between January 1, 2018 and June 30, 2019. During this time period there were 38 GWASs reported in 19 papers, including the largest performed to date for many of these conditions. Overall, we learned that childhood onset asthma is associated with the most independent loci compared to other defined groups of asthma and allergic disease cases; adult onset asthma and moderate-to-severe asthma are associated with fewer genes, which are largely a subset of those associated with childhood onset asthma. There is significant genetic overlap between asthma and allergic diseases, particularly with respect to childhood onset asthma, which harbors genes that reflect the importance of barrier function biology, and to HLA region genes, which are the most frequently associated genes overall in both groups of diseases. Although the largest GWASs in African American and Latino/Hispanic populations were reported during this period, they are still significantly underpowered compared to studies reported in European ancestry populations, highlighting the need for larger studies, particularly in childhood onset asthma and allergic diseases, in these important populations that carry the greatest burden of disease.

Peanut oral immunotherapy induces blocking antibodies but does not change the functional characteristics of peanut-specific IgE Publication date: Available online 30 October 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Alexandra F. Santos, Louisa K. James, Matthew Kwok, Richard T. McKendry, Katherine Anagnostou, Andrew T. Clark, Gideon Lack

Autoinflammatory disease: New mouse models and therapies Publication date: Available online 30 October 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Hal M. Hoffman

IL-37: A new player in the chronic rhinosinusitis arena Publication date: Available online 28 October 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Nikita Markov, Hans-Uwe Simon

Anaphylactic or tolerant outcomes with IgE Publication date: Available online 28 October 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Toshiaki Kawakami, Yu Kawakami

Untargeted Metabolomic Profiling Identifies Disease-specific Signatures in Food Allergy and Asthma Publication date: Available online 25 October 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Elena Crestani, Hani Harb, Louis-Marie Charbonnier, Jonathan Leirer, Alison Motsinger-Reif, Rima Rachid, Wanda Phipatanakul, Rima Kaddurah-Daouk, Talal A. Chatila Abstract Background Food allergy (FA) affects an increasing proportion of children. for reasons that remain obscure. Novel disease biomarkers and curative treatment options are strongly needed. Objective To apply untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in FA. Methods Mass spectrometry-based untargeted metabolomic profiling was performed on serum samples of children with either FA alone, asthma alone or both FA and asthma as well as healthy pediatric controls. Results In this pilot study FA subjects exhibited a disease-specific metabolomic signature as compared to both control subjects and asthmatics. In particular, FA was uniquely associated with a marked decrease in sphingolipids, as well as a number of other lipid metabolites, in the face of normal frequencies of circulating natural killer T (NKT) cells. Specific comparison of FA and asthmatic subjects revealed differences in the microbiota-sensitive aromatic amino acid and secondary bile acid metabolism. Children with both FA and asthma exhibited a metabolomic profile that aligned with that of FA alone but not asthma. Among children with FA, history of severe systemic reactions and presence of multiple FA were associated with changes in tryptophan metabolites, eicosanoids, plasmalogens, and fatty acids. Conclusions Children with FA display a disease-specific metabolomic profile that is informative of disease mechanisms and severity, and which dominates in the presence of asthma. Lower levels of sphingolipids and ceramides and other metabolomic alterations observed in FA children may reflect the interplay between an altered microbiota and immune cell subsets in the gut. Graphical abstract

Paradigms and Perspectives: EGID Below the Belt Publication date: Available online 24 October 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Robert D. Pesek, Marc E. Rothenberg