Single cell transcriptomics reveal polyclonal memory T cell responses in abacavir patch test positive skin Publication date: Available online 28 September 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Alec James Redwood, Francois Rwandamuriye, Abha Chopra, Shay Leary, Ramesh Ram, Wyatt McDonnell, Katherine Konvinse, Katie White, Rebecca Pavlos, David M. Koelle, Simon Mallal, Elizabeth Phillips

3-year follow-up after peanut food challenges: accidental reactions in allergic children and introduction failure in tolerant children Publication date: Available online 27 September 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Hannah M. Kansen, Thuy-My Le, André C. Knulst, Diana M.W. Gorissen, Cornelis K. van der Ent, Yolanda Meijer, Francine C. van Erp

Diagnostic Interpretation of Genetic Studies in Patients with Primary Immunodeficiency Diseases: A Working Group Report of the Primary Immunodeficiency Diseases Committee of the American Academy of Allergy, Asthma, and Immunology Publication date: Available online 27 September 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Ivan K. Chinn, Alice Chan, Karin Chen, Janet Chou, Morna J. Dorsey, Joud Hajjar, Artemio M. Jongco, Michael D. Keller, Lisa J. Kobrynski, Attila Kumanovics, Monica G. Lawrence, Jennifer W. Leiding, Patricia L. Lugar, Jordan S. Orange, Kiran Patel, Craig D. Platt, Jennifer M. Puck, Nikita Raje, Neil D. Romberg, Maria A. Slack Abstract Genetic testing has become an integral component of the diagnostic evaluation of patients with suspected primary immunodeficiency diseases. Results of genetic testing can have profound impact on clinical management decisions. Clinical providers must therefore demonstrate proficiency in interpreting genetic data. Because of the need for increased knowledge regarding this practice, the American Academy of Allergy, Asthma, and Immunology Primary Immunodeficiency Diseases Committee established a Work Group that reviewed and summarized information concerning appropriate methods, tools, and resources for evaluating variants identified by genetic testing. Strengths and limitations of tests frequently ordered by clinicians were examined. Summary statements and tables were then developed to guide the interpretation process. Finally, the need for research and collaboration was emphasized. Greater understanding of these important concepts will improve the diagnosis and management of patients with suspected primary immunodeficiency diseases.

Persistence of the clinical effect of grass allergen peptide immunotherapy after the second and third grass pollen season Publication date: Available online 27 September 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Anne K. Ellis, Charles W. Frankish, Kristen Armstrong, Lisa Steacy, Mark W. Tenn, Stephen Pawsey, Roderick P. Hafner Abstract Background Grass allergen peptides are in development for the treatment of grass pollen-induced allergic rhinoconjunctivitis(ARC). A previous randomized, placebo-controlled study demonstrated grass allergen peptides significantly improved total rhinoconjunctivitis symptom scores(TRSS) following post-treatment challenges(PTC) to rye grass in an Environmental Exposure Unit(EEU) after one intervening grass pollen season(GPS1). Objective To evaluate the efficacy/safety of four dosing regimens of grass allergen peptides after a second(GPS2) and third(GPS3) intervening grass pollen season in the EEU. Methods Eligible individuals who were randomized in the parent study(GPS1) during the first year of recruitment were invited to participate in GPS2 and GPS3, which took place 1 and 2 years after treatment cessation respectively. Participants were not treated further and both participants and study personnel remained blinded. The primary efficacy endpoint was the change in mean TRSS(reported every 30 minutes) from GPS1 baseline to the follow-up PTC, calculated across all time points over days 2-4 for GPS2, and across hours 1-3 over days 2-4 for GPS3. Secondary efficacy endpoints and safety were also assessed. Results 122 and 85 participants were enrolled in GPS2 and GPS3 respectively. A greater improvement from baseline in mean TRSS at PTC was observed in the 8x6nmolQ2W group compared to placebo in GPS2(-6.0 vs. -3.6, P=.0535) and GPS3(-6.2 vs. -3.6, P=.1128). Similar findings were observed for the 4x12nmolQ2W group at GPS3(-6.4 vs. -3.6, P=.0759). No adverse safety signals were detected. Conclusion Treatment with grass allergen peptides led to an improvement in ARC symptoms after three intervening grass pollen seasons, corresponding to up to 2 years off treatment. Graphical abstract

Non-canonical β2-receptor signaling Publication date: Available online 26 September 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Brian Lipworth, Rory Chan, Chris RuiWen Kuo

Reply Publication date: Available online 26 September 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Blanca Camoretti-Mercado, Richard F. Lockey

IL-33 blockade impacts mediators of persistence and exacerbation in a model of chronic airway inflammation Publication date: Available online 25 September 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Jeanne Allinne, George Scott, Wei Keat Lim, Dylan Birchard, Jonas S. Erjefält, Caroline Sandén, Li-Hong Ben, Amit Agrawal, Navneet Kaur, Jee Hae Kim, Vishal Kamat, Wen Fury, Tammy Huang, Neil Stahl, George D. Yancopoulos, Andrew J. Murphy, Matthew A. Sleeman, Jamie M. Orengo Abstract Background Severe inflammatory airway diseases are associated with inflammation that fails to resolve, leading to structural changes and an overall environment primed for exacerbations. Objective: We sought to identify and inhibit pathways that perpetuate this heightened inflammatory state, as this could lead to therapies that allow for a more quiescent lung, less predisposed to symptoms and exacerbations. Methods Using prolonged exposure to house dust mite (HDM) in mice, we developed a mouse model of persistent and exacerbating airway disease characterized by a mixed inflammatory phenotype. Results We show that lung IL-33 drives inflammation and remodeling beyond the type 2 response classically associated with IL-33 signaling. IL-33 blockade with an IL-33 neutralizing antibody normalized established inflammation, and improved remodeling of both the lung epithelium and lung parenchyma. Specifically, IL-33 blockade normalized persisting and exacerbating inflammatory endpoints, including eosinophilic, neutrophilic and ST2+ CD4+ T cell infiltration. Importantly, we identified a key role for IL-33 in driving lung remodeling, as anti-IL-33 also reestablished the presence of ciliated cells over mucus producing cells and lowered myofibroblast numbers, even in the context of continuous allergen exposure, resulting in improved lung function. Conclusion Overall, this study shows that elevated IL-33 drives a self-perpetuating amplification loop that retains the lung in a state of lasting inflammation and remodeled tissue, primed for exacerbations. Thus, IL-33 blockade may ameliorate symptoms and prevent exacerbations by quelling persistent inflammation and airway remodeling. Graphical abstract

Reply Publication date: Available online 25 September 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Sabine Flicker, Musa Khaitov, Rudolf Valenta

Increased thrombin activatable fibrinolysis inhibitor (TAFI) in chronic rhinosinusitis with nasal polyps Publication date: Available online 25 September 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Yoshimasa Imoto, Atsushi Kato, Tetsuji Takabayashi, Whitney Stevens, James E. Norton, Lydia A. Suh, Roderick G. Carter, Ava R. Weibman, Kathryn E. Hulse, Kathleen E. Harris, Anju T. Peters, Leslie C. Grammer, Bruce K. Tan, Kevin Welch, Stephanie Shintani-Smith, David B. Conley, Robert C. Kern, Shigeharu Fujieda, Robert P. Schleimer Abstract Background Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease subdivided based on presence or absence of nasal polyps (NPs). Histological features of CRS with NPs (CRSwNP) include inflammatory cell infiltration and excessive fibrin deposition in nasal polyps. Thrombin activatable fibrinolysis inhibitor (TAFI) is an enzyme that plays an anti-fibrinolytic role in the body. The significance of TAFI has been documented in chronic inflammatory diseases including chronic lung disease; however, it has not been evaluated in the pathogenesis of NPs. Objective The objective of this study was to evaluate the potential role of TAFI in the pathogenesis of NPs. Methods Nasal lavage fluids were collected from control subjects and patients with CRS. We measured levels of thrombin/anti-thrombin complex (TATc) and TAFI protein by ELISA. Results TATc levels in nasal lavage fluids were significantly increased in patients with CRSwNP and CRS without NPs (CRSsNP) compared with control subjects, and levels of TAFI in nasal lavage fluids were also significantly elevated in CRSwNP subjects compared with control subjects and CRSsNP subjects. There was a significant correlation between levels of TATc and TAFI in nasal lavage fluids. Interestingly, patients with CRS and asthma showed increased TATc and TAFI in nasal lavage fluids compared to CRS without asthma, especially in patients with CRSwNP. Conclusions Elevated TATc and TAFI in nasal passages of patients with CRSwNP might participate in fibrin deposition in NPs and may play a role in the pathogenesis of CRSwNP and asthma.

Does maternal IgG protect infants from allergen-specific IgE sensitization? Publication date: Available online 25 September 2019 Source: Journal of Allergy and Clinical Immunology Author(s): Rob C. Aalberse, Ulrike Gehring, Marjan Tewis, Theo Rispens