Allergy and Clinical Immunology

Baseline sputum eosinophil+neutrophil subgroups’ clinical characteristics and longitudinal trajectories for NHLBI Severe Asthma Research Program (SARP 3) Cohort Publication date: Available online 5 February 2020 Source: Journal of Allergy and Clinical Immunology Author(s): A.T. Hastie, D.T. Mauger, L.C. Denlinger, A. Coverstone, M. Castro, S. Erzurum, N. Jarjour, B.D. Levy, D.A. Meyers, W.C. Moore, B. Phillips, S.E. Wenzel, J.V. Fahy, E. Israel, E.R. Bleecker, NHLBI SARP 3 Investigators

Optimal Identification of Human Conventional and Non-conventional (CRTH2-IL7Rα-) ILC2s Using Additional Surface Markers Publication date: Available online 4 February 2020 Source: Journal of Allergy and Clinical Immunology Author(s): Sucai Liu, Kapil Sirohi, Mukesh Verma, Jerome McKay, Lidia Michalec, Anand Sripada, Tomas Danhorn, Donald Rollins, James Good, Magdalena M. Gorska, Richard J. Martin, Rafeul Alam Abstract Background Human type-2 innate lymphoid cells (ILC2s) are identified by coupled-detection of CRTH2 and IL7Rα on lineage-negative cells. Type-2 cytokine production by CRTH2-IL7Rα- ILCs is unknown. Objective To identify CRTH2-IL7Rα- type-2 cytokine producing ILCs and their disease relevance. Methods We studied human blood and lung ILCs from asthmatic and control subjects by flow cytometry, ELISA, RNA-seq, qPCR, adoptive transfer to mice and measurement of airway hyperreactivity by Flexivent. Results We found that IL5 and IL13 were expressed not only by CRTH2+ but also by CRTH2-IL7Rα+ and CRTH2-IL7Rα- (DN: double negative) human blood and lung cells. All three ILC populations expressed type-2 genes and induced airway hyperreactivity when adoptively transferred to mice. The frequency of type-2 cytokine+ IL7Rα and DN ILCs were similar to that of CRTH2 ILCs in the blood and lung. Their frequency was higher in asthmatic patients compared to disease controls. Transcriptomic analysis of CRTH2, IL7Rα and DN ILCs confirmed the expression of mRNA for type-2 transcription factors in all three populations. Unexpectedly, the mRNA for GATA3 and IL5 correlated better with mRNA for CD30, TNFR2, ICOS, CCR4 and CD200R1 than CRTH2. Using a combination of these surface markers, especially CD30/TNFR2, we identified a previously unrecognized ILC2 population. Conclusions The commonly used surface markers for human ILC2s leave a majority of type-2 cytokine-producing ILC2s unaccounted for. We identified top GATA3-correlated cell-surface expressed genes in human ILCs by RNA-seq. These new surface markers such as CD30 and TNFR2 identified a previously unrecognized human ILC2 population. This ILC2 population is likely to contribute to asthma.

Improving the diagnostic yield for filaggrin; concealed mutations in the Dutch population Publication date: Available online 1 February 2020 Source: Journal of Allergy and Clinical Immunology Author(s): Frank S. van Leersum, Ivo F. Nagtzaam, Carolien N. van Oosterhoud, Stijn A.I. Ghesquiere, Roel R.H.F.J. Brandts, Antoni Gostyński, Peter M. Steijlen, Michel van Geel

Understanding the Asthmatic Response to an Experimental Rhinovirus Infection: Exploring the Effects of Blocking IgE Publication date: Available online 1 February 2020 Source: Journal of Allergy and Clinical Immunology Author(s): Peter W. Heymann, Thomas AE. Platts-Mills, Judith A. Woodfolk, Larry Borish, Deborah D. Murphy, Holliday T. Carper, Mark R. Conaway, John W. Steinke, Lyndsey Muehling, Teague W. Gerald, Joshua L. Kennedy, Anne-Marie Irani, Matthew D. McGraw, Stephen V. Early, Lisa M. Wheatley, Amy P. Adams, Ronald B. Turner Abstract Background Rhinovirus (RV) frequently causes asthma exacerbations among children and young adults who are allergic. The interaction between allergen and RV-induced symptoms and inflammation over time is unclear. Objective To compare the response to an experimental inoculation with RV-16 in allergic asthmatics and healthy controls, and evaluate the effects of administrating omalizumab before and during the infection. Methods Two clinical trials were run in parallel. One compared the response to an experimental inoculation with RV-16 among asthmatics with high levels of total IgE versus healthy controls. The other compared the effects of administering omalizumab versus placebo to asthmatics in a randomized, DBPC-investigation. The primary outcome for both trials compared lower respiratory tract symptoms (LRTS) between study groups over the first 4 days of infection. Results Frequent comparisons of symptoms, lung function and blood eosinophil counts revealed differences that were more pronounced among allergic asthmatics than controls by days 2 and 3 after RV inoculation. Additionally, an augmentation of upper and LRTS scores occurred among the atopic asthmatics versus controls during the resolution of symptoms (p < 0.01 for upper and < 0.001 for LRTS scores).The beneficial effects of administering omalizumab on reducing LRTS and improving lung function were strongest over the first 4 days. Conclusions Lower respiratory tract symptoms and blood eosinophil counts were augmented and lung function reduced among allergic asthmatics early after RV inoculation and increased late in the infection during symptom resolution. The effect of administering omalizumab on the response to RV was most pronounced during the early/innate phase of the infection.

Current perspective of the etiopathogenesis of delayed-type, and T cell-mediated drug related skin diseases Publication date: Available online 1 February 2020 Source: Journal of Allergy and Clinical Immunology Author(s): Marc Vocanson, Dean J. Naisbitt, Jean-François Nicolas

The Potential of microRNAs as Non-invasive Biomarkers in Acute Pediatric Asthma Publication date: Available online 1 February 2020 Source: Journal of Allergy and Clinical Immunology Author(s): Aleksandra Trifunovic, Alan Dombkowski, Daniela Cukovic, Prashant Mahajan

Treatment of severe lichen planus with the JAK inhibitor tofacitinib Publication date: Available online 1 February 2020 Source: Journal of Allergy and Clinical Immunology Author(s): William Damsky, Alice Wang, Brianna Olamiju, Danielle Peterson, Anjela Galan, Brett King

Serum folate metabolites, asthma, and lung function in a nationwide U.S. study Publication date: Available online 1 February 2020 Source: Journal of Allergy and Clinical Immunology Author(s): Yueh-Ying Han, Erick Forno, Franziska Rosser, Juan C. Celedón

Mast cells initiate the vascular response to contact allergens by sensing cell stress Publication date: Available online 1 February 2020 Source: Journal of Allergy and Clinical Immunology Author(s): Anja Hoppe, Konstantinos Katsoulis-Dimitriou, Hanna Edler, Jan Dudeck, Sebastian Drube, Anne Dudeck

Genetics of chronic rhinosinusitis Publication date: Available online 31 January 2020 Source: Journal of Allergy and Clinical Immunology Author(s): Kyle B. Mitts, Eugene H. Chang