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1. Homologous but not heterologous COVID-19 vaccine booster elicits IgG4+ B-cells and enhanced Omicron subvariant binding

Author

Gemma E. Hartley, Holly A. Fryer, Paul A. Gill, Irene Boo, Scott J. Bornheimer, P. Mark Hogarth, Heidi E. Drummer, Robyn E. O’Hehir, Emily S. J. Edwards, and Menno C. van Zelm

Subjects
Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Booster vaccinations are recommended to improve protection against severe disease from SARS-CoV-2 infection. With primary vaccinations involving various adenoviral vector and mRNA-based formulations, it remains unclear if these differentially affect the immune response to booster doses. We examined the effects of homologous (mRNA/mRNA) and heterologous (adenoviral vector/mRNA) vaccination on antibody and memory B cell (Bmem) responses against ancestral and Omicron subvariants. Healthy adults who received primary BNT162b2 (mRNA) or ChAdOx1 (vector) vaccination were sampled 1-month and 6-months after their 2nd and 3rd dose (homologous or heterologous) vaccination. Recombinant spike receptor-binding domain (RBD) proteins from ancestral, Omicron BA.2 and BA.5 variants were produced for ELISA-based serology, and tetramerized for immunophenotyping of RBD-specific Bmem. Dose 3 boosters significantly increased ancestral RBD-specific plasma IgG and Bmem in both cohorts. Up to 80% of ancestral RBD-specific Bmem expressed IgG1+. IgG4+ Bmem were detectable after primary mRNA vaccination, and expanded significantly to 5–20% after dose 3, whereas heterologous boosting did not elicit IgG4+ Bmem. Recognition of Omicron BA.2 and BA.5 by ancestral RBD-specific plasma IgG increased from 20% to 60% after the 3rd dose in both cohorts. Reactivity of ancestral RBD-specific Bmem to Omicron BA.2 and BA.5 increased following a homologous booster from 40% to 60%, but not after a heterologous booster. A 3rd mRNA dose generates similarly robust serological and Bmem responses in homologous and heterologous vaccination groups. The expansion of IgG4+ Bmem after mRNA priming might result from the unique vaccine formulation or dosing schedule affecting the Bmem response duration and antibody maturation.

Published
2024
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2. Validity, reliability, and responsiveness of daily monitoring visual analog scales in MASK‐air®

Author

Bernardo Sousa‐Pinto, Patrik Eklund, Oliver Pfaar, Ludger Klimek, Torsten Zuberbier, Wienczyslawa Czarlewski, Annabelle Bédard, Carsten Bindslev‐Jensen, Anna Bedbrook, Sinthia Bosnic‐Anticevich, Luisa Brussino, Victoria Cardona, Alvaro A. Cruz, Govert deVries, Philippe Devillier, Wytske J. Fokkens, José Miguel Fuentes‐Pérez, Bilun Gemicioğlu, Tari Haahtela, Yunen Rocío Huerta‐Villalobos, Juan Carlos Ivancevich, Inger Kull, Piotr Kuna, Violeta Kvedariene, Désirée E. Larenas Linnemann, Daniel Laune, Michael Makris, Erik Melén, Mário Morais‐Almeida, Ralph Mösges, Joaquim Mullol, Robyn E. O'Hehir, Nikolaos G. Papadopoulos, Ana Margarida Pereira, Emmanuel P. Prokopakis, Fotis Psarros, Frederico S. Regateiro, Sietze Reitsma, Boleslaw Samolinski, Nicola Scichilone, Jane daSilva, Cristiana Stellato, Ana Todo‐Bom, Peter Valentin Tomazic, Sanna Toppila Salmi, Antonio Valero, Arunas Valiulis, Erkka Valovirta, Michiel vanEerd, Maria Teresa Ventura, Arzu Yorgancioglu, Xavier Basagaña, Josep M. Antó, Jean Bousquet, and João Almeida Fonseca

Subjects
allergic rhinitis, mobile health, reliability, responsiveness, visual analog scales, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background MASK‐air® is an app that supports allergic rhinitis patients in disease control. Users register daily allergy symptoms and their impact on activities using visual analog scales (VASs). We aimed to assess the concurrent validity, reliability, and responsiveness of these daily VASs. Methods Daily monitoring VAS data were assessed in MASK‐air® users with allergic rhinitis. Concurrent validity was assessed by correlating daily VAS values with those of the EuroQol‐5 Dimensions (EQ‐5D) VAS, the Control of Allergic Rhinitis and Asthma Test (CARAT) score, and the Work Productivity and Activity Impairment Allergic Specific (WPAI‐AS) Questionnaire (work and activity impairment scores). Intra‐rater reliability was assessed in users providing multiple daily VASs within the same day. Test–retest reliability was tested in clinically stable users, as defined by the EQ‐5D VAS, CARAT, or “VAS Work” (i.e., VAS assessing the impact of allergy on work). Responsiveness was determined in users with two consecutive measurements of EQ‐5D‐VAS or “VAS Work” indicating clinical change. Results A total of 17,780 MASK‐air® users, with 317,176 VAS days, were assessed. Concurrent validity was moderate–high (Spearman correlation coefficient range: 0.437–0.716). Intra‐rater reliability intraclass correlation coefficients (ICCs) ranged between 0.870 (VAS assessing global allergy symptoms) and 0.937 (VAS assessing allergy symptoms on sleep). Test–retest reliability ICCs ranged between 0.604 and 0.878—“VAS Work” and “VAS asthma” presented the highest ICCs. Moderate/large responsiveness effect sizes were observed—the sleep VAS was associated with lower responsiveness, while the global allergy symptoms VAS demonstrated higher responsiveness. Conclusion In MASK‐air®, daily monitoring VASs have high intra‐rater reliability and moderate–high validity, reliability, and responsiveness, pointing to a reliable measure of symptom loads.

Published
2021
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3. Predominantly Antibody-Deficient Patients With Non-infectious Complications Have Reduced Naive B, Treg, Th17, and Tfh17 Cells

Author

Emily S. J. Edwards, Julian J. Bosco, Pei M. Aui, Robert G. Stirling, Paul U. Cameron, Josh Chatelier, Fiona Hore-Lacy, Robyn E. O'Hehir, and Menno C. van Zelm

Subjects
predominantly antibody deficiency, common variable immunodeficiency, autoimmunity, X-linked agammaglobulinemia, follicular helper T cells, CD21lo B cells, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Patients with predominantly antibody deficiency (PAD) suffer from severe and recurrent infections that require lifelong immunoglobulin replacement and prophylactic antibiotic treatment. Disease incidence is estimated to be 1:25,000 worldwide, and up to 68% of patients develop non-infectious complications (NIC) including autoimmunity, which are difficult to treat, causing high morbidity, and early mortality. Currently, the etiology of NIC is unknown, and there are no diagnostic and prognostic markers to identify patients at risk.Objectives: To identify immune cell markers that associate with NIC in PAD patients.Methods: We developed a standardized 11-color flow cytometry panel that was utilized for in-depth analysis of B and T cells in 62 adult PAD patients and 59 age-matched controls.Results: Nine males had mutations in Bruton's tyrosine kinase (BTK) and were defined as having X-linked agammaglobulinemia. The remaining 53 patients were not genetically defined and were clinically diagnosed with agammaglobulinemia (n = 1), common variable immunodeficiency (CVID) (n = 32), hypogammaglobulinemia (n = 13), IgG subclass deficiency (n = 1), and specific polysaccharide antibody deficiency (n = 6). Of the 53, 30 (57%) had one or more NICs, 24 patients had reduced B-cell numbers, and 17 had reduced T-cell numbers. Both PAD–NIC and PAD+NIC groups had significantly reduced Ig class-switched memory B cells and naive CD4 and CD8 T-cell numbers. Naive and IgM memory B cells, Treg, Th17, and Tfh17 cells were specifically reduced in the PAD+NIC group. CD21lo B cells and Tfh cells were increased in frequencies, but not in absolute numbers in PAD+NIC.Conclusion: The previously reported increased frequencies of CD21lo B cells and Tfh cells are the indirect result of reduced naive B-cell and T-cell numbers. Hence, correct interpretation of immunophenotyping of immunodeficiencies is critically dependent on absolute cell counts. Finally, the defects in naive B- and T-cell numbers suggest a mild combined immunodeficiency in PAD patients with NIC. Together with the reductions in Th17, Treg, and Tfh17 numbers, these key differences could be utilized as biomarkers to support definitive diagnosis and to predict for disease progression.

Published
2019
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4. Impaired STAT3-Dependent Upregulation of IL2Rα in B Cells of a Patient With a STAT1 Gain-of-Function Mutation

Author

Menno C. van Zelm, Julian J. Bosco, Pei M. Aui, Samuel De Jong, Fiona Hore-Lacy, Robyn E. O'Hehir, Robert G. Stirling, and Paul U. Cameron

Subjects
chronic mucocutaneous candidiasis, hypogammaglobulinemia, STAT1, gain-of-function, STAT3, IL2Rα, Immunologic diseases. Allergy, RC581-607
Abstract

Heterozygous STAT1 gain-of-function (GOF) mutations form the most common genetic cause of chronic mucocutaneous candidiasis (CMC). In such patients, increased STAT1 function leads to impaired STAT3-dependent activation of IL-17A and IL-17F in T cells, thereby causing impaired Th17 responses to Candida. In spite of the critical role of STAT3 in IL-21 signaling in B cells, nearly all STAT1 GOF patients have normal or high serum IgG. We here present a 44 year-old male with childhood onset of CMC and antibody deficiency since early adulthood. Sequence analysis of STAT1 revealed a heterozygous missense mutation in the coiled-coil domain (p.D168E), which resulted in increased STAT1 phosphorylation of B-cells activated with IFNα and IFNγ. IL-21 induced STAT3 phosphorylation and nuclear localization were normal, but resulted in impaired upregulation of IL2Rα. This newly identified B-cell intrinsic impairment of STAT3 function could underlie the progressive development of hypogammaglobulinemia. Considering the high risk of bronchiectasis and irreversible organ damage, this case illustrates the need for monitoring of IgG levels and/or function in adult patients with STAT1 GOF mutations.

Published
2019
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5. Effects of Extraction Buffer on the Solubility and Immunoreactivity of the Pacific Oyster Allergens

Author

Roni Nugraha, Thimo Ruethers, Elecia B. Johnston, Jennifer M. Rolland, Robyn E. O’Hehir, Sandip D. Kamath, and Andreas L. Lopata

Subjects
allergens, extraction buffer, proteomics, allergenomics, shellfish, immunoreactivity, Chemical technology, TP1-1185
Abstract

Despite recent technological advances, novel allergenic protein discovery is limited by their low abundance, often due to specific physical characteristics restricting their recovery during the extraction process from various allergen sources. In this study, eight different extraction buffers were compared for their ability to recover proteins from Pacific oyster (Crassostrea gigas). The protein composition was investigated using high resolution mass spectrometry. The antibody IgE-reactivity of each extract was determined using a pool of serum from five shellfish-allergic patients. Most of the investigated buffers showed good capacity to extract proteins from the Pacific oyster. In general, a higher concentration of proteins was recovered using high salt buffers or high pH buffers, subsequently revealing more IgE-reactive bands on immunoblotting. In contrast, low pH buffers resulted in a poor protein recovery and reduced IgE-reactivity. Discovery of additional IgE-reactive proteins in high salt buffers or high pH buffers was associated with an increase in allergen abundance in the extracts. In conclusion, increasing the ionic strength and pH of the buffer improves the solubility of allergenic proteins during the extraction process for oyster tissue. This strategy could also be applied for other difficult-to-extract allergen sources, thereby yielding an improved allergen panel for increased diagnostic efficiency.

Published
2021
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6. Delayed Diagnosis and Complications of Predominantly Antibody Deficiencies in a Cohort of Australian Adults

Author

Charlotte A. Slade, Julian J. Bosco, Tran Binh Giang, Elizabeth Kruse, Robert G. Stirling, Paul U. Cameron, Fiona Hore-Lacy, Michael F. Sutherland, Sara L. Barnes, Stephen Holdsworth, Samar Ojaimi, Gary A. Unglik, Joseph De Luca, Mittal Patel, Jeremy McComish, Kymble Spriggs, Yang Tran, Priscilla Auyeung, Katherine Nicholls, Robyn E. O’Hehir, Philip D. Hodgkin, Jo A. Douglass, Vanessa L. Bryant, and Menno C. van Zelm

Subjects
predominantly antibody deficiency, primary immunodeficiency, diagnostic delay, common variable immunodeficiency, X-linked agammaglobulinemia, immunoglobulin subclass deficiency, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundPredominantly antibody deficiencies (PADs) are the most common type of primary immunodeficiency in adults. PADs frequently pass undetected leading to delayed diagnosis, delayed treatment, and the potential for end-organ damage including bronchiectasis. In addition, PADs are frequently accompanied by comorbid autoimmune disease, and an increased risk of malignancy.ObjectivesTo characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia.MethodsWe identified adult patients receiving, or having previously received immunoglobulin replacement therapy for a PAD at four hospitals in metropolitan Melbourne, and retrospectively characterized their clinical and diagnostic features.Results179 patients from The Royal Melbourne, Alfred and Austin Hospitals, and Monash Medical Centre were included in the study with a median age of 49.7 years (range: 16–87 years), of whom 98 (54.7%) were female. The majority of patients (116; 64.8%) met diagnostic criteria for common variable immunodeficiency (CVID), and 21 (11.7%) were diagnosed with X-linked agammaglobulinemia (XLA). Unclassified hypogammaglobulinemia (HGG) was described in 22 patients (12.3%), IgG subclass deficiency (IGSCD) in 12 (6.7%), and specific antibody deficiency (SpAD) in 4 individuals (2.2%). The remaining four patients had a diagnosis of Good syndrome (thymoma with immunodeficiency). There was no significant difference between the age at diagnosis of the disorders, with the exception of XLA, with a median age at diagnosis of less than 1 year. The median age of reported symptom onset was 20 years for those with a diagnosis of CVID, with a median age at diagnosis of 35 years. CVID patients experienced significantly more non-infectious complications, such as autoimmune cytopenias and lymphoproliferative disease, than the other antibody deficiency disorders. The presence of non-infectious complications was associated with significantly reduced survival in the cohort.ConclusionOur data are largely consistent with the experience of other centers internationally, with clear areas for improvement, including reducing diagnostic delay for patients with PADs. It is likely that these challenges will be in part overcome by continued advances in implementation of genomic sequencing for diagnosis of PADs, and with that opportunities for targeted treatment of non-infectious complications.

Published
2018
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7. Synthetic Nanoparticles That Promote Tumor Necrosis Factor Receptor 2 Expressing Regulatory T Cells in the Lung and Resistance to Allergic Airways Inflammation

Author

Rohimah Mohamud, Jeanne S. LeMasurier, Jennifer C. Boer, Je Lin Sieow, Jennifer M. Rolland, Robyn E. O’Hehir, Charles L. Hardy, and Magdalena Plebanski

Subjects
nanoparticles, tumor necrosis factor 2, asthma, PS50G, lung, lymph nodes, Immunologic diseases. Allergy, RC581-607
Abstract

Synthetic glycine coated 50 nm polystyrene nanoparticles (NP) (PS50G), unlike ambient NP, do not promote pulmonary inflammation, but instead, render lungs resistant to the development of allergic airway inflammation. In this study, we show that PS50G modulate the frequency and phenotype of regulatory T cells (Treg) in the lung, specifically increasing the proportion of tumor necrosis factor 2 (TNFR2) expressing Treg. Mice pre-exposed to PS50G, which were sensitized and then challenged with an allergen a month later, preferentially expanded TNFR2+Foxp3+ Treg, which further expressed enhanced levels of latency associated peptide and cytotoxic T-lymphocyte associated molecule-4. Moreover, PS50G-induced CD103+ dendritic cell activation in the lung was associated with the proliferative expansion of TNFR2+Foxp3+ Treg. These findings provide the first evidence that engineered NP can promote the selective expansion of maximally suppressing TNFR2+Foxp3+ Treg and further suggest a novel mechanism by which NP may promote healthy lung homeostasis.

Published
2017
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8. Allergen immunotherapy: Current and new therapeutic strategies

Author

Jennifer M. Rolland and Robyn E. O’Hehir

Subjects
allergen, IgE, immunotherapy, T cell, Immunologic diseases. Allergy, RC581-607
Abstract

Allergen-specific immunotherapy (SIT) involves the administration of gradually increasing amounts of an allergen extract to reduce clinical symptoms of allergy. Well-controlled clinical trials have demonstrated the efficacy of SIT in the treatment of allergic diseases, including rhinoconjunctivitis and asthma, and best practice protocols have been established. Nevertheless, application of this potentially curative treatment is restricted, largely due to the risk of serious adverse events, especially in asthmatics. Although efficacy is high for venom-induced allergy, success rates for the more common aeroallergen-induced disease range from 60 to 80% depending on the allergen. The practice of SIT is currently being refined following major advances in our knowledge of basic immune mechanisms. In particular, new T cell-targeted strategies are being explored with the awareness of the pivotal role allergen-specific T cells play in initiating and regulating the immune response to allergens. Current SIT induces decreased IgE class switching and eosinophil activation by downregulating production of the T helper (Th) 2-type cytokines interleukin (IL)-4 and IL-5. Therefore, allergen preparations that have ablated IgE binding while retaining T cell reactivity should still be clinically effective but have substantially improved safety. These approaches include the use of small peptides based on dominant T cell epitopes of allergens and chemically modified or recombinant allergen molecules. Both approaches have already been tested, with promising results, in animal models; peptide immunotherapy has been shown effective in clinical trials. Defined hypoallergenic molecules or peptides offer ease of standardization in addition to efficacy and safety and will result in more widespread use of SIT in clinical practice. Elucidation of mechanisms for downregulating Th2-predominant responses to allergen by SIT will enable the development of laboratory assays for monitoring clinical efficacy.

Published
2002
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11. Phenotypic Distinctions Between Omega-5-Gliadin Allergy and Peanut Allergy: Clinical Profile, Reaction Rates and Triggers, and Quality of Life

Author

Celia M Zubrinich, Robert M Puy, Robyn E O'Hehir, and Mark Hew

Subjects
Pulmonary and Respiratory Medicine, Journal of Asthma and Allergy, Immunology and Allergy
Abstract

Celia M Zubrinich,1,2 Robert M Puy,3 Robyn E O’Hehir,1,3 Mark Hew1,2 1Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia; 2School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia; 3Allergy and Clinical Immunology Laboratory, Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaCorrespondence: Celia M Zubrinich, Email c.zubrinich@alfred.org.auBackground: Different phenotypes of food allergy may exist, exhibiting distinct clinical features, and driven by different pathogenic mechanisms. We compared omega-5-gliadin (O5G) allergy to peanut allergy, focusing on clinical features, reaction rates and triggers, and quality of life (QOL).Methods: We surveyed adults with O5G allergy and peanut allergy regarding their diagnosis, co-morbidities, allergic reactions, and QOL measured by the FAQLQ-AF.Results: We received responses from 43/80 (54%) individuals with O5G allergy and 43/130 (33%) with peanut allergy. Compared to peanut allergic individuals, those with O5G allergy were older at age of onset (37.2 vs 2.5 years, p < 0.001), had fewer additional atopic conditions (0.88 vs 2.93, p < 0.001) or food allergies (0.15 vs 1.86, p < 0.001), and more frequent reactions before diagnosis (1.085 vs 0.29 per month, p < 0.05) Reaction rates improved in both groups following diagnosis. Reactions to peanut were more often triggered by accidental exposure (84% vs 26%, p < 0.001) and being away from home (65% vs 28%, p < 0.001), while reactions to O5G were more often due to deliberate ingestion (30% vs 9%, p < 0.05) or unexpected exercise (35% vs 2%, p < 0.001). Overall QOL score was similar between groups (4.2 in O5G allergy, 4.7 in peanut allergy, p = 0.12), but worse among women and those with additional food allergies.Conclusion: Phenotypic differences between O5G and peanut allergy support the development of different clinical approaches and the possibility of targeting distinct pathogenic mechanisms for prevention and treatment. Quality of life was impaired to a similar degree between groups.Keywords: omega-5-gliadin allergy, wheat allergy, peanut allergy, food allergy, anaphylaxis, wheat-dependent exercise-induced allergy, WDEIA, food-dependent exercise-induced allergy, FDEIA, quality of life, QOL, Australia

Published
2022

12. Humoral immunity and B-cell memory in response to SARS-CoV-2 infection and vaccination

Author

Holly A. Fryer, Gemma E. Hartley, Emily S.J. Edwards, Robyn E. O'Hehir, and Menno C. van Zelm

Subjects
Ad26COVS1, Memory B Cells, SARS-CoV-2, Vaccination, Humans, COVID-19, Antibodies, Neutralizing, Biochemistry, BNT162 Vaccine, Immunity, Humoral
Abstract

Natural infection with SARS-CoV-2 induces a robust circulating memory B cell (Bmem) population, which remains stable in number at least 8 months post-infection despite the contraction of antibody levels after 1 month. Multiple vaccines have been developed to combat the virus. These include two new formulations, mRNA and adenoviral vector vaccines, which have varying efficacy rates, potentially related to their distinct capacities to induce humoral immune responses. The mRNA vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) elicit significantly higher serum IgG and neutralizing antibody levels than the adenoviral vector ChAdOx1 (AstraZeneca) and Ad26.COV2.S (Janssen) vaccines. However, all vaccines induce Spike- and RBD-specific Bmem, which are vital in providing long-lasting protection in the form of rapid recall responses to subsequent infections. Past and current SARS-CoV-2 variants of concern (VoC) have shown the capacity to escape antibody neutralization to varying degrees. A booster dose with an mRNA vaccine following primary vaccination restores antibody levels and improves the capacity of these antibodies and Bmem to bind viral variants, including the current VoC Omicron. Future experimental research will be essential to evaluate the durability of protection against VoC provided by each vaccine and to identify immune markers of protection to enable prognostication of people who are at risk of severe complications from COVID-19.

Published
2022

17. COVID-19 adenoviral vector vaccination elicits a robust memory B cell response with the capacity to recognize Omicron BA.2 and BA.5 variants

Author

Holly A. Fryer, Gemma E. Hartley, Emily S.J. Edwards, Nirupama Varese, Irene Boo, Scott J. Bornheimer, P. Mark Hogarth, Heidi E. Drummer, Robyn E. O’Hehir, and Menno C. van Zelm

Abstract

Following the COVID-19 pandemic caused by SARS-CoV-2, novel vaccines have successfully reduced severe disease and death. Despite eliciting lower antibody responses, adenoviral vector vaccines are nearly as effective as mRNA vaccines. Therefore, protection against severe disease may be mediated by immune memory cells. We here evaluated plasma antibody and memory B cells (Bmem) targeting the Spike receptor binding domain (RBD) elicited by the adenoviral vector vaccine ChAdOx1 (AstraZeneca), their capacity to bind Omicron subvariants, and compared this to the response elicited by the mRNA vaccine BNT162b2 (Pfizer-BioNTech). Whole blood was sampled from 31 healthy adults pre-vaccination, and four weeks after dose one and dose two of ChAdOx1. Neutralizing antibodies (NAb) against SARS-CoV-2 were quantified at each timepoint. Recombinant RBDs of the Wuhan-Hu-1 (WH1), Delta, BA.2, and BA.5 variants were produced for ELISA-based quantification of plasma IgG and incorporated separately into fluorescent tetramers for flow cytometric identification of RBD-specific Bmem. NAb and RBD-specific IgG levels were over eight times lower following ChAdOx1 vaccination than BNT162b2. In ChAdOx1-vaccinated individuals, median plasma IgG recognition of BA.2 and BA.5 as a proportion of WH1-specific IgG was 26% and 17%, respectively. All donors generated resting RBD-specific Bmem, which were boosted after the second dose of ChAdOx1, and were similar in number to those produced by BNT162b2. The second dose of ChAdOx1 boosted Bmem that recognized VoC, and 37% and 39% of WH1-specific Bmem recognized BA.2 and BA.5, respectively. These data uncover mechanisms by which ChAdOx1 elicits immune memory to confer effective protection against severe COVID-19.

Published
2023

19. Management of anaphylaxis due to COVID-19 vaccines in the elderly

Author

Paulo Augusto Moreira Camargos, Radolslaw Gawlik, Mirko Petrovic, Gunter J. Sturm, Kristof Nekam, Sergio Bonini, Zhanat Ispayeva, Marilyn Urrutia Pereira, Jean Bousquet, Antti Lauerma, Menachem Rottem, Arzu Yorgancioglu, Hubert Blain, Antonio Cherubini, Mário Morais-Almeida, Nathalie Salles, Charlotte G. Mortz, Sylwia Smolinska, Davor Plavec, A. Bedbrook, Torsten Zuberbier, Helga Kraxner, M. Beatrice Bilò, Sinthia Bosnic-Anticevich, Gaëtan Gavazzi, Finbarr C. Martin, Alvaro A. Cruz, K. S. Bennoor, Isabella Annesi-Maesano, Mohamed H. Shamji, Karin Hoffmann-Sommergruber, Marina Atanaskovic-Markovic, Carsten Bindslev-Jensen, Lan Tt Le, Isabel Skypala, Ana Todo-Bom, Vincenzo Patella, Lorenzo Cecchi, Charlotte Suppli Ulrik, Oscar Palomares, Joaquin Sastre, Hans Jürgen Hoffmann, Knut Brockow, Eva Untersmayr, Martin Hrubisko, Bernadette Eberlein, Aziz Sheikh, Milan Sova, Osman M. Yusuf, Violeta Kvedariene, G. Walter Canonica, Dana Wallace, Ioana Agache, Milena Sokolowska, Jos M. G. A. Schols, Susan Waserman, Stéphanie Miot, Carla Irani, Regina E Roller-Winsberger, Michael Levin, Yves Rolland, Emma Montella, Bilun Gemicioglu, Bolesław Samoliński, Stefano Del Giacco, Madda lenaIllario, Yehia El-Gamal, Olga Lourenço, Jean-Christoph Roger J-P Caubet, Luisa Brussino, Marysia Recto, De Yun Wang, Igor Kaidashev, Renaud Louis, Antonino Romano, Mario E. Zernotti, Jacques Reynes, Pedro Carreiro-Martins, Alexandra F. Santos, Marek Niedoszytko, M. Gotua, Musa Khaitov, Thomas B. Casale, Andrea Matucci, Bernardo Sousa-Pinto, Rafael Stelmach, Dejan Dokic, Joana Vitte, Motohiro Ebisawa, Maria Teresa Ventura, Joaquim Mullol, Tomas Chivato, Petr Panzner, Oliver Pfaar, Sanna Toppila-Salmi, Ioanna Tsiligianni, Wytske Fokkens, Alessandra Vultaggio, H. Neffen, Juan Carlos Ivancevich, Ya-dong Gao, Anna Sediva, Maja Hofmann, Ana Maria Carriazo, João Fonseca, Marek Jutel, A. Benetos, Nhân Pham-Thi, Mona Al-Ahmad, Arunas Valiulis, Mihaela Zidarn, Elizabeth Angier, Yoshitaka Okamoto, Montserrat Fernandez-Rivas, Cezmi A. Akdis, Philip W. Rouadi, Olivier Guérin, John Farrell, Mikaela Odemyr, George Christoff, Vera Mahler, Claus Bachert, Edward F. Knol, Wienczyslawa Czarlewski, Robyn E O'Hehir, Victoria Cardona, Ludger Klimek, Tari Haahtela, Vincent Le Moing, Branislava Milenkovic, Carmen Rondon, Kaja Julge, Jolanta Walusiak-Skorupa, Nikolaos G. Papadopoulos, Aslı Gelincik, Markus Ollert, Piotr Kuna, Leyla Namazova-Baranova, Margitta Worm, Annick Barbaud, Elena Camelia Berghea, Todor A. Popov, Derek K. Chu, María José Torres, Faradiba Sarquis Serpa, Nicola Scichilone, Amir Hamzah Abdul Latiff, Frederico S. Regateiro, Gianni Passalacqua, Humboldt-Universität zu Berlin, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Humboldt University Of Berlin, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Transylvania University, Wrocław Medical University, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of Cagliari, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Università Politecnica delle Marche [Ancona] (UNIVPM), Medical Consulting Czarlewski, Universiti Putra Malaysia, University of Southampton, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Belgrade [Belgrade], Ghent University Hospital, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Dhaka Shishu Hospital [Bangladesh], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Odense University Hospital (OUH), Italian National Research Council, National Research Council [Italy] (CNR), The University of Sydney, Technische Universität München = Technical University of Munich (TUM), Università degli studi di Torino = University of Turin (UNITO), Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), IRCCS Research Hospital, Milan, Vall d'Hebron University Hospital [Barcelona], Centro Hospitalar de Lisboa Central E.P.E, University of South Florida [Tampa] (USF), Geneva University Hospital (HUG), Azienda Usl Toscana centro [Firenze], Софийски университет = Sofia University, McMaster University [Hamilton, Ontario], State University of Bahia, Institute of Public Health of Republic of North Macedonia [Skopje], Ain Shams University (ASU), Sagamihara National Hospital [Kanagawa, Japan], Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Amsterdam UMC - Amsterdam University Medical Center, Universidade do Porto = University of Porto, Wuhan University [China], CHU Grenoble, Silesian University of Medicine, Istanbul Faculty of Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Centre Hospitalier Universitaire de Nice (CHU Nice), Helsinki University Hospital [Helsinki, Finlande], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Medizinische Universität Wien = Medical University of Vienna, Aarhus University [Aarhus], Oncology Institute of St Elisabeth, University of Naples Federico II = Università degli studi di Napoli Federico II, St Joseph University, Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Kazakh National Medical University, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Tartu University Institute of Clinical Medicine, Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Federal Medicobiological Agency [Moscow, Russian Federation], University Medical Center [Utrecht], Semmelweis University [Budapest], Medical University of Łódź (MUL), Vilnius University [Vilnius], University of Medicine and Pharmacy (VIETNAM), University of Cape Town, CHU Sart Tilman, Université de Liège, University of Beira Interior [Portugal] (UBI), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), uBibliorum, Ear, Nose and Throat, AII - Inflammatory diseases, CHU Montpellier, Wroclaw Medical University [Wrocław, Pologne], University of Bari Aldo Moro (UNIBA), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sagamihara National Hospital, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Toulouse [Toulouse], RS: CAPHRI - R1 - Ageing and Long-Term Care, Health Services Research, Bousquet J., Agache I., Blain H., Jutel M., Ventura M.T., Worm M., Del Giacco S., Benetos A., Bilo B.M., Czarlewski W., Abdul Latiff A.H., Al-Ahmad M., Angier E., Annesi-Maesano I., Atanaskovic-Markovic M., Bachert C., Barbaud A., Bedbrook A., Bennoor K.S., Berghea E.C., Bindslev-Jensen C., Bonini S., Bosnic-Anticevich S., Brockow K., Brussino L., Camargos P., Canonica G.W., Cardona V., Carreiro-Martins P., Carriazo A., Casale T., Caubet J.-C., Cecchi L., Cherubini A., Christoff G., Chu D.K., Cruz A.A., Dokic D., El-Gamal Y., Ebisawa M., Eberlein B., Farrell J., Fernandez-Rivas M., Fokkens W.J., Fonseca J.A., Gao Y., Gavazzi G., Gawlik R., Gelincik A., Gemicioglu B., Gotua M., Guerin O., Haahtela T., Hoffmann-Sommergruber K., Hoffmann H.J., Hofmann M., Hrubisko M., Illario M., Irani C., Ispayeva Z., Ivancevich J.C., Julge K., Kaidashev I., Khaitov M., Knol E., Kraxner H., Kuna P., Kvedariene V., Lauerma A., Le L.T.T., Le Moing V., Levin M., Louis R., Lourenco O., Mahler V., Martin F.C., Matucci A., Milenkovic B., Miot S., Montella E., Morais-Almeida M., Mortz C.G., Mullol J., Namazova-Baranova L., Neffen H., Nekam K., Niedoszytko M., Odemyr M., O'Hehir R.E., Okamoto Y., Ollert M., Palomares O., Papadopoulos N.G., Panzner P., Passalacqua G., Patella V., Petrovic M., Pfaar O., Pham-Thi N., Plavec D., Popov T.A., Recto M.T., Regateiro F.S., Reynes J., Roller-Winsberger R.E., Rolland Y., Romano A., Rondon C., Rottem M., Rouadi P.W., Salles N., Samolinski B., Santos A.F., S Sarquis F., Sastre J., M. G. A. Schols J., Scichilone N., Sediva A., Shamji M.H., Sheikh A., Skypala I., Smolinska S., Sokolowska M., Sousa-Pinto B., Sova M., Stelmach R., Sturm G., Suppli Ulrik C., Todo-Bom A.M., Toppila-Salmi S., Tsiligianni I., Torres M., Untersmayr E., Urrutia Pereira M., Valiulis A., Vitte J., Vultaggio A., Wallace D., Walusiak-Skorupa J., Wang D.-Y., Waserman S., Yorgancioglu A., Yusuf O.M., Zernotti M., Zidarn M., Chivato T., Akdis C.A., Zuberbier T., Klimek L., HUS Inflammation Center, University of Helsinki, and Department of Dermatology, Allergology and Venereology

Subjects
Male, Allergy, Pediatrics, Eaaci Position Paper, COVID-19 vaccines, older (adults, GUIDELINES, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Immunology and Allergy, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Geriatrics, MESH: Aged, RISK, Vaccines, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, people), EPINEPHRINE, Epinephrine, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, COVID -19 vaccines, Anaphylaxis, medicine.drug, older (adults/people), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), MESH: Covid-19, MESH: Epinephrine, Immunology, adrenaline, anaphylaxis, Aged, COVID-19 Vaccines, Humans, SARS-CoV-2, COVID-19, Settore MED/10 - Malattie Dell'Apparato Respiratorio, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes mellitus, Anaphylaxis/etiology, MESH: SARS-CoV-2, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, COVID‐19 vaccines, Older - Adults/people, Asthma, MESH: Humans, business.industry, adrenaline, anaphylaxis, COVID-19 vaccines, older (adults/people), medicine.disease, Obesity, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH: Anaphylaxis, Older, 3121 General medicine, internal medicine and other clinical medicine, business, MESH: Covid-19 vaccines, 030215 immunology
Abstract

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Published
2021

20. Vaccines and Allergic reactions: The past, the current COVID-19 pandemic, and future perspectives

Author

Domingo Barber, Robyn E O'Hehir, Mihir Shah, Ronald L. Rabin, Markus Ollert, Wytske Fokkens, Oliver Pfaar, Menno C. van Zelm, Luo Zhang, Milena Sokolowska, Mübeccel Akdis, De Yun Wang, Cezmi A. Akdis, Thomas Eiwegger, Katharine Fast, Claudia Traidl-Hoffmann, Heimo Breiteneder, Zuzana Diamant, Ioana Agache, Kari C. Nadeau, Milos Jesenak, Mohamed H. Shamji, María José Torres, Vanitha Sampath, Stefan Vieths, Carmen Riggioni, Liam O'Mahony, Oscar Palomares, Grace Rabinowitz, Sharon Chinthrajah, William Collins, Surabhi Jain, and Tomas Chivato

Subjects
0301 basic medicine, Allergy, CHILDREN, Review Article, HYPERSENSITIVITY REACTIONS, SARS‐CoV‐2, 0302 clinical medicine, allergy, vaccine, Pandemic, Immunology and Allergy, PROTEIN-COUPLED RECEPTOR-X2, Review Articles, anaphylaxis, Vaccines, SARS-CoV-2, Vaccination, Safety profile, VACCINATION, COVID-19, Anaphylaxis, medicine.medical_specialty, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Hypersensitivity/diagnosis, Immunology, 03 medical and health sciences, COVID‐19, medicine, Hypersensitivity, Vaccines/adverse effects, Humans, MAST-CELL, Intensive care medicine, Pandemics, business.industry, Public health, GELATIN, ANTI-PEG ANTIBODIES, medicine.disease, 030104 developmental biology, 030228 respiratory system, Infectious disease (medical specialty), ADVERSE-REACTIONS, SAFETY DATA, business
Abstract

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.

Published
2021

21. RNA sequencing of single allergen-specific memory B cells after grass pollen immunotherapy: Two unique cell fates and CD29 as a biomarker for treatment effect

Author

Craig I. McKenzie, Nirupama Varese, Pei Mun Aui, Simone Reinwald, Bruce D. Wines, P. Mark Hogarth, Francis Thien, Mark Hew, Jennifer M. Rolland, Robyn E. O'Hehir, and Menno C. van Zelm

Subjects
Immunology, Immunology and Allergy
Abstract

Sublingual immunotherapy (SLIT) for grass pollen allergy can modify the natural history of allergic rhinitis and is associated with increased allergen-specific IgGBlood samples were collected twice outside the pollen season from twenty-seven patients with sensitization to ryegrass pollen (RGP; Lolium perenne) and seasonal rhinoconjunctivitis. Thirteen received 4-month pre-seasonal SLIT for grass pollen allergy, and 14 received standard pharmacotherapy only. Single-cell RNA sequencing was performed on FACS-purified Lol p 1-specific Bmem before and after SLIT from four patients, and significant genes were validated by flow cytometry on the total cohort.Four months of SLIT increased RGP-specific IgE and IgGA clinically successful 4 months course of SLIT for grass pollen allergy induces two transcriptionally unique Bmem fates. Associated changes in surface-expressed proteins on these Bmem subsets can be used as early biomarkers for treatment effects.

Published
2022

22. New insights into human immune memory from SARS-CoV-2 infection and vaccination

Author

Gemma E. Hartley, Emily S. J. Edwards, Robyn E. O’Hehir, and Menno C. van Zelm

Subjects
SARS-CoV-2, Immunology, Vaccination, Immunology and Allergy, Humans, COVID-19, Immunologic Memory, Pandemics
Abstract

Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS-CoV-2 and emerging variants resulting in mass morbidity and an estimated 6 million deaths globally. The scientific community pivoted rapidly, providing unique and innovative means to identify infected individuals, technologies to evaluate immune responses to infection and vaccination, and new therapeutic strategies to treat infected individuals. Never before has immunology been so critically at the forefront of combatting a global pandemic. It has now become evident that not just antibody responses, but formation and durability of immune memory cells following vaccination are associated with protection against severe disease from SARS-CoV-2 infection. Furthermore, the emergence of variants of concern (VoC) highlight the need for immunological markers to quantify the protective capacity of Wuhan-based vaccines. Thus, harnessing and modulating the immune response is key to successful vaccination and treatment of disease. We here review the latest knowledge about immune memory generation and durability following natural infection and vaccination, and provide insights into the attributes of immune memory that may protect from emerging variants.

Published
2022

23. Double-dose mRNA vaccination to SARS-CoV-2 progressively increases recognition of variants-of-concern by Spike RBD-specific memory B cells

Author

Gemma E. Hartley, Emily S.J. Edwards, Nirupama Varese, Irene Boo, Pei M. Aui, Scott J. Bornheimer, P. Mark Hogarth, Heidi E. Drummer, Robyn E. O’Hehir, and Menno C. van Zelm

Abstract

BackgroundSARS-CoV-2 vaccination with BNT162b2 (Pfizer BioNTech) has been shown to be 95% effective.1 Double-dose vaccination generates high levels of spike-specific antibodies, memory B cells (Bmem) and T cells. However, variants of concern (VoC) with mutations in the spike Receptor Binding Domain (RBD) can evade antibody responses. Booster vaccinations improve antibody recognition of VoC, but it is unclear if this is due to higher total antibodies or their capacity to bind VoC. We here addressed the capacity of surface Ig on single Wuhan-specific Bmem after first and second dose BNT162b2 vaccination to recognize variant RBD.MethodsSamples were collected from 30 healthy COVID-19 naive individuals pre-BNT162b2 vaccination, 3 weeks post-dose 1 and 4-weeks post-dose 2. Plasma antibodies and Bmem were evaluated using recombinant RBD proteins of the Wuhan, Gamma and Delta strains.ResultsAll individuals generated a robust antibody response to BNT162b2 vaccination with all participants producing neutralizing antibodies following dose 2. IgM+ and IgG+ RBD-specific Bmem were generated after one vaccine dose, and those expressing IgG1 increased in absolute number after dose 2. The majority of RBD-specific Bmem bound the Gamma and/or Delta variants, and this proportion significantly increased after the second dose.ConclusionThe second dose of BNT162b2 increases the number of circulating Ig-class switched RBD-specific Bmem. Importantly, the second dose of vaccination is required for a high frequency of RBD-specific Bmem to recognize Gamma and Delta variants. This suggests that dose 2 not only increases the number of RBD-specific Bmem but also the affinity of the Bmem to overcome the point mutations in VoC.

Published
2022

24. CytoBas: Precision component‐resolved diagnostics for allergy using flow cytometric staining of basophils with recombinant allergen tetramers

Author

Bruce D. Wines, Menno C. van Zelm, Pei M. Aui, Jennifer M Rolland, Robyn E O'Hehir, Craig R. M. McKenzie, Nirupama Varese, Philip Mark Hogarth, Francis Thien, and Mark Hew

Subjects
0301 basic medicine, Allergy, Immunology, Basophil, Immunoglobulin E, medicine.disease_cause, Flow cytometry, Allergic sensitization, 03 medical and health sciences, 0302 clinical medicine, Allergen, surface IgE, medicine, Hypersensitivity, Immunology and Allergy, Humans, Sensitization, allergen tetramers, medicine.diagnostic_test, biology, Staining and Labeling, Chemistry, flow cytometry, Allergens, medicine.disease, Molecular biology, component‐resolved diagnostics, Staining, Basophils, Basophil activation, 030104 developmental biology, medicine.anatomical_structure, 030228 respiratory system, biology.protein, Original Article, Basic and Translational Allergy Immunology, ORIGINAL ARTICLES
Abstract

Background Diagnostic tests for allergy rely on detecting allergen‐specific IgE. Component‐resolved diagnostics incorporate multiple defined allergen components to improve the quality of diagnosis and patient care. Objective To develop a new approach for determining sensitization to specific allergen components that utilizes fluorescent protein tetramers for direct staining of IgE on blood basophils by flow cytometry. Methods Recombinant forms of Lol p 1 and Lol p 5 proteins from ryegrass pollen (RGP) and Api m 1 from honeybee venom (BV) were produced, biotinylated, and tetramerized with streptavidin‐fluorochrome conjugates. Blood samples from 50 RGP‐allergic, 41 BV‐allergic, and 26 controls were incubated with fluorescent protein tetramers for flow cytometric evaluation of basophil allergen binding and activation. Results Allergen tetramers bound to and activated basophils from relevant allergic patients but not controls. Direct fluorescence staining of Api m 1 and Lol p 1 tetramers had greater positive predictive values than basophil activation for BV and RGP allergy, respectively, as defined with receiver operator characteristics (ROC) curves. Staining intensities of allergen tetramers correlated with allergen‐specific IgE levels in serum. Inclusion of multiple allergens coupled with distinct fluorochromes in a single‐tube assay enabled rapid detection of sensitization to both Lol p 1 and Lol p 5 in RGP‐allergic patients and discriminated between controls, BV‐allergic, and RGP‐allergic patients. Conclusion Our novel flow cytometric assay, termed CytoBas, enables rapid and reliable detection of clinically relevant allergic sensitization. The intensity of fluorescent allergen tetramer staining of basophils has a high positive predictive value for disease, and the assay can be multiplexed for a component‐resolved and differential diagnostic test for allergy., Fluorescent recombinant allergen tetramers specifically bind to and activate basophils from patients allergic to bee venom (Api m 1) and ryegrass pollen (Lol p 1 and Lol p 5). Staining intensities of recombinant Api m 1 and Lol p 1 tetramers have greater positive predictive values for allergy than basophil activation. A single flow cytometric stain with multiple allergen tetramers can be applied as a rapid component‐resolved and differential diagnostic test for allergy. Abbreviation: Strep, streptavidin

Published
2021

25. COVID-19 pandemic

Author

W. J. Fokkens, Jürgen Schwarze, Cezmi A. Akdis, J Mullol, W. Czarlewski, Claudia Traidl-Hoffmann, Claus Bachert, D. Larenas-Linnemann, Tomas Chivato, M. Gotua, Mateo Bonini, Ludger Klimek, Vincenzo Patella, A. A. Cruz, Stephanie Dramburg, Kari C. Nadeau, H W Fritsch, K. Ohta, Thomas Eiwegger, Robert M. Naclerio, Antti Lauerma, A. Yorgancioglu, Aslı Gelincik, Piotr Kuna, Oliver Pfaar, Carmen Riggioni, Violeta Kvedariene, Markus Ollert, Sinthia Bosnic-Anticevich, V. Cardona, S. Del Giacco, Sanna Toppila-Salmi, Helen A. Brough, Heimo Breiteneder, Valérie Hox, B. Samolinski, Zuzana Diamant, G.W. Canonica, Lihong Zhang, María José Torres, Y. Okamoto, Liam O'Mahony, Radosław Gawlik, Jolanta Walusiak-Skorupa, Sharon Chinthrajah, Winfried Rief, T. Haatela, M. Morais-Almeida, Ioana Agache, Manfred Schedlowski, I Skypala, R. Brehler, D. Y. Wang, João Fonseca, I. J. Ansotegui, Robyn E O'Hehir, Oscar Palomares, Charlotte G. Mortz, J. C. Ivancevich, C. Suppli Ulrik, M. T. Ventura, P M Matricardi, S Untersmayr, Gabrielle L. Onorato, Amir Hamzah Abdul Latiff, Frederico S. Regateiro, Vanitha Sampath, Arũnas Valiulis, Marek Jutel, Luisa Brussino, Pedro Carreiro-Martins, Jean Bousquet, Nikolaos G. Papadopoulos, A. Bedbrook, Torsten Zuberbier, Karin Hoffmann-Sommergruber, Edward F. Knol, Ear, Nose and Throat, AII - Inflammatory diseases, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service d'oto-rhino-laryngologie, Philipps Universität Marburg = Philipps University of Marburg, Allergologie, Stimm und Sprachstörungen [Wiesbaden, Germany], Zentrum für Rhinologie und Allergologie [Wiesbaden, Germany], University of Wrocław [Poland] (UWr), ALL-MED, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Medizinische Universität Wien = Medical University of Vienna, Stanford University, Skane University Hospital [Malmo], Lund University [Lund], Charles University [Prague] (CU), University Medical Center Groningen [Groningen] (UMCG), Univ Toronto, Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Mol Med, Toronto, ON M5G 0A4, Canada, The Hospital for sick children [Toronto] (SickKids), University of Toronto, Amsterdam UMC - Amsterdam University Medical Center, Alfred Health, Victoria University [Melbourne], University College Cork (UCC), Sean N. Parker Center for Allergy and Asthma Research [Stanford], Stanford Medicine, Stanford University-Stanford University, University Clinics of Essen, University of Essen, Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Helmholtz Zentrum München = German Research Center for Environmental Health, University Hospital Augsburg, National University of Singapore (NUS), Beijing Tongren Hospital, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Evelina London Children's Hospital, King‘s College London, CEU-San Pablo University and HM-Hospitals School of Medicine, University of Cagliari, Medical University of Silesia (SUM), Istanbul University, Cliniques Universitaires Saint-Luc [Bruxelles], University Medical Center [Utrecht], Helsinki University Central Hospital, University of Helsinki, Odense University Hospital (OUH), Luxembourg Institute of Health (LIH), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Hospital Sant Joan de Déu [Barcelona], Institut de Recerca Pediàtrica Hospital Sant Joan de Déu [Barcelona, Spain], University of Edinburgh, NHS Foundation Trust [London], The Royal Marsden, Nofer Institute of Occupational Medicine (NIOM), Hospital Quirónsalud Bizkaia [Bilbao], Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], Woolcock Institute of Medical Research [Sydney], The University of Sydney, University of Turin, Mauriziano Umberto I Hospital, Humanitas University [Milan] (Hunimed), Vall d'Hebron University Hospital [Barcelona], Hospital de Dona Estefania, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Federal University of Bahia School of Medicine, Global Alliance Against Chronic Respiratory Diseases (GARD-WHO), Medical Consulting Czarlewski, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, MEDIDA, Lda, David Tvildiani Medical University (DTMU), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Barlicki University Hospital, Vilnius University [Vilnius], Hospital Medica Sur [Mexico City, Mexico], Pantai Hospital [Kuala Lumpur], Hospital CUF Descobertas, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), CIBER de Epidemiología y Salud Pública (CIBERESP), Johns Hopkins University School of Medicine [Baltimore], Fukujuji Hospital, Tokyo National Hospital, Chiba Rosai Hospital, Chiba University Hospital, Royal Manchester Children's Hospital, University of Manchester [Manchester], General Children's Hospital of Athens P & A Kyriakou, 'Santa Maria della Speranza' Hospital, Centro Hospitalar e Universitário [Coimbra], Coimbra Institute for Clinical and Biomedical Research [Coimbra, Portugal] (iCBR - Faculty of Medicine), University of Coimbra [Portugal] (UC), Medical University of Warsaw - Poland, Hvidovre Hospital, University of Copenhagen = Københavns Universitet (UCPH), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Manisa Celal Bayar University, Transilvania University of Brasov, Salvy-Córdoba, Nathalie, Department of Dermatology, Allergology and Venereology, and HUS Inflammation Center

Subjects
0301 basic medicine, viruses, Eaaci Position Paper, Medizin, Cochrane Library, GUIDELINES, FOOD ALLERGY, allergen immunotherapy, allergy clinic, anaphylaxis, asthma, clinical trials, COVID-19, Position Paper, psychological impact, SARS-CoV-2, Allergists, Health Personnel, Humans, Hypersensitivity, Information Technology, Patient Care Team, Triage, SARS‐CoV‐2, DESENSITIZATION, 0302 clinical medicine, MESH: Patient Care Team, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HDE ALER, Pandemic, Health care, Immunology and Allergy, ATOPIC-DERMATITIS, MESH: COVID-19, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, allergen immunotherapy (AIT), virus diseases, DRUG HYPERSENSITIVITY REACTIONS, 3. Good health, INFECTIONS, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Triage, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Allergen immunotherapy, medicine.medical_specialty, MESH: Information Technology, MESH: Hypersensitivity, Immunology, education, MEDLINE, DIAGNOSIS, psychological COVID, 03 medical and health sciences, MESH: Allergists, COVID‐19, medicine, MESH: SARS-CoV-2, ddc:610, RHINOSINUSITIS, MESH: Humans, business.industry, Clinical trial, Coronavirus, EXACERBATIONS, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, 3121 General medicine, internal medicine and other clinical medicine, Position paper, MESH: Health Personnel, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

BackgroundThe Coronavirus disease 2019 (COVID‐19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.MethodThe scientific information on COVID‐19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet.ResultsBased on diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.ConclusionsThis international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID‐19 pandemic.

Published
2021

27. Thunderstorm asthma: an overview of mechanisms and management strategies

Author

Jo A Douglass, Janet M. Davies, Francis Thien, Robyn E O'Hehir, and Mark Hew

Subjects
Risk, Climate Change, Immunology, Patient Education as Topic, Environmental health, Asthma mortality, Humans, Immunology and Allergy, Medicine, Weather, Asthma, Air Pollutants, Childhood asthma, Individual susceptibility, biology, business.industry, Outbreak, Allergic asthma, Allergens, medicine.disease, Alternaria, biology.organism_classification, Desensitization, Immunologic, Gene-Environment Interaction, Public Health, business, Forecasting
Abstract

Epidemic thunderstorm asthma (ETSA) is due to a complex interaction of environmental and individual susceptibility factors, with outbreaks reported globally over the last four decades. Australia has been particularly susceptible with nearly half of episodes reported internationally, culminating in the catastrophic Melbourne 2016 event.Reported ETSA episodes are reviewed for common environmental and meteorological risk factors. Allergen aerobiology interaction with thunderstorm activity and rapid weather condition changes is examined. Assessment of the clinical and immunological data highlights risk factors for ETSA presentation, hospital admission, and intensive care admission. Risk factors associated with ETSA deaths are evaluated. Public health strategies, as well as pharmacological and immunological management approaches to reduce individual susceptibility and prevent ETSA are discussed.Improved understanding of the specific meteorological factors predisposing to the greatest risk of ETSA to improve forecasting is required. Better monitoring of aeroallergen levels in areas of greatest geographic risk, with further research into allergen aerobiology underpinning mechanisms of allergen exposure is needed. The role of climate change in increasing the risk of ETSA outbreaks requires further research. Public awareness and education are required to reduce exposure, and to improve uptake of pharmacological and immunological risk reduction and preventive strategies.

Published
2020

28. Beyond monogenetic rare variants: tackling the low rate of genetic diagnoses in predominantly antibody deficiency

Author

Emily S.J. Edwards, Julian J. Bosco, Samar Ojaimi, Robyn E O'Hehir, and Menno C. van Zelm

Subjects
Genetic Markers, 0301 basic medicine, medicine.medical_treatment, Immunology, Genomics, Review Article, Disease, Bioinformatics, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Humans, Immunology and Allergy, Medicine, Genetic Predisposition to Disease, business.industry, Genetic heterogeneity, Genetic Variation, medicine.disease, Common Variable Immunodeficiency, 030104 developmental biology, Infectious Diseases, Disease Presentation, Primary immunodeficiency, Personalized medicine, Immune disorder, business, 030215 immunology
Abstract

Predominantly antibody deficiency (PAD) is the most prevalent form of primary immunodeficiency, and is characterized by broad clinical, immunological and genetic heterogeneity. Utilizing the current gold standard of whole exome sequencing for diagnosis, pathogenic gene variants are only identified in less than 20% of patients. While elucidation of the causal genes underlying PAD has provided many insights into the cellular and molecular mechanisms underpinning disease pathogenesis, many other genes may remain as yet undefined to enable definitive diagnosis, prognostic monitoring and targeted therapy of patients. Considering that many patients display a relatively late onset of disease presentation in their 2(nd) or 3(rd) decade of life, it is questionable whether a single genetic lesion underlies disease in all patients. Potentially, combined effects of other gene variants and/or non-genetic factors, including specific infections can drive disease presentation. In this review, we define (1) the clinical and immunological variability of PAD, (2) consider how genetic defects identified in PAD have given insight into B-cell immunobiology, (3) address recent technological advances in genomics and the challenges associated with identifying causal variants, and (4) discuss how functional validation of variants of unknown significance could potentially be translated into increased diagnostic rates, improved prognostic monitoring and personalized medicine for PAD patients. A multidisciplinary approach will be the key to curtailing the early mortality and high morbidity rates in this immune disorder.

Published
2020

29. Paradoxical Vocal Fold Motion in Difficult Asthma Is Associated with Dysfunctional Breathing and Preserved Lung Function

Author

Joy Lee, Eli Dabscheck, Fiona Hore-Lacy, Janet Bondarenko, Mark Hew, Michael J. Abramson, Naghmeh Radhakrishna, Eve Denton, Tunn Ren Tay, Ryan Hoy, and Robyn E O'Hehir

Subjects
Larynx, medicine.medical_specialty, Laryngoscopy, Provocation test, Vocal Cords, Hospital Anxiety and Depression Scale, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Vocal cord dysfunction, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, Lung, Asthma, medicine.diagnostic_test, business.industry, Respiration, Odds ratio, medicine.disease, medicine.anatomical_structure, Vocal Cord Dysfunction, 030228 respiratory system, Cardiology, business
Abstract

Many patients with difficult asthma also have coexisting vocal cord dysfunction (VCD), evident by paradoxical vocal fold motion (PVFM) on laryngoscopy.Among patients with difficult asthma, we sought to identify clinical features associated with laryngoscopy-diagnosed PVFM.Consecutive patients with "difficult asthma" referred by respiratory specialists underwent systematic assessment in this observational study. Those with a high clinical suspicion for VCD were referred for laryngoscopy, either at rest or after mannitol provocation. Statistical analyses were performed to identify clinical factors associated with PVFM, and a multivariate logistic regression model was fitted to control for confounders.Of 169 patients with difficult asthma, 63 (37.3%) had a high clinical probability of VCD. Of 42 who underwent laryngoscopy, 32 had PVFM confirmed. Patients with PVFM more likely had preserved lung function (prebronchodilator forced expiratory ratio 74% ± 11 vs 62% ± 16, P.001); physiotherapist-confirmed dysfunctional breathing (odds ratio [OR] = 5.52, 95% confidence interval [CI]: 2.4-12.7, P.001), gastro-oesophageal reflux (OR = 2.6, 95% CI: 1.16-5.8, P = .02), and a lower peripheral eosinophil count (0.09 vs 0.23, P = .004). On multivariate logistic regression, independent predictors for PVFM were dysfunctional breathing (OR = 4.93, 95% CI: 2-12, P.001) and preserved lung function (OR = 1.07, 95% CI: 1.028-1.106, P.001).Among specialist-referred patients with difficult asthma, VCD pathogenesis may overlap with dysfunctional breathing but is not associated with severe airflow obstruction. Dysfunctional breathing and preserved lung function may serve as clinical clues for the presence of VCD.

Published
2020

30. Epidemic thunderstorm asthma susceptibility from sensitization to ryegrass ( Lolium perenne ) pollen and major allergen Lol p 5

Author

P.M. Hogarth, Nirupama Varese, Mark Hew, Craig R. M. McKenzie, Heather Aumann, Jennifer M. Rolland, Menno C. van Zelm, Pei M. Aui, Robyn E O'Hehir, Joy Lee, and Bruce D. Wines

Subjects
LOLIUM PERENNE POLLEN, Allergy, Immunology, medicine.disease_cause, Allergen, Pollen, Botany, Lolium, medicine, Humans, Immunology and Allergy, Epidemics, Letters to the Editor, Letter to the Editor, Sensitization, Plant Proteins, Asthma, biology, business.industry, Allergens, Antigens, Plant, medicine.disease, biology.organism_classification, medicine.anatomical_structure, Rye grass pollen, business
Published
2020

31. Induction of IgG2 and IgG4 B-cell memory following sublingual immunotherapy for ryegrass pollen allergy

Author

Mark Hew, Jennifer M. Rolland, Menno C. van Zelm, Pei M. Aui, Nirupama Varese, Craig R. M. McKenzie, Amy T C M Bakx, Jorn J Heeringa, Robyn E O'Hehir, and Immunology

Subjects
0301 basic medicine, Allergy, Atopic Rhinitis, medicine.medical_treatment, Immunology, immunotherapy and tolerance induction, Immunoglobulin E, Peripheral blood mononuclear cell, 03 medical and health sciences, 0302 clinical medicine, Immune system, Hypersensitivity, Lolium, medicine, Humans, Immunology and Allergy, B cell, Rhinitis, B cells, B-Lymphocytes, Sublingual Immunotherapy, biology, business.industry, flow cytometry, Rhinitis, Allergic, Seasonal, Immunotherapy, Allergens, medicine.disease, Slit, 030104 developmental biology, medicine.anatomical_structure, 030228 respiratory system, Desensitization, Immunologic, Immunoglobulin G, Leukocytes, Mononuclear, biology.protein, Pollen, Original Article, Basic and Translational Allergy Immunology, IgE, ORIGINAL ARTICLES, business
Abstract

Background While treatment for atopic rhinitis is aimed mostly to relieve symptoms, only allergen‐specific immunotherapy (AIT) is targeted to modify the natural history of allergic diseases. This results in sustained clinical tolerance, even when treatment has stopped. The immunomodulatory effects of AIT are attributed mainly to increased regulatory T‐cell function and increased allergen‐specific IgG4, yet little is known about the effect on the memory B‐cell compartment. Objective We aimed to examine the effects of AIT on the IgE‐ and IgG subclass‐expressing memory B cells. Methods We recruited 29 patients with atopic seasonal rhinoconjunctivitis and performed a longitudinal analysis of the peripheral immune compartment before, during, and after sublingual immunotherapy (SLIT) for allergy to temperate grass pollen, predominantly to ryegrass pollen (RGP; Lolium perenne). Using flow cytometry on peripheral blood mononuclear cells and serum immunoassays, we analyzed the effects of a 4 months preseasonal treatment regimen comprising two or three courses in consecutive years on circulating IgE+ and IgG+ memory B cells and allergen‐specific Ig levels. Results SLIT increased RGP‐specific serum IgG2 and IgG4, as well as the frequencies of IgG2 + and IgG4 + memory B cells, whereas no effect was observed on the IgE+ memory B‐cell compartment. Furthermore, SLIT enhanced proportions of regulatory T cells specific to RGP. These changes were associated with clinical improvement. Conclusion Our data provide evidence for immunological effects of SLIT on B‐cell memory. Skewing responses toward IgG2 and IgG4 subclasses might be a mechanism to suppress IgE‐mediated allergic responses., This study examines the effect of ryegrass pollen AIT on B‐cell responses in a population of 29 patients with allergic rhinitis. Successful immunotherapy for ryegrass pollen allergy increases allergen‐specific IgG2 and IgG4 serum levels, and proportions of IgG2‐ and IgG4‐expressing memory B cells. Skewing toward the anti‐inflammatory IgG2 and IgG4 subclasses might be a mechanism to suppress IgE‐mediated allergic responses.

Published
2020

32. Peanut oral immunotherapy: current trends in clinical trials

Author

Simone Reinwald, Jennifer M Rolland, Robyn E O’Hehir, and Menno C van Zelm

Subjects
General Medicine
Abstract

Immunotherapy for allergy has been practiced for over 100 years. Low-dose repeated exposure to specific allergen extracts over several months to years can successfully induce clinical tolerance in patients with allergy to insect venoms, pollen, house dust mite, and domestic animals. Different regimens and routes for immunotherapy include subcutaneous, sublingual, oral, and intralymphatic. Food allergies have been difficult to treat in this way due to high anaphylactic potential and only recently the first immunotherapy for peanut allergy has received regulatory approval. Several clinical trials have indicated high efficacy in desensitisation of peanut-allergic individuals using oral immunotherapy, which allows for safer administration of relatively high allergen concentrations. Still, the risk of adverse events including serious allergic reactions and high anxiety levels for patients remains, demonstrating the need for further optimisation of treatment protocols. Here we discuss the design and outcomes of recent clinical trials with traditional oral immunotherapy, and consider alternative protocols and formulations for safer and more effective oral treatment strategies for peanut allergy.

Published
2022

33. Preface

Author

Robyn E. O'Hehir, Stephen T. Holgate, Aziz Sheikh, and Gurjit K. Khurana Hershey

Published
2022

34. Contributors

Author

Cezmi A. Akdis, Mübeccel Akdis, Fuad M. Baroody, Mark Boguniewicz, Simon G.A. Brown, A. Wesley Burks, Anca-Mirela Chiriac, Jonathan Corren, Adnan Custovic, Pascal Demoly, Luz Fonacier, David B.K. Golden, Clive E.H. Grattan, Oliver V. Hausmann, Gurjit K. Khurana Hershey, Stephen T. Holgate, Lukas Joerg, Catherine Lemière, Donald Y.M. Leung, Tesfaye B. Mersha, Anna Nowak-Węgrzyn, Robyn E. O'Hehir, Clive Robinson, Umit Sahiner, Sarbjit S. Saini, Hugh A. Sampson, Aziz Sheikh, Michael G. Sherenian, Helen E. Smith, Geoffrey A. Stewart, Hille Suojalehto, and Paul J. Turner

Published
2022

35. Coordinated IgG2 and IgE responses as a marker of allergen immunotherapy efficacy

Author

Thierry Batard, Laurent Mascarell, Menno C. van Zelm, Véronique Bordas-Le Floch, Nirupama Varese, Walter Canonica, Nathalie Berjont, and Robyn E O'Hehir

Subjects
Allergen immunotherapy, High responder, medicine.medical_treatment, Immunology, Immunoglobulin E, Immune system, Antigen, Grass pollen, parasitic diseases, medicine, Immunology and Allergy, Animals, Humans, Antigens, Dermatophagoides, House dust mite, Sublingual Immunotherapy, biology, business.industry, Pyroglyphidae, Immunotherapy, Allergens, biology.organism_classification, Treatment Outcome, Desensitization, Immunologic, Immunoglobulin G, biology.protein, business, Biomarkers, Tablets
Abstract

Background IgG2 responses are associated with repeated antigen exposure and display highly mutated variable domains. A recent study highlighted a role of IgG2+ memory B cells and allergen-specific IgG2 levels after a 3rd consecutive pre-seasonal sublingual allergen immunotherapy (AIT) with grass pollen tablet. Herein, we aim to explore changes in allergen-specific IgG2 in individuals undergoing house dust mite immunotherapy (HDM-AIT) and explore whether the interrelationship with other humoral responses (i.e., IgG4 and IgE) may discriminate between high and low responders. Methods Levels of serum Dermatophagoides pteronyssinus and Dermatophagoides farinae-specific IgG2, IgG4, and IgE antibodies were measured by ELISA or ImmunoCap in a sub-group of individuals enrolled in a randomized, double-blind, placebo-controlled, sublingual AIT study evaluating the safety and efficacy of a 300 IR HDM tablet. Results After 1-year sublingual AIT, HDM-specific serum IgG2 responses increase mostly in high versus low responders and are distinctive according to the clinical benefit. Higher correlation between HDM-specific IgG2, IgE, and/or IgG4 responses is seen in subjects benefiting the most from HDM-AIT as indicated by changes in Average Total Combined Scores. More strikingly, statistically significant correlation between HDM-specific IgG2 and IgE responses is only observed in individuals stratified as high responders. Conclusions We provide evidence for coordinated serum immune responses upon AIT in HDM-allergic subjects exhibiting high clinical benefit when compared with low responders. Assessing HDM-specific IgE, IgG2, and IgG4 in serum could be used as follow-up combined markers to support decision as to AIT continuation and/or adaptation.

Published
2021

36. Factors Associated with Dysfunctional Breathing in Patients with Difficult to Treat Asthma

Author

Eli Dabscheck, Robyn E O'Hehir, Eve Denton, Mark Hew, Janet Bondarenko, TunnRen Tay, Joy Lee, Naghmeh Radhakrishna, Fiona Hore-Lacy, Ryan Hoy, and Catherine Martin

Subjects
Adult, Male, medicine.medical_specialty, Exacerbation, Anxiety, Hospital Anxiety and Depression Scale, Severity of Illness Index, Risk Factors, Surveys and Questionnaires, Internal medicine, Severity of illness, Odds Ratio, medicine, Vocal cord dysfunction, Humans, Immunology and Allergy, Aged, Asthma, Depression, business.industry, Respiration, Sleep apnea, Odds ratio, Middle Aged, Respiration Disorders, medicine.disease, Female, Sino-Nasal Outcome Test, medicine.symptom, business
Abstract

Background Understanding of dysfunctional breathing in patients with difficult asthma who remain symptomatic despite maximal inhaler therapy is limited. Objective We characterized the pattern of dysfunctional breathing in patients with difficult asthma and identified possible contributory factors. Methods Dysfunctional breathing was identified in patients with difficult asthma using the Nijmegen Questionnaire (score >23). Demographic characteristics, asthma variables, and comorbidities were assessed. Multivariate logistic regression was performed for dysfunctional breathing, adjusted for age, sex, body mass index, and airflow obstruction. Results Of 157 patients with difficult asthma, 73 (47%) had dysfunctional breathing. Compared with patients without dysfunctional breathing, those with dysfunctional breathing experienced poorer asthma status (symptom control, quality of life, and exacerbation rates) and greater unemployment. In addition, more frequently they had elevated sino-nasal outcome test scores, anxiety, depression, sleep apnea, and gastroesophageal reflux. On multivariate analysis, anxiety (odds ratio [OR], 3.26; 95% CI, 1.18-9.01; P = .02), depression (OR, 2.8; 95% CI, 1.14-6.9; P = .03), and 22-item sino-nasal outcome test score (OR, 1.03; 95% CI, 1.003-1.05; P = .03) were independent risk factors for dysfunctional breathing. Conclusions Dysfunctional breathing is common in difficult asthma and associated with worse asthma status and unemployment. The independent association with psychological disorders and nasal obstruction highlight an important interaction between comorbid treatable traits in difficult asthma.

Published
2019

37. Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA

Author

Jere Reijula, De Yun Wang, Ralph Mösges, Tomohisa Iinuma, Jean Luc Fauquert, Nelson Rosario, Yehia El-Gamal, René Maximiliano Gómez, Tari Haahtela, Vincenzo Patella, Lorenzo Cecchi, Petr Panzner, Yoshitaka Okamoto, Oliver Pfaar, Luis Caraballo, Paulo Augusto Moreira Camargos, Filip Raciborski, Florin Mihaltan, Ken Ohta, Brian J. Lipworth, Kimi Okubo, Juan Carlos Ivancevich, Fulvio Braido, Ioana Agache, Frederico S. Regateiro, Neven Miculinic, Tuula Vasankari, R. Emuzyte, Arunas Valiulis, Yousser Mohammad, Torsten Zuberbier, Osman M. Yusuf, Ewa Jassem, Cezmi A. Akdis, Jean Bousquet, Alessandro Fiocchi, Jan Hagemann, Claus Bachert, Davor Plavec, K. S. Bennoor, Marek Jutel, Désirée Larenas-Linnemann, Stephen Montefort, Stefano Del Giacco, Przemyslaw Kardas, Erkka Valovirta, Mark S. Dykewicz, Antonio Valero, Wienczyslawa Czarlewski, Thomas B. Casale, Gabrielle L. Onorato, Omer Kalayci, Ludger Klimek, Joaquin Sastre, João Fonseca, Siân Williams, Karl Christian Bergmann, Marek Niedoszytko, Bilun Gemicioglu, Mario E. Zernotti, Musa Khaitov, H. Neffen, Robert M. Naclerio, Joaquim Mullol, Ana Pereira, Piotr Kuna, Michael Makris, Maria Teresa Ventura, Ioanna Tsiligianni, Dirceu Solé, Arzu Yorgancioglu, Charlotte Suppli-Ulrik, M. Gotua, Emmanuel P. Prokopakis, Dana Wallace, Jorge Maspero, Wytske Fokkens, Eckard Hamelmann, Antonino Romano, Dejan Dokic, Todor A. Popov, Violeta Kvedariene, Derek K. Chu, Anna Bedbrook, Dermot Ryan, Motohiro Ebisawa, Tomas Chivato, Giovanni Passalacqua, Menachem Rottem, Mário Morais-Almeida, Victoria Cardona, Bolesław Samoliński, Cristiana Stellato, Nikolaos G. Papadopoulos, Milan Sova, Jaime Correia-de-Sousa, Sietze Reitsma, Cemal Cingi, Francesca Puggioni, Robyn E O'Hehir, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, HUS Internal Medicine and Rehabilitation, Department of Public Health, Clinicum, Keuhkosairauksien yksikkö, Helsinki University Hospital Area, University of Helsinki, University Medical Center of the Johannes Gutenberg-University Mainz, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Wrocław [Poland] (UWr), Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Transilvania University of Brasov, Humboldt University Of Berlin, Medical Consulting Czarlewski, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), MASK-air, Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], National Institute of Diseases of the Chest and Hospital (NIDCH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Ospedale Policlinico San Martino [Genoa], Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), University of Cartagena, Foundation for the Development of Medical and Biological Sciences (FUNDEMEB), Vall d'Hebron University Hospital [Barcelona], Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], University of South Florida [Tampa] (USF), Azienda Usl Toscana centro [Firenze], CEU-San Pablo University and HM-Hospitals School of Medicine, McMaster University [Hamilton, Ontario], Eskisehir Osmangazi University, Universidade do Minho = University of Minho [Braga], Life and Health Sciences Research Institute [Braga] (ICVS), University of Minho [Braga], The International Primary Care Respiratory Group (IPCRG), Università degli Studi di Cagliari = University of Cagliari (UniCa), Sts. Cyril and Methodius University, Saint Louis University School of Medicine [St Louis], Sagamihara National Hospital [Kanagawa, Japan], Ain Shams University (ASU), Vilnius University [Vilnius], Service de Pédiatrie Générale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Bambino Gesù Children’s Hospital [Rome, Italy], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Center of Research in Health Technologies and Information Systems (CINTESIS), Universidade do Porto = University of Porto, CUF Porto Hospital, Cerrahpasa Faculty of Medicine, Istanbul University, ALAS Medical Institute, Center for Allergy and Immunology Research [Tbilisi], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Universität Bielefeld = Bielefeld University, Chiba University Hospital, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Medical University of Gdańsk, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Medical University of Łódź (MUL), Federal Medicobiological Agency [Moscow, Russian Federation], Hospital Medica Sur [Mexico City, Mexico], Ninewells Hospital and Medical School [Dundee], University General Hospital ' Attikon ' [Athens, Greece], Argentine Association of Allergy and Immunology, Marius Nasta Institute of Pneumology, Tishreen University, Université de Damas = Damascus University, University of Malta [Malta], Hospital CUF Descobertas, Clinical Research International Ltd [Hamburg, Germany] (CRI), Johns Hopkins University School of Medicine [Baltimore], Nemours/Alfred I. du Pont Hospital for Children, Monash University [Melbourne], Tokyo National Hospital, Nippon Medical School [Tokyo, Japon], Medicine Charles University and General Faculty Hospital in Prague, Royal Manchester Children's Hospital, University of Manchester [Manchester], Università degli studi di Genova = University of Genoa (UniGe), 'Santa Maria della Speranza' Hospital, Philipps Universität Marburg = Philipps University of Marburg, J.J. Strossmayer University of Osijek, Children’s Hospital Srebrnjak [Zagreb, Croatia], St. Ivan Rilski University Hospital, University of Crete [Heraklion] (UOC), IRCCS Humanitas [Rozzano, Italy], Medical University of Warsaw - Poland, Centro Hospitalar e Universitário [Coimbra], Amsterdam UMC - Amsterdam University Medical Center, Istituto di Ricovero e Cura a Carattere Scientifico [Troina, Italy] (IRCCS), Oasi Maria Santissima Srl [Troina, Italy], Clinica G.B. Morgagni (Fondazione Mediterranea), Pontifical Catholic University of Paraná (PUCPR), Pontifícia Universidade Católica do Paraná (PUCPR), Ha’Emek Medical Center [Afula, Israel], Pediatric Endocrine Institute [Afula, Israel], Usher Institute of Population Health Sciences and Informatics [Edinburgh, U.K.], University of Edinburgh, Federal University of Sao Paulo (Unifesp), University Hospital Olomouc [Czech Republic], University of Salerno (UNISA), Copenhagen University Hospital, Universitat de Barcelona (UB), European Academy of Paediatrics (EAP/UEMS-SP), University of Turku, Suomen Terveystalo Allergy Clinic, Finnish Lung Health Association, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Nova Southeastern University (NSU), Yong Loo Lin School of Medicine [Singapore], Department of Biology, Faculty of Sciences & Liberal Arts, Celal Bayar University, Manisa Celal Bayar University, The Allergy & Asthma Institute, Pakistan (IPCRG), Universidad Nacional de Villa María, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Allergiezentrum Wiesbaden, Salvy-Córdoba, Nathalie, Ear, Nose and Throat, and AII - Inflammatory diseases

Subjects
0301 basic medicine, Allergy, MESH: Asthma, Common Cold, allergic rhinitis, common cold, cough, COVID-19, smell, Consensus, Humans, SARS-CoV-2, Asthma, Rhinitis, Allergic, Disease, Care, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, MESH: COVID-19, Rhinitis, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Common cold, 3. Good health, MESH: Rhinitis, Allergic, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Original Article, medicine.symptom, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Immunology, Signs and symptoms, Asymptomatic, 03 medical and health sciences, Allergic, COVID‐19, Internal medicine, medicine, MESH: SARS-CoV-2, MESH: Consensus, MESH: Humans, business.industry, Rhinitis, Sinusitis, and Upper Airway Disease, CARE, medicine.disease, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ORIGINAL ARTICLES, Airway, business, MESH: Common Cold
Abstract

Background Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. Methods A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. Results Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). Conclusions This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.

Published
2021

38. Vaccines and Allergic reactions: the past, the current COVID-19 pandemic, and future perspectives

Author

Menno C. van Zelm, Wytske Fokkens, Oscar Palomares, Sharon Chinthrajah, Mihir Shah, Liam O'Mahony, Oliver Pfaar, Katie Fast, Grace Rabinowitz, Robyn E O'Hehir, Surabhi Jain, Ioana Agache, Domingo Barber Hernández, Ronald L. Rabin, De Yun Wang, Tomas Chivato, Kari C. Nadeau, María José Torres, Milena Sokolowska, William Collins, Thomas Eiwegger, Carmen Riggioni, Zuzana Diamant, Markus Ollert, Luo Zhang, Vanitha Sampath, Claudia Traidl-Hoffmann, Cezmi A. Akdis, Milos Jesenak, Mohamed H. Shamji, and Stefan Vieths

Subjects
Vaccination, Safety profile, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Vaccine manufacturing, Infectious disease (medical specialty), business.industry, Public health, Incidence (epidemiology), Pandemic, medicine, Intensive care medicine, business
Abstract

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.

Published
2021

39. Evaluation of Diagnosis and Management of Omega-5-Gliadin Allergy: A Retrospective Survey

Author

Celia Zubrinich, Mark Hew, Robert Puy, and Robyn E O'Hehir

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pediatrics, Allergy, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Food allergy, Epidemiology, medicine, Journal of Asthma and Allergy, anaphylaxis, Immunology and Allergy, 0601 history and archaeology, FDEIA, Asthma, Original Research, WDEIA, chemistry.chemical_classification, wheat-dependent exercise-induced anaphylaxis, food allergy, 060102 archaeology, business.industry, 06 humanities and the arts, medicine.disease, Gluten, wheat allergy, food-dependent exercise-induced anaphylaxis, 030228 respiratory system, chemistry, business, omega-5-gliadin allergy, Wheat allergy, Anaphylaxis
Abstract

Celia Zubrinich,1,2 Robert Puy,1,3 Robyn O’Hehir,1,3 Mark Hew1,2 1Allergy, Asthma & Clinical Immunology, Alfred Health, Melbourne, Victoria, Australia; 2School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia; 3Allergy, Immunology and Respiratory Medicine, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaCorrespondence: Celia Zubrinich Email c.zubrinich@alfred.org.auBackground: Allergy to the omega-5-gliadin component of gluten (O-5-G allergy) often manifests when wheat ingestion is followed by a co-factor, usually exercise. There is no established best approach to management.Objective: We sought to identify the beneficial effects, firstly of establishing a firm diagnosis, and secondly of stringent management, either by avoiding gluten ingestion altogether or separating it temporally from exercise by at least 4 hours. We also determined how frequently patients adhered to their physicians’ clinical recommendations.Methods: We undertook a survey of individuals diagnosed with O-5-G allergy at our institution over 8 years, who had a consistent clinical history and confirmatory laboratory evidence.Results: Of 80 eligible individuals, 43 responded (54%). Symptoms began in adulthood for all bar one, and concurrent asthma and eczema was uncommon (9% prevalence, respectively). Median time to diagnosis was 2 years. Achieving a diagnosis reduced the rate of reactions (0.35 per month vs 1.085 reactions per month, p=0.029). Many patients (10/43) did not adhere to the recommended stringent approach, to either avoid wheat/gluten or separate food and exercise by 4 hours. However, those adopting a stringent approach had a substantially lower risk of recurrent allergic reaction (0.22 per month vs 0.74 per month, p=0.004).Conclusion: The epidemiology of O-5-G allergy implies pathogenic mechanisms potentially distinct from those of childhood-onset food allergy. Accurate diagnosis improves the clinical trajectory, primarily through the adoption of a stringent management approach.Keywords: omega-5-gliadin allergy, wheat allergy, food allergy, anaphylaxis, wheat-dependent exercise-induced anaphylaxis, WDEIA, food-dependent exercise-induced anaphylaxis, FDEIA

Published
2021

40. ARIA-EAACI care pathways for allergen immunotherapy in respiratory allergy

Author

Jean Bousquet, Oliver Pfaar, Ioana Agache, Anna Bedbrook, Cezmi A. Akdis, Giorgio Walter Canonica, Tomas Chivato, Mona Al-Ahmad, Amir H. Abdul Latiff, Ignacio J. Ansotegui, Claus Bachert, Abdullah Baharuddin, Karl C. Bergmann, Carsten Bindslev-Jensen, Leif Bjermer, Matteo Bonini, Sinthia Bosnic-Anticevich, Isabelle Bosse, Helen A. Brough, Luisa Brussino, Moises A. Calderon, Luis Caraballo, Victoria Cardona, Pedro Carreiro-Martins, Tomas Casale, Lorenzo Cecchi, Alfonso M. Cepeda Sarabia, Ekaterine Chkhartishvili, Derek K. Chu, Ieva Cirule, Alvaro A. Cruz, Wienczyslawa Czarlewski, Stefano del Giacco, Pascal M. Demoly, Philippe Devillier, Dejan Dokic, Stephen R. Durham, Motohiro Ebisawa, Yehia El-Gamal, Regina Emuzyte, Amiran Gamkrelidze, Jean Luc Fauquert, Alessandro Fiocchi, Wytske J. Fokkens, Joao A. Fonseca, Jean François Fontaine, Radoslaw Gawlik, Asli Gelincik, Bilun Gemicioğlu, Jose E. Gereda, R (Roy) Gerth van Wijk, René Maximiliano Gomez, Maia Gotua, Ineta Grisle, Maria Antonieta Guzmán, Tari Haahtela, Susanne Halken, Enrico Heffler, Karin Hoffmann-Sommergruber, Elham Hossny, Martin Hrubiško, Carla Irani, Juan Carlos Ivancevich, Zhanat Ispayeva, Kaja Julge, Igor Kaidashev, Omer Kalayci, Musa Khaitov, Ludger Klimek, Edward Knol, Marek L. Kowalski, Helga Kraxner, Inger Kull, Piotr Kuna, Violeta Kvedariene, Vicky Kritikos, Antti Lauerma, Susanne Lau, Daniel Laune, Michael Levin, Désirée E. Larenas-Linnemann, Karin C. Lodrup Carlsen, Carlo Lombardi, Olga M. Lourenço, Bassam Mahboub, Hans Jørgen Malling, Patrick Manning, Gailen D. Marshall, Erik Melén, Eli O. Meltzer, Neven Miculinic, Branislava Milenkovic, Mostafa Moin, Steve Montefort, Mario Morais-Almeida, Charlotte G. Mortz, Ralph Mösges, Joaquim Mullol, Leyla Namazova-Baranova, Hugo Neffen, Kristoff Nekam, Marek Niedoszytko, Mikaëla Odemyr, Robyn E. O'Hehir, Markus Ollert, Liam O'Mahony, Ken Ohta, Yoshitaka Okamoto, Kimi Okubo, Giovanni B. Pajno, Oscar Palomares, Susanna Palkonen, Peter Panzner, Nikolaos G Papadopoulos, Hae Sim Park, Gianni Passalacqua, Vincenzo Patella, Ruby Pawankar, Nhân Pham-Thi, Davor Plavec, Todor A. Popov, Marysia Recto, Frederico S. Regateiro, Carmen Riggioni, Graham Roberts, Monica Rodriguez-Gonzales, Nelson A. Rosário Filho, Menachem Rottem, Philip W. Rouadi, Dermot Ryan, Boleslaw Samolinski, Mario M. Sanchez-Borges, Faradiba Sarquis Serpa, Joaquin Sastre, Glenis K. Scadding, Mohamed Shamji, Peter Schmid-Grendelmeier, Holger J. Schünemann, A (Aziz) Sheikh, Nicola Scichilone, Juan Carlos Sisul, Mikhail Sofiev, Dirceu Solé, Talant Sooronbaev, Manuel Soto-Martinez, Manuel Soto-Quiros, Milan Sova, Jürgen Schwarze, Isabel Skypala, Charlotte Suppli Ulrik, Luis Taborda-Barata, Ana Todo-Bom, Maria J. Torres, Marylin Valentin-Rostan, Peter Valentin Tomazic, Antonio A. Valero, Sanna Toppila-Salmi, Ioanna Tsiligianni, Eva Untersmayr, Marilyn Urrutia-Pereira, Arunas Valiulis, Erkka Valovirta, Olivier Vandenplas, Maria Teresa Ventura, Pakit Vichyanond, Martin Wagenmann, Dana Wallace, Jolanta Walusiak-Skorupa, De Yun Wang, Susan Waserman, Gary Wong, Arzu Yorgancioglu, Osman M. Yusuf, Mario E. Zernotti, Luo Zhang, Mihaela Zidarn, Torsten Zuberbier, Marek Jutel, Jean Bousquet, Oliver Pfaar, Ioana Agache, Anna Bedbrook, Cezmi A. Akdis, Giorgio Walter Canonica, Tomas Chivato, Mona Al-Ahmad, Amir H. Abdul Latiff, Ignacio J. Ansotegui, Claus Bachert, Abdullah Baharuddin, Karl C. Bergmann, Carsten Bindslev-Jensen, Leif Bjermer, Matteo Bonini, Sinthia Bosnic-Anticevich, Isabelle Bosse, Helen A. Brough, Luisa Brussino, Moises A. Calderon, Luis Caraballo, Victoria Cardona, Pedro Carreiro-Martins, Tomas Casale, Lorenzo Cecchi, Alfonso M. Cepeda Sarabia, Ekaterine Chkhartishvili, Derek K. Chu, Ieva Cirule, Alvaro A. Cruz, Wienczyslawa Czarlewski, Stefano del Giacco, Pascal M. Demoly, Philippe Devillier, Dejan Dokic, Stephen R. Durham, Motohiro Ebisawa, Yehia El-Gamal, Regina Emuzyte, Amiran Gamkrelidze, Jean Luc Fauquert, Alessandro Fiocchi, Wytske J. Fokkens, Joao A. Fonseca, Jean François Fontaine, Radoslaw Gawlik, Asli Gelincik, Bilun Gemicioğlu, Jose E. Gereda, R (Roy) Gerth van Wijk, René Maximiliano Gomez, Maia Gotua, Ineta Grisle, Maria Antonieta Guzmán, Tari Haahtela, Susanne Halken, Enrico Heffler, Karin Hoffmann-Sommergruber, Elham Hossny, Martin Hrubiško, Carla Irani, Juan Carlos Ivancevich, Zhanat Ispayeva, Kaja Julge, Igor Kaidashev, Omer Kalayci, Musa Khaitov, Ludger Klimek, Edward Knol, Marek L. Kowalski, Helga Kraxner, Inger Kull, Piotr Kuna, Violeta Kvedariene, Vicky Kritikos, Antti Lauerma, Susanne Lau, Daniel Laune, Michael Levin, Désirée E. Larenas-Linnemann, Karin C. Lodrup Carlsen, Carlo Lombardi, Olga M. Lourenço, Bassam Mahboub, Hans Jørgen Malling, Patrick Manning, Gailen D. Marshall, Erik Melén, Eli O. Meltzer, Neven Miculinic, Branislava Milenkovic, Mostafa Moin, Steve Montefort, Mario Morais-Almeida, Charlotte G. Mortz, Ralph Mösges, Joaquim Mullol, Leyla Namazova-Baranova, Hugo Neffen, Kristoff Nekam, Marek Niedoszytko, Mikaëla Odemyr, Robyn E. O'Hehir, Markus Ollert, Liam O'Mahony, Ken Ohta, Yoshitaka Okamoto, Kimi Okubo, Giovanni B. Pajno, Oscar Palomares, Susanna Palkonen, Peter Panzner, Nikolaos G Papadopoulos, Hae Sim Park, Gianni Passalacqua, Vincenzo Patella, Ruby Pawankar, Nhân Pham-Thi, Davor Plavec, Todor A. Popov, Marysia Recto, Frederico S. Regateiro, Carmen Riggioni, Graham Roberts, Monica Rodriguez-Gonzales, Nelson A. Rosário Filho, Menachem Rottem, Philip W. Rouadi, Dermot Ryan, Boleslaw Samolinski, Mario M. Sanchez-Borges, Faradiba Sarquis Serpa, Joaquin Sastre, Glenis K. Scadding, Mohamed Shamji, Peter Schmid-Grendelmeier, Holger J. Schünemann, A (Aziz) Sheikh, Nicola Scichilone, Juan Carlos Sisul, Mikhail Sofiev, Dirceu Solé, Talant Sooronbaev, Manuel Soto-Martinez, Manuel Soto-Quiros, Milan Sova, Jürgen Schwarze, Isabel Skypala, Charlotte Suppli Ulrik, Luis Taborda-Barata, Ana Todo-Bom, Maria J. Torres, Marylin Valentin-Rostan, Peter Valentin Tomazic, Antonio A. Valero, Sanna Toppila-Salmi, Ioanna Tsiligianni, Eva Untersmayr, Marilyn Urrutia-Pereira, Arunas Valiulis, Erkka Valovirta, Olivier Vandenplas, Maria Teresa Ventura, Pakit Vichyanond, Martin Wagenmann, Dana Wallace, Jolanta Walusiak-Skorupa, De Yun Wang, Susan Waserman, Gary Wong, Arzu Yorgancioglu, Osman M. Yusuf, Mario E. Zernotti, Luo Zhang, Mihaela Zidarn, Torsten Zuberbier, and Marek Jutel

Published
2021
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41. Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies

Author

Bousquet, Jean, Cristol, Jean-Paul, Czarlewski, Wienczyslawa, Anto, Josep M, Martineau, Adrian, Haahtela, Tari, Fonseca, Susana C, Iaccarino, Guido, Blain, Hubert, Fiocchi, Alessandro, Canonica, G Walter, Fonseca, Joao A, Vidal, Alain, Choi, Hak-Jong, Kim, Hyun Ju, Le Moing, Vincent, Reynes, Jacques, Sheikh, Aziz, Akdis, Cezmi A, Zuberbier, Torsten, Amir Hamzah Abdul Latiff, Baharudin, Abdullah, Werner, Aberer, Nancy, Abusada, Ian, Adcock, Alejandro, Afani, Ioana, Agache, Xenofon, Aggelidis, Jenifer, Agustin, Cezmi, A Akdis, Mübeccel, Akdis, Mona, Al-Ahmad, Abou Al-Zahab Bassam, Hussam, Alburdan, Oscar, Aldrey-Palacios, Emilio Alvarez Cuesta, Hiba Alwan Salman, Ashraf, Alzaabi, Salma, Amade, Gene, Ambrocio, Rosana, Angles, Isabella, Annesi-Maesano, Ignacio, J Ansotegui, Josep, M Anto, Paula Ara Bardajo, Stefania, Arasi, Margarete, Arrais, Hasan, Arshad, Maria-Cristina, Artesani, Estrella, Asayag, Francesca, Avolio, Khuzama, Azhari, Claus, Bachert, Diego, Bagnasco, Ilaria, Baiardini, Nissera, Bajrović, Petros, Bakakos, Sergio Bakeyala Mongono, Christine, Balotro-Torres, Sergio, Barba, Cristina, Barbara, Elsa, Barbosa, Bruno, Barreto, Joan, Bartra, Xavier, Basagana, Eric, D Bateman, Lkhagvaa, Battur, Anna, Bedbrook, Martín Bedolla Barajas, Bianca, Beghé, Antra, Bekere, Elizabeth, Bel, Ali Ben Kheder, Mikael, Benson, Elena-Camelia, Berghea, Karl-Christian, Bergmann, Roberto, Bernardini, David, Bernstein, Mike, Bewick, Slawomir, Bialek, Artur, Białoszewski, Thomas, Bieber, Nils, E Billo, Maria-Beatrice, Bilo, Carsten, Bindslev-Jensen, Leif, Bjermer, Hubert, Blain, Irina, Bobolea, Malgorzata Bochenska Marciniak, Christine, Bond, Attilio, Boner, Matteo, Bonini, Sergio, Bonini, Sinthia, Bosnic-Anticevich, Isabelle, Bosse, Sofia, Botskariova, Jacques, Bouchard, Louis-Philippe, Boulet, Rodolphe, Bourret, Philippe, Bousquet, Fulvio, Braido, Andrew, Briggs, Christopher, E Brightling, Jan, Brozek, Luisa, Brussino, Roland, Buhl, Roxana, Bumbacea, Rosalva, Buquicchio, María-Teresa Burguete Cabañas, Andrew, Bush, William, W Busse, Jeroen, Buters, Fernan, Caballero-Fonseca, Moïses, A Calderon, Mario, Calvo, Paulo, Camargos, Thierry, Camuzat, R Canevari, F, Antonio, Cano, G Walter Canonica, Arnaldo, Capriles-Hulett, Luis, Caraballo, Vicky, Cardona, Kai-Hakon, Carlsen, Jonas Carmona Pirez, Jorge, Caro, Warner, Carr, Pedro, Carreiro-Martins, Fredelita, Carreon-Asuncion, Ana-Maria, Carriazo, Carme Carrion, Y Ribas, Thomas, Casale, Mary-Ann, Castor, Elizabeth, Castro, G Caviglia, A, Lorenzo, Cecchi, Alfonso Cepeda Sarabia, Maciej, Chalubinski, Ramanathan, Chandrasekharan, Yoon-Seok, Chang, Victoria, Chato-Andeza, Lida, Chatzi, Christina, Chatzidaki, Niels, H Chavannes, Claudia Chaves Loureiro, Aurora-Alejandra Chavez Garcia, Marta, Chelninska, Yuzhi, Chen, Lei, Cheng, Sharon, Chinthrajah, Tomas, Chivato, Ekaterine, Chkhartishvili, George, Christoff, Henry, Chrystyn, Derek, K Chu, Antonio, Chua, Alexander, Chuchalin, Kian Fan Chung, Alberto, Cicerán, Cemal, Cingi, Giorgio, Ciprandi, Ieva, Cirule, Ana-Carla, Coelho, Enrico, Compalati, Jannis, Constantinidis, Jaime Correia de Sousa, Elisio Manuel Costa, David, Costa, María Del Carmen Costa Domínguez, André, Coste, Cottini, M, Linda, Cox, Carlos, Crisci, Maria Angiola Crivellaro, Alvaro, A Cruz, John, Cullen, Adnan, Custovic, Biljana, Cvetkovski, Wienczyslawa, Czarlewski, Gennaro, D'Amato, Jane da Silva, Ronald, Dahl, Sven-Erik, Dahlen, Vasilis, Daniilidis, Louei Darjazini Nahhas, Ulf, Darsow, Janet, Davies, Frédéric de Blay, Giulia De Feo, Eloisa De Guia, José-Ricardo De la Torre Navarrete, Chato De Los Santos, Esteban De Manuel Keenoy, Govert De Vries, Diana, Deleanu, Pascal, Demoly, Judah, Denburg, Philippe, Devillier, Alain, Didier, Sanja Dimic Janjic, Maria, Dimou, Anh Tuan Dinh-Xuan, Ratko, Djukanovic, Maria Do Ceu Texeira, Dejan, Dokic, Margarita Gabriela Domínguez Silva, Habib, Douagui, Nikolaos, Douladiris, Maria, Doulaptsi, Gérard, Dray, Ruta, Dubakiene, Eve, Dupas, Stephen, Durham, Marzia, Duse, Mark, Dykewicz, Didier, Ebo, Natalija, Edelbaher, Thomas, Eiwegger, Patrik, Eklund, Yehia, El-Gamal, Zeinab, A El-Sayed, Shereen, S El-Sayed, Magda, El-Seify, Regina, Emuzyte, Lourdes, Enecilla, Marina, Erhola, Heidilita, Espinoza, Jesús Guillermo Espinoza Contreras, John, Farrell, Lenora, Fernandez, Paola Fimbres Jimenez, Antje Fink Wagner, Alessandro, Fiocchi, Wytske, J Fokkens, Lenia, Folletti, Joao, A Fonseca, Jean-François, Fontaine, Francesco, Forastiere, Jose Miguel Fuentes Pèrez, Emily, Gaerlan-Resureccion, Mina, Gaga, José Luis Gálvez Romero, Amiran, Gamkrelidze, Alexis, Garcia, Cecilia Yvonne García Cobas, María de la Luz Hortensia García Cruz, Valeria Garcia Ortiz, Jacques, Gayraud, Matteo, Gelardi, Bilun, Gemicioglu, Dimitra, Gennimata, Sonya, Genova, José, Gereda, Roy Gerth van Wijk, Antonio, Giuliano, René-Maximiliano, Gomez, Miguel-Ange Gonzalez Ballester, Sandra González Diaz, Maia, Gotua, Christos, Grigoreas, Ineta, Grisle, Marta, Guidacci, Nick, Guldemond, Zdenek, Gutter, Antonieta, Guzmán, Tari, Haahtela, Ramsa, Halloum, David, Halpin, Eckard, Hamelmann, Suleiman, Hammadi, Richard, Harvey, Enrico, Heffler, Joachim, Heinrich, Adnan, Hejjaoui, Birthe, Hellquist-Dahl, Luiana Hernández Velázquez, Mark, Hew, Elham, Hossny, Peter, Howarth, Martin, Hrubiško, Yunuen Rocío Huerta Villalobos, Marc, Humbert, Salina, Husain, Michael, Hyland, Guido, Iaccarino, Moustafa, Ibrahim, Nataliya, Ilina, Maddalena, Illario, Cristoforo, Incorvaia, Antonio, Infantino, Carla, Irani, Zhanat, Ispayeva, Juan Carlos Ivancevich, Edgardo Ej Jares, Deborah, Jarvis, Ewa, Jassem, Klemen, Jenko, Rubén Darío Jiméneracruz Uscanga, Sebastian, L Johnston, Guy, Joos, Maja, Jošt, Kaja, Julge, Ki-Suck, Jung, Jocelyne, Just, Marek, Jutel, Igor, Kaidashev, Omer, Kalayci, Fuat, Kalyoncu, Jeni, Kapsali, Przemyslaw, Kardas, Jussi, Karjalainen, Carmela, A Kasala, Michael, Katotomichelakis, Loreta, Kavaliukaite, Kazi, S Bennoor, Thomas, Keil, Paul, Keith, Musa, Khaitov, Nikolai, Khaltaev, You-Young, Kim, Bruce, Kirenga, Jorg, Kleine-Tebbe, Ludger, Klimek, Fanny, W Ko, Bernard Koffi N'Goran, Evangelia, Kompoti, Peter, Kopač, Gerard, Koppelman, Anja Koren Jeverica, Seppo, Koskinen, Mitja, Košnik, Tomasz, Kostka, Kosta, V Kostov, Marek, L Kowalski, Tanya, Kralimarkova, Karmen Kramer Vrščaj, Helga, Kraxner, Samo, Kreft, Vicky, Kritikos, Dmitry, Kudlay, Mikael, Kuitunen, Inger, Kull, Piotr, Kuna, Maciej, Kupczyk, Violeta, Kvedariene, Marialena, Kyriakakou, Nika, Lalek, Massimo, Landi, Stephen, Lane, Désiree, E Larenas-Linnemann, Susanne, Lau, Daniel, Laune, Jorge, Lavrut, Lan, Le, Martina, Lenzenhuber, Gualtiero, Leo, Marcus, Lessa, Michael, Levin, Jing, Li, Philip, Lieberman, Giuseppe, Liotta, Brian, Lipworth, Xuandao, Liu, Rommel, Lobo, Karin, C Lodrup Carlsen, Carlo, Lombardi, Renaud, Louis, Stelios, Loukidis, Olga, Lourenço, Jorge, A Luna Pech, Bojan, Madjar, Enrico, Maggi, Antoine, Magnan, Bassam, Mahboub, Alpana, Mair, Anke-Hilse Maitland van der Zee, Mika, Makela, Michael, Makris, Hans-Jorgen, Malling, Mariana, Mandajieva, Patrick, Manning, Manolis, Manousakis, Pavlos, Maragoudakis, Gianluigi, Marseglia, Gailen, Marshall, Mohammad Reza Masjedi, Jorge, F Máspero, Juan José Matta Campos, Marcus, Maurer, Sandra, Mavale-Manuel, Cem, Meço, Erik, Melén, Giovanni, Melioli, Elisabete, Melo-Gomes, Eli, O Meltzer, Enrica, Menditto, Andrew, Menzies-Gow, Hans, Merk, Jean-Pierre, Michel, Yann, Micheli, Neven, Miculinic, Luís, Midão, Florin, Mihaltan, Nikolaos, Mikos, Manlio, Milanese, Branislava, Milenkovic, Dimitrios, Mitsias, Bassem, Moalla, Giuliana, Moda, María Dolores Mogica Martínez, Yousser, Mohammad, Frances-Montserrat, Moharra, Mostafa, Moin, Mathieu, Molimard, Isabelle, Momas, Monique, Mommers, Alessandro, Monaco, Stephen, Montefort, Lucia-Elvira, Montenegro, Riccardo, Monti, Dory, Mora, Mario, Morais-Almeida, Ralph, Mösges, Badr Eldin Mostafa, Joaquim, Mullol, Lars, Münter, Antonella, Muraro, Ruth, Murray, Antonio, Musarra, Tihomir, Mustakov, Robert, Naclerio, Kari, C Nadeau, Rachel, Nadif, Alla, Nakonechna, Leyla, Namazova-Baranova, Gretchen, Navarro-Locsin, Hugo, Neffen, Kristof, Nekam, Angelos, Neou, Eustachio, Nettis, Daniel, Neuberger, Laurent, Nicod, Stefania, Nicola, Verena, Niederberger-Leppin, Marek, Niedoszytko, Antonio, Nieto, Ettore, Novellino, Elizabete, Nunes, Dieudonné, Nyembue, Robyn, E O'Hehir, Cvetanka, Odjakova, Ken, Ohta, Yoshitaka, Okamoto, Kimi, Okubo, Brian, Oliver, Gabrielle, L Onorato, Maria Pia Orru, Solange, Ouédraogo, Kampadilemba, Ouoba, Francisco-Javier, Padilla, Pier Luigi Paggiaro, Aris, Pagkalos, Pajno, Giovanni Battista, Gianni, Pala, P Palaniappan, S, Isabella, Pali-Schöll, Susanna, Palkonen, Stephen, Palmer, Carmen Panaitescu Bunu, Petr, Panzner, Nikos, G Papadopoulos, Vasilis, Papanikolaou, Alberto, Papi, Bojidar, Paralchev, Giannis, Paraskevopoulos, Hae-Sim, Park, Giovanni, Passalacqua, Vincenzo, Patella, Ian, Pavord, Ruby, Pawankar, Soren, Pedersen, Susete, Peleve, Simona, Pellegino, Ana, Pereira, Mariana, Pereira, Tamara, Pérez, Andrea, Perna, Diego, Peroni, Oliver, Pfaar, Nhân, Pham-Thi, Bernard, Pigearias, Isabelle, Pin, Konstantina, Piskou, Constantinos, Pitsios, Davor, Plavec, Dagmar, Poethig, Wolfgang, Pohl, Antonija Poplas Susic, Todor, A Popov, Fabienne, Portejoie, Paul, Potter, Lars, Poulsen, Alexandra, Prados-Torres, Fotis, Prarros, David, Price, Emmanuel, Prokopakis, Francesca, Puggioni, Elisa, Puig-Domenech, Robert, Puy, Klaus, Rabe, Silvia, Rabotti, Filip, Raciborski, Josephine, Ramos, Cristina, Recalcati, Marysia, T Recto, Shereen, M Reda, Frederico, S Regateiro, Norbert, Reider, Sietze, Reitsma, Susana, Repka-Ramirez, Erminia, Ridolo, Janet, Rimmer, Daniela Rivero Yeverino, José Angelo Rizzo, Carlos, Robalo-Cordeiro, Graham, Roberts, Karen, Robles, Nicolas, Roche, Mónica Rodríguez González, Eréndira Rodríguez Zagal, Giovanni, Rolla, Christine, Rolland, Regina, Roller-Wirnsberger, Miguel Roman Rodriguez, Antonino, Romano, Jan, Romantowski, Philippe, Rombaux, Joel, Romualdez, Jose, Rosado-Pinto, Nelson, Rosario, Lanny, Rosenwasser, Oliviero, Rossi, Menachem, Rottem, Philip, W Rouadi, Nikoleta, Rovina, Irma Rozman Sinur, Mauricio, Ruiz, Lucy Tania Ruiz Segura, Dermot, Ryan, Hironori, Sagara, Daiki, Sakai, Daiju, Sakurai, Wafaa, Saleh, Johanna, Salimaki, Konstantinos, Samitas, Boleslaw, Samolinski, María Guadalupe Sánchez Coronel, Mario, Sanchez-Borges, Jaime, Sanchez-Lopez, Melissa, Sansonna, Codrut, Sarafoleanu, Faradiba Sarquis Serpa, Joaquin, Sastre, Eleonora, Savi, Agne, Savonyte, Bisher, Sawaf, Glenis, K Scadding, Sophie, Scheire, Peter, Schmid-Grendelmeier, Juan Francisco Schuhl, Holger, Schunemann, Maria, Schvalbová, Jorgen, Schwarze, Nicola, Scichilone, Gianenrico, Senna, Cecilia, Sepúlveda, Elie, Serrano, Sara, Shamai, Aziz, Sheikh, Mike, Shields, Vasil, Shishkov, Nikos, Siafakas, Alexander, Simeonov, Estelle Fer Simons, Juan Carlos Sisul, Brigita, Sitkauskiene, Ingelbjorg, Skrindo, Tanja Soklič Košak, Dirceu, Solé, Martin, Sondermann, Talant, Sooronbaev, Manuel, Soto-Martinez, Manuel, Soto-Quiros, Barnaro Sousa Pinto, Milan, Sova, Michael, Soyka, Krzysztof, Specjalski, Annette, Sperl, Otto, Spranger, Sofia, Stamataki, Lina, Stefanaki, Cristiana, Stellato, Rafael, Stelmach, Timo, Strandberg, Petra, Stute, Abirami, Subramaniam, Charlotte Suppli Ulrik, Michael, Sutherland, Silvia, Sylvestre, Aikaterini, Syrigou, Luis Taborda Barata, Nadejda, Takovska, Rachel, Tan, Frances, Tan, Vincent, Tan, Ing Ping Tang, Masami, Taniguchi, Line, Tannert, Pongsakorn, Tantilipikorn, Jessica, Tattersall, Filippo, Tesi, Uta, Thieme, Carel, Thijs, Mike, Thomas, Teresa, To, Ana Maria Todo-Bom, Alkis, Togias, Peter-Valentin, Tomazic, Vesna, Tomic-Spiric, Sanna, Toppila-Salmi, Maria-José Torres Jaen, Elina, Toskala, Massimo, Triggiani, Nadja, Triller, Katja, Triller, Ioanna, Tsiligianni, Uberti, M, Ruxandra, Ulmeanu, Jure, Urbancic, Marilyn Urrutia Pereira, Martina, Vachova, Felipe, Valdés, Rudolf, Valenta, Marylin Valentin Rostan, Antonio, Valero, Arunas, Valiulis, Mina, Vallianatou, Erkka, Valovirta, Michiel Van Eerd, Eric Van Ganse, Marianne van Hage, Olivier, Vandenplas, Tuula, Vasankari, Dafina, Vassileva, Cesar Velasco Munoz, Maria Teresa Ventura, Cécilia, Vera-Munoz, Frédéric, Viart, Dilyana, Vicheva, Pakit, Vichyanond, Petra, Vidgren, Giovanni, Viegi, Claus, Vogelmeier, Leena Von Hertzen, Theodoros, Vontetsianos, Dimitris, Vourdas, Vu Tran Thien Quan, Martin, Wagenmann, Samantha, Walker, Dana, Wallace, Yun De Wang, Susan, Waserman, Katrin, Wehner, Magnus, Wickman, Sian, Williams, Dennis, Williams, Nicola, Wilson, Gary, Wong, Kent, Woo, Lucyna, Wozniak, John, Wright, Piotr, Wroczynski, Paraskevi, Xepapadaki, Plamen, Yakovliev, Masao, Yamaguchi, Kwok, Yan, Yoke Yeow Yap, Mais, Yassin, Barbara, Yawn, Panayiotis, Yiallouros, Arzu, Yorgancioglu, Shigemi, Yoshihara, Ian, Young, Osman, B Yusuf, Asghar, Zaidi, Fares, Zaitoun, Petra, Zalud, Heather, Zar, T Zedda, M, Mario, E Zernotti, Luo, Zhang, Nanshan, Zhong, Mihaela, Zidarn, Torsten, Zuberbier, Celia, Zubrinich, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Barts & The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki University Central Hospital [Finland] (HUCH), Departamento de Geociencias, Ambiente e Ordenamento do Territorio (DGAOT), Universidade do Porto = University of Porto, University of Naples Federico II = Università degli studi di Napoli Federico II, Euromov (EuroMov), Université de Montpellier (UM), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Center of Research in Health Technologies and Information Systems (CINTESIS), AgroParisTech, World Institute of Kimchi [Gwangju], Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Edinburgh, Universität Zürich [Zürich] = University of Zurich (UZH), Humboldt-Universität zu Berlin, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Helsinki, Universidade do Porto, University of Naples Federico II, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), MORNET, Dominique, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bousquet J., Cristol J.-P., Czarlewski W., Anto J.M., Martineau A., Haahtela T., Fonseca S.C., Iaccarino G., Blain H., Fiocchi A., Canonica G.W., Fonseca J.A., Vidal A., Choi H.-J., Kim H.J., Le Moing V., Reynes J., Sheikh A., Akdis C.A., Zuberbier T., Abdul Latiff A.H., Abdullah B., Aberer W., Abusada N., Adcock I., Afani A., Agache I., Aggelidis X., Agustin J., Akdis M., Al-Ahmad M., Al-Zahab Bassam A., Alburdan H., Aldrey-Palacios O., Alvarez Cuesta E., Alwan Salman H., Alzaabi A., Amade S., Ambrocio G., Angles R., Annesi-Maesano I., Ansotegui I.J., Ara Bardajo P., Arasi S., Arrais M., Arshad H., Artesani M.-C., Asayag E., Avolio F., Azhari K., Bachert C., Bagnasco D., Baiardini I., Bajrovic N., Bakakos P., Bakeyala Mongono S., Balotro-Torres C., Barba S., Barbara C., Barbosa E., Barreto B., Bartra J., Basagana X., Bateman E.D., Battur L., Bedbrook A., Bedolla Barajas M., Beghe B., Bekere A., Bel E., Ben Kheder A., Benson M., Berghea E.-C., Bergmann K.-C., Bernardini R., Bernstein D., Bewick M., Bialek S., Bialoszewski A., Bieber T., Billo N.E., Bilo M.-B., Bindslev-Jensen C., Bjermer L., Bobolea I., Bochenska Marciniak M., Bond C., Boner A., Bonini M., Bonini S., Bosnic-Anticevich S., Bosse I., Botskariova S., Bouchard J., Boulet L.-P., Bourret R., Bousquet P., Braido F., Briggs A., Brightling C.E., Brozek J., Brussino L., Buhl R., Bumbacea R., Buquicchio R., Burguete Cabanas M.-T., Bush A., Busse W.W., Buters J., Caballero-Fonseca F., Calderon M.A., Calvo M., Camargos P., Camuzat T., Canevari F., Cano A., Canonican G.W., Capriles-Hulett A., Caraballo L., Cardona V., Carlsen K.-H., Carmona Pirez J., Caro J., Carr W., Carreiro-Martins P., Carreon-Asuncion F., Carriazo A.-M., CarrionyRibas C., Casale T., Castor M.-A., Castro E., Caviglia A.G., Cecchi L., Cepeda Sarabia A., Chalubinski M., Chandrasekharan R., Chang Y.-S., Chato-Andeza V., Chatzi L., Chatzidaki C., Chavannes N.H., Chaves Loureiro C., Chavez Garcia A.-A., Chelninska M., Chen Y., Cheng L., Chinthrajah S., Chivato T., Chkhartishvili E., Christoff G., Chrystyn H., Chu D.K., Chua A., Chuchalin A., Chung K.F., Ciceran A., Cingi C., Ciprandi G., Cirule I., Coelho A.-C., Compalati E., Constantinidis J., Correia de Sousa J., Costa E.M., Costa D., del Carmen Costa Dominguez M., Coste A., Cottini M., Cox L., Crisci C., Crivellaro M.A., Cruz A.A., Cullen J., Custovic A., Cvetkovski B., D'Amato G., da Silva J., Dahl R., Dahlen S.-E., Daniilidis V., Darjazini Nahhas L., Darsow U., Davies J., de Blay F., De Feo G., De Guia E., De la Torre Navarrete J.-R., De los Santos C., De Manuel Keenoy E., De Vries G., Deleanu D., Demoly P., Denburg J., Devillier P., Didier A., Dimic Janjic S., Dimou M., Dinh-Xuan A.T., Djukanovic R., Do Ceu Texeira M., Dokic D., Dominguez Silva M.G., Douagui H., Douladiris N., Doulaptsi M., Dray G., Dubakiene R., Dupas E., Durham S., Duse M., Dykewicz M., Ebo D., Edelbaher N., Eiwegger T., Eklund P., El-Gamal Y., El-Sayed Z.A., El-Sayed S.S., El-Seify M., Emuzyte R., Enecilla L., Erhola M., Espinoza H., Espinoza Contreras J.G., Farrell J., Fernandez L., Fimbres Jimenez P., Fink Wagner A., Fokkens W.J., Folletti L., Fontaine J.-F., Forastiere F., Fuentes Perez J.M., Gaerlan-Resureccion E., Gaga M., Galvez Romero J.L., Gamkrelidze A., Garcia A., Garcia Cobas C.Y., de la Luz Hortensia Garcia Cruz M., Ortiz V.G., Gayraud J., Gelardi M., Gemicioglu B., Gennimata D., Genova S., Gereda J., Gerth van Wijk R., Giuliano A., Gomez R.-M., Gonzalez Ballester M.-A., Gonzalez Diaz S., Gotua M., Grigoreas C., Grisle I., Guidacci M., Guldemond N., Gutter Z., Guzman A., Halloum R., Halpin D., Hamelmann E., Hammadi S., Harvey R., Heffler E., Heinrich J., Hejjaoui A., Hellquist-Dahl B., Hernandez Velazquez L., Hew M., Hossny E., Howarth P., Hrubisko M., Huerta Villalobos Y.R., Humbert M., Husain S., Hyland M., Ibrahim M., Ilina N., Illario M., Incorvaia C., Infantino A., Irani C., Ispayeva Z., Ivancevich J.C., Jares E.E., Jarvis D., Jassem E., Jenko K., Jimeneracruz Uscanga R.D., Johnston S.L., Joos G., Jost M., Julge K., Jung K.-S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu F., Kapsali J., Kardas P., Karjalainen J., Kasala C.A., Katotomichelakis M., Kavaliukaite L., Bennoor K.S., Keil T., Keith P., Khaitov M., Khaltaev N., Kim Y.-Y., Kirenga B., Kleine-Tebbe J., Klimek L., Ko F.W., Koffi N'Goran B., Kompoti E., Kopac P., Koppelman G., Koren Jeverica A., Koskinen S., Kosnik M., Kostka T., Kostov K.V., Kowalski M.L., Kralimarkova T., Kramer Vrscaj K., Kraxner H., Kreft S., Kritikos V., Kudlay D., Kuitunen M., Kull I., Kuna P., Kupczyk M., Kvedariene V., Kyriakakou M., Lalek N., Landi M., Lane S., Larenas-Linnemann D.E., Lau S., Laune D., Lavrut J., Le L., Lenzenhuber M., Leo G., Lessa M., Levin M., Li J., Lieberman P., Liotta G., Lipworth B., Liu X., Lobo R., Lodrup Carlsen K.C., Lombardi C., Louis R., Loukidis S., Lourenco O., Luna Pech J.A., Madjar B., Maggi E., Magnan A., Mahboub B., Mair A., Maitland van der Zee A.-H., Makela M., Makris M., Malling H.-J., Mandajieva M., Manning P., Manousakis M., Maragoudakis P., Marseglia G., Marshall G., Masjedi M.R., Maspero J.F., Matta Campos J.J., Maurer M., Mavale-Manuel S., Meco C., Melen E., Melioli G., Melo-Gomes E., Meltzer E.O., Menditto E., Menzies-Gow A., Merk H., Michel J.-P., Micheli Y., Miculinic N., Midao L., Mihaltan F., Mikos N., Milanese M., Milenkovic B., Mitsias D., Moalla B., Moda G., Mogica Martinez M.D., Mohammad Y., Moharra F.-M., Moin M., Molimard M., Momas I., Mommers M., Monaco A., Montefort S., Montenegro L.-E., Monti R., Mora D., Morais-Almeida M., Mosges R., Mostafa B.E., Mullol J., Munter L., Muraro A., Murray R., Musarra A., Mustakov T., Naclerio R., Nadeau K.C., Nadif R., Nakonechna A., Namazova-Baranova L., Navarro-Locsin G., Neffen H., Nekam K., Neou A., Nettis E., Neuberger D., Nicod L., Nicola S., Niederberger-Leppin V., Niedoszytko M., Nieto A., Novellino E., Nunes E., Nyembue D., O'Hehir R.E., Odjakova C., Ohta K., Okamoto Y., Okubo K., Oliver B., Onorato G.L., Orru M.P., Ouedraogo S., Ouoba K., Padilla F.-J., Paggiaro P.L., Pagkalos A., Pajno G., Pala G., Palaniappan S., Pali-Scholl I., Palkonen S., Palmer S., Panaitescu Bunu C., Panzner P., Papadopoulos N.G., Papanikolaou V., Papi A., Paralchev B., Paraskevopoulos G., Park H.-S., Passalacqua G., Patella V., Pavord I., Pawankar R., Pedersen S., Peleve S., Pellegino S., Pereira A., Pereira M., Perez T., Perna A., Peroni D., Pfaar O., Pham-Thi N., Pigearias B., Pin I., Piskou K., Pitsios C., Plavec D., Poethig D., Pohl W., Poplas Susic A., Popov T.A., Portejoie F., Potter P., Poulsen L., Prados-Torres A., Prarros F., Price D., Prokopakis E., Puggioni F., Puig-Domenech E., Puy R., Rabe K., Rabotti S., Raciborski F., Ramos J., Recalcati C., Recto M.T., Reda S.M., Regateiro F.S., Reider N., Reitsma S., Repka-Ramirez S., Ridolo E., Rimmer J., Rivero Yeverino D., Rizzo J.A., Robalo-Cordeiro C., Roberts G., Robles K., Roche N., Rodriguez Gonzalez M., Rodriguez Zagal E., Rolla G., Rolland C., Roller-Wirnsberger R., Roman Rodriguez M., Romano A., Romantowski J., Rombaux P., Romualdez J., Rosado-Pinto J., Rosario N., Rosenwasser L., Rossi O., Rottem M., Rouadi P.W., Rovina N., Rozman Sinur I., Ruiz M., Ruiz Segura L.T., Ryan D., Sagara H., Sakai D., Sakurai D., Saleh W., Salimaki J., Samitas K., Samolinski B., Sanchez Coronel M.G., Sanchez-Borges M., Sanchez-Lopez J., Sansonna M., Sarafoleanu C., Sarquis Serpa F., Sastre J., Savi E., Savonyte A., Sawaf B., Scadding G.K., Scheire S., Schmid-Grendelmeier P., Schuhl J.F., Schunemann H., Schvalbova M., Schwarze J., Scichilone N., Senna G., Sepulveda C., Serrano E., Shamai S., Shields M., Shishkov V., Siafakas N., Simeonov A., Simons E.F., Sisul J.C., Sitkauskiene B., Skrindo I., Soklic Kosak T., Sole D., Sondermann M., Sooronbaev T., Soto-Martinez M., Soto-Quiros M., Pinto B.S., Sova M., Soyka M., Specjalski K., Sperl A., Spranger O., Stamataki S., Stefanaki L., Stellato C., Stelmach R., Strandberg T., Stute P., Subramaniam A., Suppli Ulrik C., Sutherland M., Sylvestre S., Syrigou A., Taborda Barata L., Takovska N., Tan R., Tan F., Tan V., Tang I.P., Taniguchi M., Tannert L., Tantilipikorn P., Tattersall J., Tesi F., Thieme U., Thijs C., Thomas M., To T., Todo-Bom A.M., Togias A., Tomazic P.-V., Tomic-Spiric V., Toppila-Salmi S., Torres Jaen M.-J., Toskala E., Triggiani M., Triller N., Triller K., Tsiligianni I., Uberti M., Ulmeanu R., Urbancic J., Urrutia Pereira M., Vachova M., Valdes F., Valenta R., Valentin Rostan M., Valero A., Valiulis A., Vallianatou M., Valovirta E., Van Eerd M., Van Ganse E., van Hage M., Vandenplas O., Vasankari T., Vassileva D., Velasco Munoz C., Ventura M.T., Vera-Munoz C., Viart F., Vicheva D., Vichyanond P., Vidgren P., Viegi G., Vogelmeier C., Von Hertzen L., Vontetsianos T., Vourdas D., Tran Thien Quan V., Wagenmann M., Walker S., Wallace D., De Wang Y., Waserman S., Wehner K., Wickman M., Williams S., Williams D., Wilson N., Wong G., Woo K., Wozniak L., Wright J., Wroczynski P., Xepapadaki P., Yakovliev P., Yamaguchi M., Yan K., Yap Y.Y., Yassin M., Yawn B., Yiallouros P., Yorgancioglu A., Yoshihara S., Young I., Yusuf O.B., Zaidi A., Zaitoun F., Zalud P., Zar H., Zedda M.T., Zernotti M.E., Zhang L., Zhong N., and Zidarn M.

Subjects
MAPK/ERK pathway, ARIA group, Allergy, [SDV]Life Sciences [q-bio], NF-KAPPA-B, debelost, Review, Pharmacology, Resveratrol, PROTECTS, chemistry.chemical_compound, 0302 clinical medicine, RESPIRATORY SYNDROME CORONAVIRUS, ENDOPLASMIC-RETICULUM STRESS, Medicine and Health Sciences, Immunology and Allergy, Medicine, OXIDATIVE STRESS, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, 2. Zero hunger, 0303 health sciences, RESPIRATORY, INSULIN-RESISTANCE, Muscle cell proliferation, SULFORAPHANE, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, SIGNALING PATHWAY, Signal transduction, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, NRF2 ACTIVATORS, MUSCLE-CELL PROLIFERATION, Immunology, 610 Medicine & health, Lung injury, Settore MED/10 - Malattie Dell'Apparato Respiratorio, ACUTE LUNG INJURY, 03 medical and health sciences, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, udc:616.9, odpornost proti inzulinu, SULFORAPHANE PROTECTS, Transcription factor, PI3K/AKT/mTOR pathway, 030304 developmental biology, Science & Technology, business.industry, SARS-CoV-2, food, medicine.disease, chemistry, hranila, SYNDROME CORONAVIRUS, business, hrana, GREEN TEA
Abstract

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.

Published
2020

42. Rapid generation of durable B cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 and convalescence

Author

Emily S.J. Edwards, P. Mark Hogarth, Stephanie Stojanovic, Heidi E. Drummer, Nirupama Varese, James H McMahon, Robyn E O'Hehir, Anton Y. Peleg, Irene Boo, Menno C. van Zelm, Pei M. Aui, and Gemma E. Hartley

Subjects
0301 basic medicine, Adult, Male, media_common.quotation_subject, T cell, viruses, Immunology, Antibodies, Viral, Immunoglobulin G, 03 medical and health sciences, 0302 clinical medicine, Immunophenotyping, Protein Domains, Immunity, medicine, Coronavirus Nucleocapsid Proteins, Humans, 030212 general & internal medicine, skin and connective tissue diseases, B cell, media_common, Aged, B-Lymphocytes, biology, SARS-CoV-2, Convalescence, fungi, COVID-19, General Medicine, Middle Aged, Phosphoproteins, 3. Good health, body regions, Coronavirus, 030104 developmental biology, medicine.anatomical_structure, Immunoglobulin M, Spike Glycoprotein, Coronavirus, biology.protein, Female, Antibody, Immunologic Memory, Reports
Abstract

Memory B cells specific for SARS-CoV-2 spike and nucleocapsid proteins persist in peripheral blood after recovery from COVID-19., Lasting immunity following SARS-CoV-2 infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells. Therefore, we generated fluorescently-labeled tetramers of the spike receptor binding domain (RBD) and nucleocapsid protein (NCP) to determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem cells in COVID-19 patients. A total of 36 blood samples were obtained from 25 COVID-19 patients between 4 and 242 days post-symptom onset including 11 paired samples. While serum IgG to RBD and NCP was identified in all patients, antibody levels began declining at 20 days post-symptom onset. RBD- and NCP-specific Bmem cells predominantly expressed IgM+ or IgG1+ and continued to rise until 150 days. RBD-specific IgG+ Bmem were predominantly CD27+, and numbers significantly correlated with circulating follicular helper T cell numbers. Thus, the SARS-CoV-2 antibody response contracts in convalescence with persistence of RBD- and NCP-specific Bmem cells. Flow cytometric detection of SARS-CoV-2-specific Bmem cells enables detection of long-term immune memory following infection or vaccination for COVID-19.

Published
2020

43. Trimethoprim anaphylaxis confirmed by a novel basophil activation test

Author

Celia Zubrinich, Mark Hew, Marsus Pumar, Nirupama Varese, and Robyn E O'Hehir

Subjects
Pulmonary and Respiratory Medicine, business.industry, Immunology, Anti-Infective Agents, Urinary, Basophil Degranulation Test, Middle Aged, medicine.disease, Trimethoprim, Drug Hypersensitivity, Basophil activation, Urinary Tract Infections, medicine, Humans, Immunology and Allergy, Female, business, Anaphylaxis, Skin Tests, medicine.drug
Published
2021

44. Rapid and lasting generation of B-cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 disease and convalescence

Author

Nirupama Priya Varese, James H McMahon, Irene Boo, Esj Edwards, Stephanie Stojanovic, Mark Hogarth, Pei M. Aui, Gemma E. Hartley, M C van Zelm, Robyn E O'Hehir, Heidi E. Drummer, and Anton Y. Peleg

Subjects
medicine.diagnostic_test, T cell, Biology, Serology, Flow cytometry, medicine.anatomical_structure, Immune system, Immunophenotyping, Immunity, Immunology, medicine, biology.protein, Antibody, B cell
Abstract

BackgroundLasting immunity to SARS-CoV-2 following infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells.ObjectiveTo determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem cells in COVID-19 patients.MethodsRecombinant spike receptor binding domain (RBD) and nucleocapsid protein (NCP) were produced for ELISA-based serology, and biotinylated for fluorescent tetramer generation to identify SARS-CoV-2-specific Bmem cells by flow cytometry with a panel of 13 mAbs. 36 blood samples were obtained from 25 COVID-19 patients (11 paired) between 4-242 days post-symptom onset for detection of neutralizing antibodies, IgG serology and flow cytometry.ResultsThe recombinant RBD and NCP were specifically recognized by serum IgG in all patients and reactivity declined >20 days post-symptom onset. All patients had detectable RBD- and NCP-specific Bmem cells at 8.23-267.6 cells/ml of blood (0.004-0.13% of B cells) regardless of sampling time. RBD- and NCP-specific Bmem cells predominantly expressed IgM or IgG1, with the latter formed slightly later than the former. RBD-specific IgG+Bmem were predominantly CD27+, and numbers significantly correlated with circulating follicular helper T cell numbers.ConclusionRBD- and NCP-specific Bmem cells persisted for 8 months, indicating that the decline in serum antibodies after 1 month does not indicate waning of immunity but a contraction of the immune response. Flowcytometric detection of SARS-CoV-2-specific Bmem cells enables detection of long-term functional immunity following infection or vaccination for COVID-19.

Published
2020

45. BIOMARKERS IN THE DIAGNOSIS AND THERAPY OF ALLERGIC DISEASES AND ASTHMA

Author

Heimo Breiteneder, De Yun Wang, Kari C. Nadeau, María Luisa de Torres, Zuzana Diamant, Robyn E O'Hehir, Liam O'Mahony, Luo Zhang, Claudia Traidl-Hoffmann, Oliver Pfaar, Ioana Agache, Thomas Eiwegger, Wytske Fokkens, Cezmi A. Akdis, and Yaqi Peng

Subjects
medicine.medical_specialty, biology, business.industry, Disease, Atopic dermatitis, Immunoglobulin E, medicine.disease, Food allergy, biology.protein, medicine, Microbiome, Personalized medicine, Intensive care medicine, business, Anaphylaxis, Asthma
Abstract

Modern healthcare requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of the distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long-lasting therapies. Escalating healthcare costs together with questions on the efficacy of the current management of allergic diseases requires further development of a biomarker-driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen-immunotherapy with a special emphasis on specific IgE, microbiome and epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers.

Published
2020

46. Novel basophil activation test in the diagnosis of povidone anaphylaxis

Author

Mark Hew, Nirupama Varese, Celia Zubrinich, Kavitha Garuna Murthee, and Robyn E O'Hehir

Subjects
Pulmonary and Respiratory Medicine, biology, business.industry, Immunology, Basophil degranulation test, Basophil Degranulation Test, Povidone, Immunoglobulin E, Middle Aged, medicine.disease, Basophils, Basophil activation, medicine, biology.protein, Pharmaceutic Aids, Immunology and Allergy, Humans, Female, business, Anaphylaxis
Published
2020

47. Effect of structural stability on endolysosomal degradation and T-cell reactivity of major shrimp allergen tropomyosin

Author

Swati Iyer, Sandra Scheiblhofer, Yoan Machado, Sandip D. Kamath, Christopher M. Johnson, Richard Weiss, Isabella Anna Joubert, Thomas McLean, Heidi Hofer, Peter Briza, Andreas L. Lopata, Paul A. Ramsland, Jennifer M. Rolland, Fatima Ferreira, Michael Wallner, Robyn E O'Hehir, Aya C Taki, and Josef Thalhamer

Subjects
0301 basic medicine, shrimp allergy, T-Lymphocytes, Immunology, Peptide, Tropomyosin, Cross Reactions, Immunoglobulin E, medicine.disease_cause, Cross-reactivity, Epitope, Food Allergy and Gastrointestinal Disease, endolysosomal degradation, 03 medical and health sciences, Mice, 0302 clinical medicine, Allergen, biology.animal, medicine, Immunology and Allergy, Animals, Peptide sequence, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Cockroach, biology, Chemistry, Proteolytic enzymes, Protein primary structure, T cell, Allergens, cross‐reactivity, 030104 developmental biology, 030228 respiratory system, Biochemistry, biology.protein, Original Article, Antibody, ORIGINAL ARTICLES, Function (biology)
Abstract

Background Tropomyosins are highly conserved proteins, an attribute that forms the molecular basis for their IgE antibody cross‐reactivity. Despite sequence similarities, their allergenicity varies greatly between ingested and inhaled invertebrate sources. In this study, we investigated the relationship between the structural stability of different tropomyosins, their endolysosomal degradation patterns, and T‐cell reactivity. Methods We investigated the differences between four tropomyosins—the major shrimp allergen Pen m 1 and the minor allergens Der p 10 (dust mite), Bla g 7 (cockroach), and Ani s 3 (fish parasite)—in terms of IgE binding, structural stability, endolysosomal degradation and subsequent peptide generation, and T‐cell cross‐reactivity in a BALB/c murine model. Results Tropomyosins displayed different melting temperatures, which did not correlate with amino acid sequence similarities. Endolysosomal degradation experiments demonstrated differential proteolytic digestion, as a function of thermal stability, generating different peptide repertoires. Pen m 1 (Tm 42°C) and Der p 10 (Tm 44°C) elicited similar patterns of endolysosomal degradation, but not Bla g 7 (Tm 63°C) or Ani s 3 (Tm 33°C). Pen m 1–specific T‐cell clones, with specificity for regions highly conserved in all four tropomyosins, proliferated weakly to Der p 10, but did not proliferate to Bla g 7 and Ani s 3, indicating lack of T‐cell epitope cross‐reactivity. Conclusions Tropomyosin T‐cell cross‐reactivity, unlike IgE cross‐reactivity, is dependent on structural stability rather than amino acid sequence similarity. These findings contribute to our understanding of cross‐sensitization among different invertebrates and design of suitable T‐cell peptide‐based immunotherapies for shrimp and related allergies., Allergenic tropomyosins have dissimilar structural stabilities despite having high amino acid sequence similarity. Tropomyosins are differentially degraded in the endolysosomal compartment of antigen‐presenting cells due to differences in their structural stability. Tropomyosin T‐cell cross‐reactivity, unlike IgE antibody cross‐reactivity, is dependent on structural stability rather than amino acid sequence similarity.

Published
2020
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48. A compendium answering 150 questions on COVID-19 and SARS-CoV-2

Author

Sebastian L. Johnston, Thomas Eiwegger, Ahmet Kursat Azkur, Jürgen Schwarze, Carmen Riggioni, Zuzana Diamant, Ioana Agache, Willem van de Veen, Milena Sokolowska, Mübeccel Akdis, Cezmi A. Akdis, Heimo Breiteneder, Luo Zhang, Josep M. Antó, María José Torres, Jean Bousquet, Rodrigo Jiménez-Saiz, Mattia Giovannini, Cristina Boccabella, Alessandra Arcolaci, Aspasia Karavelia, Menno C. van Zelm, Oliver Pfaar, Burcin Beken, Marek Sanak, Liam O'Mahony, Daniela Carvalho, Wytske Fokkens, Pasquale Comberiati, Marek Jutel, Kari C. Nadeau, Leticia De las Vecillas, Magna Alves-Correia, Ibon Eguiluz-Gracia, Farah Hannachi, Stefanie Eyerich, Robyn E O'Hehir, Ya dong Gao, Dilek Azkur, Beatriz Moya, De Yun Wang, Ludger Klimek, Consejo Superior de Investigaciones Científicas (España), Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Riggioni, Carmen [0000-0002-8745-0228], Comberiat, Pasquale [0000-0001-5209-9733], Giovannini, Mattia [0000-0001-9568-6882], Agache, Ioana [0000-0001-7994-364X], Akdis, Mubeccel [0000-0003-0554-9943], Alves-Correia, Magna [0000-0002-7676-5558], Antó, Josep M. [0000-0002-4736-8529], Azkur, Ahmet Kursat [0000-0002-5597-8917], Azkur, Dilek [0000-0002-4396-9087], Boccabella, Cristina [0000-0003-1942-8886], Breiteneder, Heimo [0000-0003-2022-8689], Carvalho, Daniela [0000-0002-0432-3339], Vecillas, Leticia de las [0000-0003-4969-5678], Diamant, Zuzana [0000-0003-0133-0100], Eguiluz-Gracia, Ibon [0000-0002-3774-931X], Eiwegger, Thomas [0000-0002-2914-7829], Fokkens, Wytske [0000-0003-4852-229X], Gao, Ya-dong [0000-0003-1251-7608], Nadeau, Kari C. [0000-0002-2146-2955], O'Mahony, Liam [0000-0003-4705-3583], Pfaar, Oliver [0000-0003-4374-9639], Sanak, Marek [0000-0001-7635-8103], Schwarze, Jürgen [0000-0002-6899-748X], Sokolowska, Milena [0000-0001-9710-6685], Torres Jaén, María José [0000-0001-5228-471X], Veen, Willem van de [0000-0001-9951-6688], Zelm, Menno C. van [0000-0003-4161-1919], Wang, De Yun [0000-0002-0909-2963], Zhang, Luo [0000-0002-0910-9884], Jiménez Saiz, Rodrigo [0000-0002-0606-3251], Akdis, Cezmi A. [0000-0001-8020-019X], Riggioni, Carmen, Comberiat, Pasquale, Giovannini, Mattia, Agache, Ioana, Akdis, Mubeccel, Alves-Correia, Magna, Antó, Josep M., Azkur, Ahmet Kursat, Azkur, Dilek, Boccabella, Cristina, Breiteneder, Heimo, Carvalho, Daniela, Vecillas, Leticia de las, Diamant, Zuzana, Eguiluz-Gracia, Ibon, Eiwegger, Thomas, Fokkens, Wytske, Gao, Ya-dong, Nadeau, Kari C., O'Mahony, Liam, Pfaar, Oliver, Sanak, Marek, Schwarze, Jürgen, Sokolowska, Milena, Torres Jaén, María José, Veen, Willem van de, Zelm, Menno C. van, Wang, De Yun, Zhang, Luo, Jiménez Saiz, Rodrigo, and Akdis, Cezmi A.

Subjects
0301 basic medicine, Allergy, AZITHROMYCIN, allergy, coronavirus disease 2019, COVID-19, SARS-CoV-2, severe acute respiratory syndrome–related coronavirus 2, Betacoronavirus, Coronavirus Infections, Humans, Hypersensitivity, Pandemics, Pneumonia, Viral, Disease, Review, SARS‐CoV‐2, 0302 clinical medicine, prevention, Pandemic, Epidemiology, Medicine, Immunology and Allergy, Viral, Coronavirus disease 2019, IMMUNE-RESPONSES, cytokine storm syndrome, severe acute respiratory syndrome‐related coronavirus 2, 1107 Immunology, epidemiology, SPIKE GLYCOPROTEIN, Life Sciences & Biomedicine, SARS-CORONAVIRUS, ANGIOTENSIN-CONVERTING ENZYME, medicine.medical_specialty, TRANSMISSION, Immunology, Reviews, Context (language use), 03 medical and health sciences, Severe acute respiratory syndrome–related coronavirus 2, EPIDEMIC, COVID‐19, LONGITUDINAL PROFILE, severe acute respiratory syndrome-related coronavirus 2, Intensive care medicine, Science & Technology, COVID-19, SARS-CoV-2, allergen immunotherapy, allergy, asthma, coronavirus disease 2019, cytokine storm syndrome, epidemiology, pandemic, prevention, severe acute respiratory syndrome-related coronavirus 2, business.industry, pandemic, Pneumonia, asthma, medicine.disease, KAWASAKI-LIKE DISEASE, Clinical trial, 030104 developmental biology, Clinical research, 030228 respiratory system, Severe acute respiratory syndrome-related coronavirus 2, allergen immunotherapy, business, Cytokine storm, ACUTE RESPIRATORY SYNDROME
Abstract

In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID‐19). This disease, caused by the severe acute respiratory syndrome–related coronavirus 2 (SARS‐CoV‐2), has developed into a pandemic. To date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. Unequivocally, the COVID‐19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence‐based medical advice on SARS‐CoV‐2 and COVID‐19. Although the majority of the patients show a very mild, self‐limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID‐19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thromboembolic complications, and multiorgan failure. The epidemiologic features of COVID‐19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID‐19–related topics should be based on more coordinated high‐quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS‐CoV‐2, COVID‐19, and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development, and epidemiology. A total of 150 questions were answered by experts in the field providing a comprehensive and practical overview of COVID‐19 and allergic disease., NHMRC Senior Research Fellowship, Grant/ Award Number: GNT1117687; Consejo Superior de Investigaciones Científicas, Grant/Award Number: IJCI-2016-27619; Instituto de Salud Carlos III, Grant/Award Number: JR19/0029

Published
2020

49. ARIA���EAACI statement on asthma and COVID���19 (June 2, 2020)

Author

Tari Haahtela, Victoria Cardona, Alvaro A. Cruz, Anna Bedbrook, Ken Ohta, Wienczyslawa Czarlewski, Nikos G. Papadopoulos, Marc Humbert, Menachem Rottem, Violeta Kvedariene, Omar S. Usmani, Eric D. Bateman, Helga Kraxner, Ludger Klimek, Hubert Blain, Thomas B. Casale, Mário Morais-Almeida, Aziz Sheikh, Joaquin Sastre, Piotr Kuna, Giovanni Rolla, Nataliya Ilina, Thomas Eiwegger, Seppo Koskinen, Tomas Chivato, Torsten Zuberbier, Nicola Scichilone, De Yun Wang, Luisa Brussino, Désirée Larenas-Linnemann, Manuel Soto-Martínez, Maciej Kupczyk, Karin Hoffmann-Sommergruber, Sharon Chinthrajah, Karl Christian Bergmann, M. Gotua, Sinthia Bosnic-Anticevich, Charlotte Suppli-Ulrik, Marek L. Kowalski, Mübeccel Akdis, Bilun Gemicioglu, Petr Panzner, Giovanni Viegi, Elisabete Nunes, Jürgen Schwarze, Sanna Toppila-Salmi, Ioanna Tsiligianni, Hui Du, Wytske Fokkens, Maria Teresa Ventura, Eckard Hamelmann, Paulo Augusto Moreira Camargos, Dmitry Kudlay, Mateo Bonini, Sian Williams, Mina Gaga, Louis-Philippe Boulet, Ignacio J. Ansotegui, Teresa To, Oliver Pfaar, Ioana Agache, Giorgio Walter Canonica, João Fonseca, Leyla Namazova, K. S. Bennoor, Elena Camelia Berghea, Ya-dong Gao, Roland Buhl, David M.G. Halpin, Gabrielle L. Onorato, Nhân Pham-Thi, Todor A. Popov, Mihaela Zidarn, Stefania Nicola, Branislava Milenkovic, Robyn E O'Hehir, Kari C. Nadeau, Juan Carlos Ivancevich, Luís Taborda-Barata, Florin Mihaltan, Amir Hamzah Abdul Latiff, Rafael Stelmach, Marek Jutel, Frederico S. Regateiro, B. Pigearias, Theodor Vontetsianos, Ruby Pawankar, Mohammad R. Masjedi, Renaud Louis, Musa Khaitov, Manuel E. Soto-Quiros, Lan T. Le, H. Neffen, Yousser Mohammad, Yoshitaka Okamoto, Fanny W.S. Ko, Yehia El-Gamal, Edward F. Knol, Gary W.K. Wong, Guy Joos, Gianni Passalacqua, Jean Bousquet, Paul M. O'Byrne, Arunas Valiulis, Cezmi A. Akdis, George Christoff, Bolesław Samoliński, Claus Bachert, Vincenzo Patella, Josep M. Antó, Arzu Yorgancioglu, Michael Levin, Liam O'Mahony, Mario E. Zernotti, Erik Melén, Joaquim Mullol, Peter Valentin Tomazic, Stefano Del Giacco, Francesca Puggioni, Milan Sova, Bruce Kirenga, UAM. Departamento de Medicina, Ear, Nose and Throat, AII - Inflammatory diseases, Bousquet J., Jutel M., Akdis C.A., Klimek L., Pfaar O., Nadeau K.C., Eiwegger T., Bedbrook A., Ansotegui I.J., Anto J.M., Bachert C., Bateman E.D., Bennoor K.S., Berghea E.C., Bergmann K.-C., Blain H., Bonini M., Bosnic-Anticevich S., Boulet L.-P., Brussino L., Buhl R., Camargos P., Canonica G.W., Cardona V., Casale T., Chinthrajah S., Akdis M., Chivato T., Christoff G., Cruz A.A., Czarlewski W., Del Giacco S., Du H., El-Gamal Y., Fokkens W.J., Fonseca J.A., Gao Y., Gaga M., Gemicioglu B., Gotua M., Haahtela T., Halpin D., Hamelmann E., Hoffmann-Sommergruber K., Humbert M., Ilina N., Ivancevich J.-C., Joos G., Khaitov M., Kirenga B., Knol E.F., Ko F.W., Koskinen S., Kowalski M.L., Kraxner H., Kudlay D., Kuna P., Kupczyk M., Kvedariene V., Abdul Latiff A.H., Le L.T., Levin M., Larenas-Linnemann D., Louis R., Masjedi M.R., Melen E., Mihaltan F., Milenkovic B., Mohammad Y., Morais-Almeida M., Mullol J., Namazova L., Neffen H., Nunes E., O'Byrne P., O'Hehir R., O'Mahony L., Ohta K., Okamoto Y., Onorato G.L., Panzner P., Papadopoulos N.G., Passalacqua G., Patella V., Pawankar R., Pham-Thi N., Pigearias B., Popov T.A., Puggioni F., Regateiro F.S., Rolla G., Rottem M., Samolinski B., Sastre J., Schwarze J., Sheikh A., Scichilone N., Soto-Quiros M., Soto-Martinez M., Sova M., Nicola S., Stelmach R., Suppli-Ulrik C., Taborda-Barata L., To T., Tomazic P.-V., Toppila-Salmi S., Tsiligianni I., Usmani O., Valiulis A., Ventura M.T., Viegi G., Vontetsianos T., Wang D.Y., Williams S., Wong G.W.K., Yorgancioglu A., Zernotti M., Zidarn M., Zuberbier T., and Agache I.

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Allergy, Statement (logic), Medicina, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, Immunology, Settore MED/10 - Malattie Dell'Apparato Respiratorio, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, astma, Medicine and Health Sciences, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, Letters to the Editor, Letter to the Editor, udc:616.2, Asthma, Coronavirus, Science & Technology, business.industry, SARS-CoV-2, virus diseases, COVID-19, asthma, medicine.disease, Virology, 3. Good health, 030228 respiratory system, covid-19, 1107 Immunology, Angiotensin-Converting Enzyme 2, business, ARIA-EAACI, Life Sciences & Biomedicine, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
Abstract

Artículo con numerosos autores sólo se mencionan el primero y el de la UAM, Open access funding enabled and organized by Projekt DEAL

Published
2020
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50. Influenza‐specific IgG1+ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency

Author

Philip Mark Hogarth, Gemma E. Hartley, Emily S.J. Edwards, Katie L. Flanagan, Menno C. van Zelm, Robert G Stirling, Paul U. Cameron, Magdalena Plebanski, Samar Ojaimi, Robyn E O'Hehir, and Julian J. Bosco

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, Immunology, predominantly antibody deficiency, Hemagglutinin (influenza), Serology, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Immune system, Immunophenotyping, Immunology and Allergy, Medicine, Memory B cell, General Nursing, biology, medicine.diagnostic_test, business.industry, Original Articles, vaccination, Vaccination, 030104 developmental biology, biology.protein, Original Article, antigen‐specific memory B cells, Antibody, business, influenza, lcsh:RC581-607, 030215 immunology
Abstract

Background Annual influenza vaccination is recommended to all individuals over 6 months of age, including predominantly antibody deficiency (PAD) patients. Vaccination responses are typically evaluated by serology, and because PAD patients are by definition impaired in generating IgG and receive immunoglobulin replacement therapy (IgRT), it remains unclear whether they can mount an antigen‐specific response. Objective To quantify and characterise the antigen‐specific memory B (Bmem) cell compartment in healthy controls and PAD patients following an influenza booster vaccination. Methods Recombinant hemagglutinin (HA) from the A/Michigan/2015 H1N1 (AM15) strain with an AviTag was generated in a mammalian cell line, and following targeted biotinylation, was tetramerised with BUV395 or BUV737 streptavidin conjugates. Multicolour flow cytometry was applied on blood samples before and 28 days after booster influenza vaccination in 16 healthy controls and five PAD patients with circulating Bmem cells. Results Recombinant HA tetramers were specifically recognised by 0.5–1% of B cells in previously vaccinated healthy adults. HA‐specific Bmem cell numbers were significantly increased following booster vaccination and predominantly expressed IgG1. Similarly, PAD patients carried HA‐specific Bmem cells, predominantly expressing IgG1. However, these numbers were lower than in controls and did not increase following booster vaccination. Conclusion We have successfully identified AM15‐specific Bmem cells in healthy controls and PAD patients. The presence of antigen‐specific Bmem cells could offer an additional diagnostic tool to aid in the clinical diagnosis of PAD. Furthermore, alterations in the number or immunophenotype of HA‐specific Bmem cells post‐booster vaccination could assist in the evaluation of immune responses in individuals receiving IgRT., We here developed an extensive flowcytometry panel to examine influenza‐specific memory B cells using fluorescently labeled recombinant haemagglutinin (HA) tetramers. Influenza‐specific memory B cells were predominantly IgG1+, and these were increased following booster vaccination in healthy controls, but not in patients with predominantly antibody deficiency.

Published
2020

Catalog

Books, media, physical & digital resources
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