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June 2021

Airway smooth muscle pathophysiology in asthma

Blanca Camoretti-Mercado, PhD, MBAIS and Richard F. Lockey, MD


The airway smooth muscle (ASM) cell plays a central role in the pathogenesis of asthma and constitutes an important target for treatment. These cells control muscle tone and thus regulate the opening of the airway lumen and air passage. Evidence indicates that ASM cells participate in the airway hyperresponsiveness as well as the inflammatory and remodeling processes observed in asthmatic subjects. Therapeutic approaches require a comprehensive understanding of the structure and function of the ASM in both the normal and disease states. This review updates current knowledge about ASM and its effects on airway narrowing, remodeling, and inflammation in asthma. (J Allergy Clin Immunol 2021;147:1983-95.)

Biology and dynamics of B cells in the context of IgE-mediated food allergy

Pattraporn Satitsuksanoa, Monique Daanje, Mübeccel Akdis, Scott D. Boyd & Willem van de Veen



An increasing number of people suffer from IgE-mediated food allergies. The immunological mechanisms that cause IgE-mediated food allergy have been extensively studied. B cells play a key role in the development of IgE-mediated food allergies through the production of allergen-specific antibodies. While this particular function of B cells has been known for many years, we still do not fully understand the mechanisms that regulate the induction and maintenance of allergen-specific IgE production. It is still not fully understood where in the body IgE class switch recombination of food allergen-specific B cells occurs, and what processes are involved in the immunological memory of allergen-specific IgE responses. B cells can also contribute to the regulation of allergen-specific immune responses through other mechanisms such as antigen presentation and cytokine production. Recent technological advances have enabled highly detailed analysis of small subsets of B cells down to the single-cell level. In this review, we provide an overview of the current knowledge on the biology of B cells in relation to IgE-mediated food allergies.

COVID-19 Vaccination in Patients with Reported Allergic Reactions: Updated Evidence and Suggested Approach

Aleena Banerji, MD, Anna R. Wolfson, MD, Paige G. Wickner, MD, MPH, Amelia S. Cogan, MPH, Aubree E. McMahon, BA, Rebecca Saff, MD, PhD, Lacey B. Robinson, MD, MPH Elizabeth Phillips, MD and Kimberly G. Blumenthal, MD, MSc

COVID‑19 vaccine testing & administration guidance for allergists/immunologists from the Canadian Society of Allergy and Clinical Immunology (CSACI)

Timothy K. Vander Leek, Edmond S. Chan, Lori Connors, Beata Derfalvi, Anne K. Ellis, Julia E. M. Upton and Elissa M. Abrams


Background: Safe and effective vaccines provide the first hope for mitigating the devastating health and economic impacts resulting from coronavirus disease 2019 (COVID-19) and related public health orders. Recent case reports of reactions to COVID-19 vaccines have raised questions about their safety for use in individuals with allergies and those who are immunocompromised. In this document, we aim to address these concerns and provide guidance for allergists/immunologists.
Methods: Scoping review of the literature regarding COVID-19 vaccination, adverse or allergic reactions, and immunocompromise from PubMed over the term of December 2020 to present date. We filtered our search with the terms “human” and “English” and limited the search to the relevant subject age range with the term “adult.” Reports resulting from these searches and relevant references cited in those reports were reviewed and cited on the basis of their relevance.
Results: Assessment by an allergist is warranted in any individual with a suspected allergy to a COVID-19 vaccine or any of its components. Assessment by an allergist is NOT required for individuals with a history of unrelated allergies, including to allergies to foods, drugs, insect venom or environmental allergens. COVID-19 vaccines should be offered to immunocompromised patients if the benefit is deemed to outweigh any potential risks of vaccination.
Interpretation: This review provides the first Canadian guidance regarding assessment of an adolescent and adult with a suspected allergy to one of the COVID-19 vaccines currently available, or any of their known allergenic components, and for patients who are immunocompromised who require vaccination for COVID-19. As information is updated this guidance will be updated accordingly.

EAACI statement on the diagnosis, management and prevention of severe allergic reactions to COVID-19 vaccines

Milena Sokolowska, Thomas Eiwegger, Markus Ollert, Maria J. Torres, Domingo Barber, Stefano Del Giacco, Marek Jutel, Kari C. Nadeau, Oscar Palomares, Ronald L. Rabin, Carmen Riggioni, Stefan Vieths, Ioana Agache and Mohamed H. Shamji


The first approved COVID-19 vaccines include Pfizer/BioNTech BNT162B2, Moderna mRNA-1273 and AstraZeneca recombinant adenoviral ChAdOx1-S. Soon after approval, severe allergic reactions to the mRNA-based vaccines that resolved after treatment were reported. Regulatory agencies from the European Union, Unites States and the United Kingdom agree that vaccinations are contraindicated only when there is an allergy to one of the vaccine components or if there was a severe allergic reaction to the first dose. This position paper of the European Academy of Allergy and Clinical Immunology (EAACI) agrees with these recommendations and clarifies that there is no contraindication to administer these vaccines to allergic patients who do not have a history of an allergic reaction to any of the vaccine components. Importantly, as is the case for any medication, anaphylaxis may occur after vaccination in the absence of a history of allergic disease. Therefore, we provide a simplified algorithm of prevention, diagnosis and treatment of severe allergic reactions and a list of recommended medications and equipment for vaccine centres. We also describe potentially allergenic/ immunogenic components of the approved vaccines and propose a workup to identify the responsible allergen. Close collaboration between academia, regulatory agencies and vaccine producers will facilitate approaches for patients at risks, such as incremental dosing of the second injection or desensitization. Finally, we identify unmet research needs and propose a concerted international roadmap towards precision diagnosis and management to minimize the risk of allergic reactions to COVID-19 vaccines and to facilitate their broader and safer use.

Memory-type pathogenic TH2 cells and ILC2s in type 2 allergic inflammation

Kiyoshi Hirahara, MD, PhD, Ami Aoki, MD, PhD, Masahiro Kiuchi, DVM, PhD and Toshinori Nakayama, MD, PhD

Potential mechanisms of anaphylaxis to COVID-19 mRNA vaccines

Kimberly A. Risma, MD, PhD, Kathryn M. Edwards, MD, Donna S. Hummell, MD, Frederic F. Little, MD, Allison E. Norton, MD, Amy Stallings, MD, Robert A. Wood, MD and Joshua D. Milner, MD


Anaphylaxis to vaccines is historically a rare event. The coronavirus disease 2019 pandemic drove the need for rapid vaccine production applying a novel antigen delivery system: messenger RNA vaccines packaged in lipid nanoparticles. Unexpectedly, public vaccine administration led to a small number of severe allergic reactions, with resultant substantial public concern, especially within atopic individuals. We reviewed the constituents of the messenger RNA lipid nanoparticle vaccine and considered several contributors to these reactions: (1) contact system activation by nucleic acid, (2) complement recognition of the vaccine-activating allergic effector cells, (3) preexisting antibody recognition of polyethylene glycol, a lipid nanoparticle surface hydrophilic polymer, and (4) direct mast cell activation, coupled with potential genetic or environmental predispositions to hypersensitivity. Unfortunately, measurement of anti– polyethylene glycol antibodies in vitro is not clinically available, and the predictive value of skin testing to polyethylene glycol components as a coronavirus disease 2019 messenger RNA vaccine-specific anaphylaxis marker is unknown. Even less is known regarding the applicability of vaccine use for testing (in vitro/vivo) to ascertain pathogenesis or predict reactivity risk. Expedient and thorough research-based evaluation of patients who have suffered anaphylactic vaccine reactions and prospective clinical trials in putative at-risk individuals are needed to address these concerns during a public health crisis. (J Allergy Clin Immunol 2021;147:2075-82.)

Single-cell molecular profiling provides a high-resolution map of basophil and mast cell development

Fiona K. Hamey, Winnie W.Y. Lau, Iwo Kucinski, Xiaonan Wang, Evangelia Diamanti, Nicola K. Wilson, Berthold Göttgens and Joakim S. Dahlin


Background: Basophils and mast cells contribute to the development of allergic reactions. Whereas these mature effector cells are extensively studied, the differentiation trajectories from hematopoietic progenitors to basophils and mast cells are largely uncharted at the single-cell level.
Methods: We performed multicolor flow cytometry, high-coverage single-cell RNA sequencing analyses, and cell fate assays to chart basophil and mast cell differentiation at single-cell resolution in mouse.
Results: Analysis of flow cytometry data reconstructed a detailed map of basophil and mast cell differentiation, including a bifurcation of progenitors into two specific trajectories. Molecular profiling and pseudotime ordering of the single cells revealed gene expression changes during differentiation. Cell fate assays showed that multicolor flow cytometry and transcriptional profiling successfully predict the bipotent phenotype of a previously uncharacterized population of peritoneal basophil-mast cell progenitors.
Conclusions: A combination of molecular and functional profiling of bone marrow and peritoneal cells provided a detailed road map of basophil and mast cell development. An interactive web resource was created to enable the wider research community to explore the expression dynamics for any gene of interest.

Vaccines and allergic reactions: The past, the current COVID-19 pandemic, and future perspectives

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


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.

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