Medical Journal Review
July 2021
WAO Reviews – Editors’ Choice
Articles are selected for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases by Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD - FACAAI - FAAAAI, WAO Reviews Editor.
The important role of non-covalent drug-protein interactions in drug hypersensitivity reactions
Pichler WJ
Allergy 2021; Published online ahead of print (26 May)
DOI: https://doi.org/10.1111/all.14962
Drug hypersensitivity reactions (DHR) are heterogeneous and unusual immune reactions, with disparate clinical presentations. Accumulating evidence indicates that certain non-covalent drug-protein interactions are able to elicit exclusively effector functions of antibody reactions or complete T-cell reactions.
In this review, Pichler discusses three key interactions:
- mimicry; whereby soluble, non-covalent drug-protein complexes (“fake antigens”) mimic covalent drug-protein adducts,
- increased antibody affinity; for example, in quinine-type immune thrombocytopenia where the drug gets trapped between antibody and membrane-bound glycoprotein, and
- p-i-stimulation; where naïve and memory T cells are activated by direct binding of drugs to the human leukocyte antigen and/or T-cell receptors.
This transient drug-immune receptor interaction then initiates a polyclonal T-cell response with mild-to-severe DHR symptoms with potential complications including viral reactivation, autoimmunity, and multiple drug hypersensitivity.
Allergen immunotherapy in pediatric respiratory allergy
Doroudchi A, Imam K, and Garcia Lloret, MI
Current Treatment Options in Allergy 2021;8:147-160
DOI: https://doi.org/10.1007/s40521-021-00280-4
When considering treatment for allergically mediated rhinitis or asthma, options include pharmacotherapy, which may only partially treat symptoms and require long-term use. On the other hand, allergen immunotherapy (AIT) can alter the underlying disease process and potentially offer a cure. In this review article, the authors explore the merits of AIT with particular emphasis on its efficacy and safety in pediatric patients. The authors also discuss the challenges for AIT implementation and present an overview of current research that aims at improving its applicability for the treatment of allergic diseases. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are both safe and efficacious treatment options in children with allergic rhinitis and allergic asthma. Additionally, AIT has efficacy in preventing the development of asthma in children. Although there are clear advantages with AIT, there are also challenges to overcome to optimize treatment. Solutions include improved diagnostics with pre-treatment biomarkers and molecular multiplex assays, biomarkers for prediction of response (e.g., basophil activation markers), improved allergen immunogenicity with the use of recombinant AIT, adjuvants, and allergoids, and lastly improved safety with the concurrent use of omalizumab.
Management of anaphylaxis during the SARS-CoV-2 pandemic
Brar KK, Harizaj A, Nowak-Wegrzyn A
Current Treatment Options in Allergy 2021;8:88-96
DOI: https://doi.org/10.1007/s40521-021-00284-0
In this review, Brar and colleagues identify a treatment strategy for anaphylaxis that balances the risks versus benefits of emergency department (ED) versus home management during this unprecedented time of the SARS-CoV-2 pandemic. Physicians and patients have had to adapt new approaches to medical care during the SARS-CoV-2 pandemic due to restricted access to health care facilities. The authors suggest that physicians should utilize telemedicine during this time to engage in shared decision-making with patients and their families to devise an anaphylaxis plan of management that emphasizes home care when symptoms are mild with an exception for ED care if a patient has had severe, near-fatal anaphylaxis episodes in the past. Furthermore, they recommend that previous anaphylaxis recommendations should remain in place despite the pandemic, including prompt use of epinephrine when needed, avoidance of known allergens, training of patients and their caregivers, and carrying of epinephrine autoinjector devices at all times to remain prepared in the event of an anaphylaxis episode.
Innate immune regulation of dermatitis
Abreu D and Kim BS
Immunology & Allergy Clinics 2021;41(3):347-359
DOI: https://doi.org/10.1016/j.iac.2021.04.011
Over the past two decades, the evolving therapeutic landscape of inflammatory cutaneous disorders has been largely driven by scientific advances in the understanding of skin immunology. In particular, seminal discoveries of the mechanisms underlying neuroimmune crosstalk have not only identified novel targets for medical intervention, but also provided an understanding for reasons of lack of efficacy associated with previous treatments. The discovery of the MRGPRB2/X2–mast cell signaling axis, for example, has shed new light on the shortcomings of IgE and histamine blockade in treating pruritic disorders such as allergic contact dermatitis, while simultaneously opening new lines of inquiry into the potential contribution of MRGPRB2/X2 biology in the context of chronic spontaneous urticaria, and contact urticaria.
Integrated omics endotyping of infants with respiratory syncytial virus bronchiolitis and risk of childhood asthma
Raita Y, Pérez-Losada M, Freishtat RJ et al
Nature Communications 2021;12(1):3601
DOI: https://doi.org/10.1038/s41467-021-23859-6
Respiratory syncytial virus (RSV) bronchiolitis is a leading cause of hospitalization in U.S. infants, and may be a major risk factor for asthma development. While emerging evidence suggests clinical heterogeneity within RSV bronchiolitis, little is known about its biologically distinct endotypes. In this communication, the authors present the integrated clinical, virus, airway microbiome (species-level), transcriptome, and metabolome data of 221 infants hospitalized with RSV bronchiolitis in a multicenter prospective cohort study.
They identified four biologically- and clinically-meaningful endotypes:
- clinicalclassicmicrobiomeM. nonliquefaciensinflammationIFNintermediate,
- clinicalatopicmicrobiomeS. pneumoniae/M. catarrhalisinflammationIFN-high,
- clinicalseveremicrobiomemixedinflammationIFN-low, and
- clinicalnon-atopicmicrobiomeM.catarrhalisinflammationIL-6.
It should be noted that compared with endotype A infants, endotype B infants—who are characterized by a high proportion of IgE sensitization and rhinovirus coinfection, S. pneumoniae/M. catarrhalis codominance, and high IFN-α and -γ response—had a significantly higher risk for developing asthma (9% vs. 38%; OR, 6.00: 95%CI, 2.08–21.9; P = 0.002). The authors conclude that their findings provide an evidence base for the early identification of high-risk children during a critical period in their airway development
