Medical Journal Review
June 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.
One hundred ten years of allergen immunotherapy: A broad look into the future
Pfaar O, Creticos PS, Kleine-Tebbe J et al
Journal of Allergy and Clinical Immunology: In Practice 2021;9(5):1791-1803
DOI: https://doi.org/10.1016/j.jaip.2020.12.067
This comprehensive review explores innovative approaches in allergen immunotherapy (AIT), focusing on promising candidates for the future. The authors specifically spotlight biologicals, allergen-derived peptides, recombinant allergens, “Toll”-like receptor agonists and other adjuvants, as well as novel application routes being developed for future AIT.
Invited review: The role of allergen-specific IgE, IgG and IgA in allergic disease
Shamji MH, Valenta R, Jardetzky T et al
Allergy 2021; Published online ahead of print (17 May)
DOI: https://doi.org/10.1111/all.14908
In this review, Shamji et al examine the complex interplay between allergen specific IgE, IgG and IgA and the corresponding cell receptors associated with allergic disease, focusing on their relevance in diagnosis, treatment, and prevention of allergy.
Genetic effects of allergen-specific IgE levels on exhaled nitric oxide in schoolchildren with asthma: The STOPPA twin study
Hedman AM, Kuja-Halkola R, Örtqvist AK et al
Pediatric Allergy and Immunology 2021;32(4):709-719
DOI: https://doi.org/10.1111/pai.13438
This study by Hedman and colleagues was a population-based, cross-sectional twin study which enrolled 612 monozygotic (MZ) and same-sex dizygotic (DZ) schoolchildren and utilized structural equation modelling to separate the covariance between asthma and exhaled nitric oxide into genetic and/or environmental effects, taking allergen-specific IgE level and blood eosinophil count into account while controlling for confounding factors. They found that cross-twin/cross-trait correlations had a higher magnitude in the MZ twins than in the DZ twins, indicating that genes affect the association. The likelihood ratio test for model fitting resulted in the AE model (ie, additive genetic effects, A, and non-shared environmental effects) as the most parsimonious. A majority (73%), of the phenotypic correlation between asthma and exhaled nitric oxide, r = .19 (0.05-0.33), was attributable to genetic effects which mainly was due to the allergen specific IgE level. Overall, this study indicates that the association between asthma and exhaled nitric oxide in children is to a large extent explained by genetics via allergen-specific IgE level and not blood eosinophils.
Probiotic potential of lactobacillus species in allergic rhinitis
Steiner NC, Lorentz A
International Archives of Allergy and Immunology 2021; Published online 21 April
DOI: https://doi.org/10.1159/000515352
Probiotic bacteria, such as Lactobacillus species, have shown anti-allergic effects in various mouse and human studies. Prior research has demonstrated that administration of some Lactobacillus species resulted in nasal and ocular symptom relief and improvement of quality of life in children and adults suffering from rhinitis. Further studies have shown changes in cytokine profiles, such as elevated Th1 and decreased Th2 cytokines, reduced allergy-related immunoglobulins and cell immigration have been found in both human and murine studies. Positive effects including reduction in activity limitations, fewer rhinitis episodes, and longer periods free from asthma or rhinitis have also been described following oral administration of Lactobacillus bacteria. However, it is still unclear how these bacteria lead to changes in the immune system and inhibit the development of allergies or relieve their symptoms. This review gives an overview of current studies and explores the usage of probiotic Lactobacillus strains in AR.
High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages
Hoepel W, Chen H-J, Geyer CE et al
Science Translational Medicine 2021;13(596):eabf8654
DOI: https://doi.org/10.1126/scitranslmed.abf8654
Patients diagnosed with coronavirus disease 2019 (COVID-19) become critically ill primarily around the time of activation of the adaptive immune response. In this article, the authors provide evidence that antibodies play a role in the worsening of disease at the time of seroconversion. Specifically, they show that early phase severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific IgG in serum of critically ill COVID-19 patients induces excessive inflammatory responses by human alveolar macrophages. Excessive inflammatory response is dependent on two antibody features that are specific for patients with severe COVID-19: first, inflammation is driven by high titers of anti-spike IgG, a hallmark of severe disease; second, the anti-spike IgG from patients with severe COVID-19 is intrinsically more pro-inflammatory because of different glycosylation, particularly low fucosylation, of the antibody Fc tail. Notably, low fucosylation of anti-spike IgG normalized within a few weeks after initial infection with SARS-CoV-2, indicating that the increased antibody-dependent inflammation mainly occurs at the time of seroconversion. The authors identified Fcγ Receptor (FcγR) IIa and FcγRIII as the two primary IgG receptors that are responsible for the induction of key COVID-19-associated cytokines such as interleukin-6 and tumor necrosis factor. In addition, they demonstrated that anti-spike IgG-activated human macrophages can subsequently break pulmonary endothelial barrier integrity and induce microvascular thrombosis in vitro. Finally, they found that the inflammatory response induced by anti-spike IgG can be specifically counteracted by fostamatinib, an FDA- and EMA-approved therapeutic small molecule inhibitor of Syk kinase.
