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December 2021

Advances and highlights in biomarkers of allergic diseases

Ogulur I, Pat Y, Ardicli O, et al.

Abstract: During the past years, there has been a global outbreak of allergic diseases, presenting a considerable medical and socioeconomical burden. A large fraction of allergic diseases is characterized by a type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, eosinophils, mast cells, and M2 macrophages. Biomarkers are valuable parameters for precision medicine as they provide information on the disease endotypes, clusters, precision diagnoses, identification of therapeutic targets, and monitoring of treatment efficacies. The availability of powerful omics technologiestogether with integrated data analysis and network-based approaches can help the identification of clinically useful biomarkers. These biomarkers need to be accurately quantified using robust and reproducible methods, such as reliable and point-of-care systems. Ideally, samples should be collected using quick, cost-efficient and noninvasive methods. In recent years, a plethora of research has been directed toward finding novel biomarkers of allergic diseases. Promising biomarkers of type 2 allergic diseases include sputum eosinophils, serum periostin and exhaled nitric oxide. Several other biomarkers, such as pro-inflammatory mediators, miRNAs, eicosanoid molecules, epithelial barrier integrity, and microbiota changes are useful for diagnosis and monitoring of allergic diseases and can be quantified in serum, body fluids and exhaled air. Herein, we review recent studies on biomarkers for the diagnosis and treatment of asthma, chronic urticaria, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, food allergies, anaphylaxis, drug hypersensitivity and allergen immunotherapy. In addition, we discuss COVID-19 and allergic diseases within the perspective of biomarkers and recommendations on the management of allergic and asthmatic patients during the COVID-19 pandemic.


Molecular allergology and its impact in specific allergy diagnosis and therapy

Barber D, Diaz-Perales A, Escribese MM, et al.

Abstract: Progressive knowledge of allergenic structures resulted in a broad availability of allergenic molecules for diagnosis. Component-resolved diagnosis allowed a better understanding of patient sensitization patterns, facilitating allergen immunotherapy decisions. In parallel to the discovery of allergenic molecules, there was a progressive development of a regulation framework that affected both in vitro diagnostics and Allergen Immunotherapy products. With a progressive understanding of underlying mechanisms associated to Allergen immunotherapy and an increasing experience of application of molecular diagnosis in daily life, we focus in analyzing the evidences of the value provided by molecular allergology in daily clinical practice, with a focus on Allergen Immunotherapy decisions.


Impact of inhaled pollutants on response to viral infection in controlled exposures

Rebuli M, Brocke S, Jaspers I

Introduction: Air pollutants are a major source of increased risk of disease, hospitalization, morbidity, and mortality worldwide. The respiratory tract is a primary target of potential concurrent exposure to both inhaled pollutants and pathogens, including viruses. Although there are various associative studies linking adverse outcomes to co- or subsequent exposures to inhaled pollutants and viruses, knowledge about causal linkages and mechanisms by which pollutant exposure may alter human respiratory responses to viral infection is more limited. In this article, we review what is known about the impact of pollutant exposure on antiviral host defense responses and describe potential mechanisms by which pollutants can alter the viral infection cycle. This review focuses on evidence from human observational and controlled exposure, ex vivo, and in vitro studies. Overall, there are a myriad of points throughout the viral infection cycle that inhaled pollutants can alter to modulate appropriate host defense responses. These alterations may contribute to observed increases in rates of viral infection and associated morbidity and mortality in areas of the world with high ambient pollution levels or in people using tobacco products. Although the understanding of mechanisms of interaction is advancing through controlled in vivo and in vitro exposure models, more studies are needed because emerging infectious pathogens, such as severe acute respiratory syndrome coronavirus 2, present a significant threat to public health. (J Allergy Clin Immunol 2021;148:1420-9.)


Immunological resilience and biodiversity for prevention of allergic diseases and asthma

Haahtela T, Alenius H, Lehtimäki J, et al.

Abstract: Increase of allergic conditions has occurred at the same pace with the Great Acceleration, which stands for the rapid growth rate of human activities upon earth from 1950s. Changes of environment and lifestyle along with escalating urbanization are acknowledged as the main underlying causes. Secondary (tertiary) prevention for better disease control has advanced considerably with innovations for oral immunotherapy and effective treatment of inflammation with corticosteroids, calcineurin inhibitors, and biological medications. Patients are less disabled than before. However, primary prevention has remained a dilemma. Factors predicting allergy and asthma risk have proven complex: Risk factors increase the risk, while protective factors counteract them. Interaction of human body with environmental biodiversity with micro-organisms and biogenic compounds as well as the central role of epigenetic adaptation in immune homeostasis have given new insight. Allergic diseases are good indicators of the twisted relation to environment. In various non-communicable diseases, the protective mode of the immune system indicates low-grade inflammation without apparent cause. Giving microbes, pro-and prebiotics, has shown some promise in prevention and treatment. The real-world public health programme in Finland (2008–2018) emphasized nature relatedness and protective factors for immunological resilience, instead of avoidance. The nationwide action mitigated the allergy burden, but in the lack of controls, primary preventive effect remains to be proven. The first results of controlled biodiversity interventions are promising. In the fast urbanizing world, new approaches are called for allergy prevention, which also has a major cost saving potential.


Immunologic memory to SARS-CoV-2 in convalescent COVID-19 patients at 1 year postinfection

Hou H, Zhang Y, Tang G, et al.

Background: Understanding the complexities of immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to gain insights into the durability of protective immunity against reinfection.

Objective: We sought to evaluate the immune memory to SARSCoV-2 in convalescent patients with longer follow-up time.

Methods: SARS CoV-2–specific humoral and cellular responses were assessed in convalescent patients with coronavirus disease 2019 (COVID-19) at 1 year postinfection.

Results: A total of 78 convalescent patients with COVID-19 (26 moderate, 43 severe, and 9 critical) were recruited after 1 year of recovery. The positive rates of both anti–receptor-binding domain and antinucleocapsid antibodies were 100%, whereas we did not observe a statistical difference in antibody levels among different severity groups. Accordingly, the prevalence of neutralizing antibodies (nAbs) reached 93.59% in convalescent patients. Although nAb titers displayed an increasing trend in convalescent patients with increased severity, the difference failed to achieve statistical significance. Notably, there was a significant correlation between nAb titers and anti–receptorbinding domain levels. Interestingly, SARS-CoV-2–specific T cells could be robustly maintained in convalescent patients, and their number was positively correlated with both nAb titers and anti–receptor-binding domain levels. Amplified SARS-CoV-2–specific CD41 T cells mainly produced a single cytokine, accompanying with increased expression of exhaustion markers including PD-1, Tim-3, TIGIT, CTLA-4, and CD39, while the proportion of multifunctional cells was low.

Conclusions: Robust SARS-CoV-2–specific humoral and cellular responses are maintained in convalescent patients with COVID-19 at 1 year postinfection. However, the dysfunction of SARS-CoV-2–specific CD41 T cells supports the notion that vaccination is needed in convalescent patients for preventing reinfection. (J Allergy Clin Immunol 2021;148:1481-92.)


Global patterns in anaphylaxis due to specific foods: A systematic review

Conrado A B, Patel N, Turner P

Background: There are increasing global data relating to prevalence of food allergy and food-induced anaphylaxis; however, this is often based on surrogate measures of sensitization rather than objective symptoms at food challenge. In terms of protecting food-allergic consumers from reactions, to our knowledge, there has been no global survey assessing geographic differences in the proportion of anaphylaxis triggered by specific foods.

Objective: We sought to identify common triggers for foodinduced anaphylaxis and how these vary from country to country.

Methods: Systematic review of relevant reports published between January 2010 and November 2020. Results were reported following PRISMA guidelines. Publications were screened and data extracted by 2 independent reviewers, and the risk of bias was assessed.

Results: Sixty-five studies (encompassing 41 countries and all 6 regions as defined by the Food and Agriculture Organization of the United Nations) were included. Significant regional variations in the most common triggers of food anaphylaxis were seen; however, in general, there was good agreement between local legislative requirements for allergen disclosure and the most common allergens for each region or nation.

Conclusions: Local legislation for allergen disclosure generally reflects those allergens commonly responsible for food anaphylaxis. Cow’s milk and crustaceans appear to cause a higher proportion of anaphylaxis compared to peanut in some regions. (J Allergy Clin Immunol 2021;148:1515-25.)


The role of allergen-specific IgE, IgG and IgA in allergic disease

Shamji MH, Valenta R, Jardetzky T, et al.

Abstract: Immunoglobulin E (IgE)-mediated allergy is the most common hypersensitivity disease affecting more than 30% of the population. Exposure to even minute quantities of allergens can lead to the production of IgE antibodies in atopic individuals. This is termed allergic sensitization, which occurs mainly in early childhood. Allergen-specific IgE then binds to the high (FcεRI) and low-affinity receptors (FcεRII, also called CD23) for IgE on effector cells and antigen-presenting cells. Subsequent and repeated allergen exposure increases allergen-specific IgE levels and, by receptor cross-linking, triggers immediate release of inflammatory mediators from mast cells and basophils whereas IgE facilitated allergen presentation perpetuates T cell–mediated allergic inflammation. Due to engagement of receptors which are highly selective for IgE, even tiny amounts of allergens can induce massive inflammation. Naturally occurring allergen-specific IgG and IgA antibodies usually recognize different epitopes on allergens compared with IgE and do not efficiently interfere with allergen-induced inflammation. However, IgG and IgA antibodies to these important IgE epitopes can be induced by allergen-specific immunotherapy or by passive immunization. These will lead to competition with IgE for binding with the allergen and prevent allergic responses. Similarly, anti-IgE treatment does the same by preventing IgE from binding to its receptor on mast cells and basophils. Here, we review the complex interplay of allergen-specific IgE, IgG and IgA and the corresponding cell receptors in allergic diseases and its relevance for diagnosis, treatment and prevention of allergy.


The curious history behind a biologic-enriched cat food: Hyperimmune avian IgY as a means of oral adoptive passive immunization

Steinberg J

Introduction: Multiple potential therapeutic mechanisms of allergen immunotherapy have been postulated; however, its clinical benefit appears to correlate best with serum concentrations of allergenspecific neutralizing polyclonal IgG41. The central role of IgG4 underlying much of the clinical response to allergen immunotherapy via allergen neutralization has been strengthened by a study of passively immunizing patients with cat allergy with monoclonal anti–Felinus domesticus 1 (Fel d 1) IgG4, which has induced rapid clinical benefit in cat dander challenge studies.2 Neutralizing Fel d 1 with passive immunization by using anti–Fel d 1 antibody is thus a potential therapeutic for patients with cat dander allergy. In February 2020, Nestle Purina, Inc, released a new line of cat food with implied benefit for persons with cat allergy. This cat food is prepared by admixing regular cat food with polyclonal IgY targeting the predominant cat allergen Fel d 1. The IgY is derived from egg yolks laid by hens hyperimmunized against recombinant Fel d 1. After ingesting the treated food, the cat absorbs the IgY through the gut and into the circulation, later secreting Fel d 1–specific IgY in the saliva during self grooming. The salivary IgY then purportedly neutralizes Fel d1 on the cat’s furry coat (Fig 1, A).3 When the treated food was eaten, dander Fel d 1 concentrations were reduced by an average of 47% after 3 weeks on the diet.3 The same researchers observed that cat salivary concentrations of Fel d 1 dropped over a relatively similar time course.4 Cat health was seemingly unaffected by the IgY; it is believed that Fel d 1 has a dispensable biologic role.5 A pilot crossover double-blinded chamber exposure challenge found that subjective throat and nose symptom scores improved significantly, and subgroup analysis found that nasal congestion was significantly improved.6

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