Preventive allergen immunotherapy with inhalant allergens in children.

The efficacy and safety of preventive allergen immunotherapy (pAIT) in children are currently under investigation. Here, we provide an overview of pAIT with respiratory allergens concerning the prevention of new sensitizations, allergic disease onset and progression as well as further immunomodulatory effects. Three databases were searched for clinical pAIT studies in children. Selected publications were reviewed for preventive outcomes according to prevention level (primary, secondary, and tertiary), allergen type, administration route, dose, and treatment duration. The primary prevention approach appears safe but showed no allergen-specific effect on new sensitizations. Secondary prevention seems feasible and may induce regulatory T cell-mediated immunotolerance. The number of studies at these prevention levels is limited. Tertiary prevention with grass and/or tree pollen-based pAIT has shown efficacy in preventing disease progression from allergic rhinitis/conjunctivitis to asthma. Data on tertiary pAIT with house dust mites and other allergen types are inconclusive. Subcutaneous and sublingual routes appear similarly effective, but head-to-head comparative paediatric studies are scarce. Additionally, there are fewer placebo-controlled studies. Nevertheless, immunomodulatory outcomes of pAIT are encouraging. Currently, limited but favourably suggestive evidence is available for preventing respiratory allergic diseases in children by pAIT. Primary and secondary prevention have potential and warrant further investigation through well-designed studies.

Expression and regulation of Siglec-6 (CD327) on human mast cells and basophils.

BACKGROUND: Mast cells (MC) and basophils are effector cells of allergic reactions and display a number of activation-linked cell surface antigens. Of these antigens, however, only a few are functionally relevant and specifically expressed in these cells. OBJECTIVE: We sought to identify MC- and basophil-specific surface molecules and to study their cellular distribution and regulation during cytokine-induced and IgE-dependent activation. METHODS: Multicolor flow cytometry was performed to recognize surface antigens and to determine changes in antigen expression upon activation. RESULTS: We identified Siglec-6 (CD327) as a differentially regulated surface antigen on human MC and basophils. In the bone marrow, Siglec-6 was expressed abundantly on MC in patients with mastocytosis and in reactive states, but it was not detected on other myeloid cells, with the exception of basophils and monocytes. In healthy individuals, allergic patients, and patients with chronic myeloid leukemia (CML), Siglec-6 was identified on CD203c+ blood basophils, a subset of CD19+ B lymphocytes, and few CD14+ monocytes, but not on other blood leukocytes. CML basophils expressed higher levels of Siglec-6 than normal basophils. IL-3 promoted Siglec-6 expression on normal and CML basophils, and stem cell factor increased the expression of Siglec-6 on tissue MC. Unexpectedly, IgE-dependent activation resulted in downregulation of Siglec-6 in IL-3-primed basophils, whereas in MC, IgE-dependent activation augmented stem cell factor-induced upregulation of Siglec-6. CONCLUSIONS: Siglec-6 is a dynamically regulated marker of MC and basophils. Activated MC and basophils exhibit unique Siglec-6 responses, including cytokine-dependent upregulation and unique, cell-specific, responses to IgE-receptor cross-linking.

Limited role of children in transmission of SARS-CoV-2 virus in households-Immunological analysis of 26 familial clusters.

BACKGROUND: The impact of children on the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains uncertain. This study provides an insight into distinct patterns of SARS-CoV-2 household transmission in case of pediatric and adult index cases as well as age-dependent susceptibility to SARS-CoV-2 infection. METHODS: Immune analysis, medical interviewing, and contact tracing of 26 families with confirmed SARS-CoV-2 infection cases have been conducted. Blood samples were analyzed serologically with the use of a SARS-CoV-2-specific IgG assay and virus neutralization test (VNT). Uni- and multivariable linear regression and mixed effect logistic regression models were used to describe potential risk factors for higher contagiousness and susceptibility to SARS-CoV-2 infection. RESULTS: SARS-CoV-2 infection could be confirmed in 67 of 124 family members. Fourteen children and 11 adults could be defined as index cases in their households. Forty of 82 exposed family members were defined as secondarily infected. The mean secondary attack rate in households was 0.48 and was significantly higher in households with adult than with pediatric index cases (0.85 vs 0.19; p < 0.0001). The age (grouped into child and adult) of index case, severity of disease, and occurrence of lower respiratory symptoms in index cases were significantly associated with secondary transmission rates in households. Children seem to be equally susceptible to acquire a SARS-CoV-2 infection as adults, but they suffer milder courses of the disease or remain asymptomatic. CONCLUSION: SARS-CoV-2 transmission from infected children to other household members occurred rarely in the first wave of the pandemic, despite close physical contact and the lack of hygienic measures.

Multiple Drug Hypersensitivity in a Small Child with DRESS Syndrome - A Case Report.

Drug reaction with eosinophilia and systemic symptoms (DRESS) belongs to the group of severe cutaneous adverse reactions. Here we report a case of drug hypersensitivity against multiple antibiotics with DRESS in a young child with necrotizing pneumonia.

Acute exacerbations in children's interstitial lung disease.

INTRODUCTION: Acute exacerbations (AEs) increase morbidity and mortality of patients with chronic pulmonary diseases. Little is known about the characteristics and impact of AEs on children's interstitial lung disease (chILD). METHODS: The Kids Lung Register collected data on AEs, the clinical course and quality of life (patient-reported outcomes - PRO) of rare paediatric lung diseases. Characteristics of AEs were obtained. RESULTS: Data of 2822 AEs and 2887 register visits of 719 patients with chILD were recorded. AEs were characterised by increased levels of dyspnoea (74.1%), increased respiratory rate (58.6%) and increased oxygen demand (57.4%). Mostly, infections (94.4%) were suspected causing an AE. AEs between two register visits revealed a decline in predicted FEV1 (median -1.6%, IQR -8.0 to 3.9; p=0.001), predicted FVC (median -1.8%, IQR -7.5 to 3.9; p=0.004), chILD-specific questionnaire (median -1.3%, IQR -3.6 to 4.5; p=0.034) and the physical health summary score (median -3.1%, IQR -15.6 to 4.3; p=0.005) compared with no AEs in between visits. During the median observational period of 2.5 years (IQR 1.2-4.6), 81 patients died. For 49 of these patients (60.5%), mortality was associated with an AE. CONCLUSION: This is the first comprehensive study analysing the characteristics and impact on the clinical course of AEs in chILD. AEs have a significant and deleterious effect on the clinical course and health-related quality of life in chILD.

Early priming of asthma and respiratory allergies: Future aspects of prevention: A statement by the European Forum for Education and Research in Allergy and Airway Disease (EUFOREA) and the EAACI-Clemens von Pirquet Foundation.

In order to summarize recent research on the prevention of allergies-particularly asthma-and stimulate new activities for future initiatives, a virtual workshop sponsored by the EAACI Clemens von Pirquet foundation and EUFOREA was held in October 2021. The determinants of the "allergic march" as well as the key messages from intervention studies were reviewed by an international faculty of experts. Several unmet needs were identified, and a number of priorities for future studies were proposed.

Characterization of the antibody response to SARS-CoV-2 in a mildly affected pediatric population.

BACKGROUND: While children usually experience a mild course of COVID-19, and a severe disease is more common in adults, the features, specificities, and functionality of the SARS-CoV-2-specific antibody response in the pediatric population are of interest. METHODS: We performed a detailed analysis of IgG antibodies specific for SARS-CoV-2-derived antigens S and RBD by ELISA in 26 SARS-CoV-2 seropositive schoolchildren with mild or asymptomatic disease course, and in an equally sized, age- and gender-matched control group. Furthermore, a detailed mapping of IgG reactivity to a panel of microarrayed SARS-CoV-2 proteins and S-derived peptides was performed by microarray technology. The capacity of the antibody response to block RBD-ACE2 binding and virus neutralization were assessed. Results were compared with those obtained in an adult COVID-19 convalescent population. RESULTS: After mild COVID-19, anti-S and RBD-specific IgG antibodies were developed by 100% and 84.6% of pediatric subjects, respectively. No difference was observed in regards to symptoms and gender. Mounted antibodies recognized conformational epitopes of the spike protein and were capable to neutralize the virus up to a titer of ≥80 and to inhibit the ACE2-RBD interaction by up to 65%. SARS-CoV-2-specific IgG responses in children were comparable to mildly affected adult patients. CONCLUSION: SARS-CoV-2 asymptomatic and mildly affected pediatric patients develop a SARS-CoV-2-specific antibody response, which is comparable regarding antigen, epitope recognition, and the ability to inhibit the RBD-ACE2 interaction to that observed in adult patients after mild COVID-19.

Modeling the conversion between specific IgE test platforms for nut allergens in children and adolescents.

BACKGROUND: Multiplex tests allow for measurement of allergen-specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta-analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen-specific IgE to peanut/tree nut allergens from three IgE test platforms. METHODS: Plasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high-risk, pre-school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL-chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra-test correlations between PR-10 and nsLTP allergens were assessed. RESULTS: Using two regression methods, we demonstrated the ability to model allergen-specific relationships with acceptable measures of fit (r2  = 94%-56%) for peanut and tree nut sIgE testing at the extract and molecular-level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9. CONCLUSION: Our models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta-analysis.

Biologicals in atopic disease in pregnancy: An EAACI position paper.

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.

Peanut-induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry.

BACKGROUND: Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. METHODS: Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. RESULTS: 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). CONCLUSIONS: The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition.