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Background: Sublingual immunotherapy (SLIT) for grass pollen allergy can modify the natural history of allergic rhinitis and is associated with increased allergen‐specific IgG4. IgG4 competitively inhibits functional IgE on the surface of effector cells, such as mast cells and basophils, from binding to allergens. To further understand the important role memory B‐cell (Bmem) responses play in mediating the beneficial effects of SLIT, we assessed changes in allergen‐specific Bmem subsets induced by SLIT for grass pollen allergy. Methods: Blood samples were collected twice outside the pollen season from twenty‐seven patients with sensitization to ryegrass pollen (RGP; Lolium perenne) and seasonal rhinoconjunctivitis. Thirteen received 4‐month pre‐seasonal SLIT for grass pollen allergy, and 14 received standard pharmacotherapy only. Single‐cell RNA sequencing was performed on FACS‐purified Lol p 1‐specific Bmem before and after SLIT from four patients, and significant genes were validated by flow cytometry on the total cohort. Results: Four months of SLIT increased RGP‐specific IgE and IgG4 in serum and induced two Lol p 1‐specific Bmem subsets with unique transcriptional profiles. Both subsets had upregulated expression of beta 1 integrin ITGB1 (CD29), whereas IGHE (IgE), IGHG4 (IgG4), FCER2 (CD23), and IL13RA1 were upregulated in one subset. There was an increase in the proportion of Lol p 1+ Bmem expressing surface IgG4, CD23, and CD29 after SLIT. Conclusions: A clinically successful 4 months course of SLIT for grass pollen allergy induces two transcriptionally unique Bmem fates. Associated changes in surface‐expressed proteins on these Bmem subsets can be used as early biomarkers for treatment effects. [ABSTRACT FROM AUTHOR]

RBD-specific Bmem were detected in all donors after first and second doses, with significantly higher numbers (1.7-fold) post-dose 2 (Figure 1F, Figure S1A-D). The second COVID-19 mRNA vaccine dose enhances the capacity of Spike-specific memory B cells to bind Omicron BA.2 (A) Participants were sampled pre-BNT162b2 vaccination, 3 weeks post-dose 1, and 4 weeks post-dose 2 with a median of 23 days (range: 21-39 days) between doses. [Extracted from the article]

Background: IgG2 responses are associated with repeated antigen exposure and display highly mutated variable domains. A recent study highlighted a role of IgG2+ memory B cells and allergen‐specific IgG2 levels after a 3rd consecutive pre‐seasonal sublingual allergen immunotherapy (AIT) with grass pollen tablet. Herein, we aim to explore changes in allergen‐specific IgG2 in individuals undergoing house dust mite immunotherapy (HDM‐AIT) and explore whether the interrelationship with other humoral responses (i.e., IgG4 and IgE) may discriminate between high and low responders. Methods: Levels of serum Dermatophagoides pteronyssinus and Dermatophagoides farinae‐specific IgG2, IgG4, and IgE antibodies were measured by ELISA or ImmunoCap in a sub‐group of individuals enrolled in a randomized, double‐blind, placebo‐controlled, sublingual AIT study evaluating the safety and efficacy of a 300 IR HDM tablet. Results: After 1‐year sublingual AIT, HDM‐specific serum IgG2 responses increase mostly in high versus low responders and are distinctive according to the clinical benefit. Higher correlation between HDM‐specific IgG2, IgE, and/or IgG4 responses is seen in subjects benefiting the most from HDM‐AIT as indicated by changes in Average Total Combined Scores. More strikingly, statistically significant correlation between HDM‐specific IgG2 and IgE responses is only observed in individuals stratified as high responders. Conclusions: We provide evidence for coordinated serum immune responses upon AIT in HDM‐allergic subjects exhibiting high clinical benefit when compared with low responders. Assessing HDM‐specific IgE, IgG2, and IgG4 in serum could be used as follow‐up combined markers to support decision as to AIT continuation and/or adaptation. [ABSTRACT FROM AUTHOR]

Background: While treatment for atopic rhinitis is aimed mostly to relieve symptoms, only allergen‐specific immunotherapy (AIT) is targeted to modify the natural history of allergic diseases. This results in sustained clinical tolerance, even when treatment has stopped. The immunomodulatory effects of AIT are attributed mainly to increased regulatory T‐cell function and increased allergen‐specific IgG4, yet little is known about the effect on the memory B‐cell compartment. Objective: We aimed to examine the effects of AIT on the IgE‐ and IgG subclass‐expressing memory B cells. Methods: We recruited 29 patients with atopic seasonal rhinoconjunctivitis and performed a longitudinal analysis of the peripheral immune compartment before, during, and after sublingual immunotherapy (SLIT) for allergy to temperate grass pollen, predominantly to ryegrass pollen (RGP; Lolium perenne). Using flow cytometry on peripheral blood mononuclear cells and serum immunoassays, we analyzed the effects of a 4 months preseasonal treatment regimen comprising two or three courses in consecutive years on circulating IgE+ and IgG+ memory B cells and allergen‐specific Ig levels. Results: SLIT increased RGP‐specific serum IgG2 and IgG4, as well as the frequencies of IgG2+ and IgG4+ memory B cells, whereas no effect was observed on the IgE+ memory B‐cell compartment. Furthermore, SLIT enhanced proportions of regulatory T cells specific to RGP. These changes were associated with clinical improvement. Conclusion: Our data provide evidence for immunological effects of SLIT on B‐cell memory. Skewing responses toward IgG2 and IgG4 subclasses might be a mechanism to suppress IgE‐mediated allergic responses. [ABSTRACT FROM AUTHOR]

This article discusses a study on the effects of allergen immunotherapy (AIT) on type 2 memory B cells (Bmem) in patients with bee venom and ryegrass pollen allergies. The study found that successful AIT led to an increase in allergen-specific type 2 Bmem expressing certain proteins. The study also observed changes in the phenotype of type 2 Bmem after AIT. The authors suggest that these changes may contribute to the effectiveness of AIT, but more research is needed to understand the long-term effects. The document also provides acknowledgments, funding information, author affiliations, references, and contact information for the corresponding author. The data from the study are available upon request. [Extracted from the article]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited., Methods: This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint., Results: We observed a significant decrease in NPS from a median value of 6 (IQR 5-6) at baseline to 1.0 (IQR 0.0-2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49-70) at baseline to 11 (IQR 6-21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria., Conclusions: Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic., Methods: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity., Results: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred., Conclusions: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease associated with a substantial personal and socioeconomic burden. Monitoring of patient-reported outcomes by mobile technology offers the possibility to better understand real-life burden of CRS., Methods: This study reports on the cross-sectional evaluation of data of 626 users of mySinusitisCoach (mSC), a mobile application for CRS patients. Patient characteristics of mSC users were analysed as well as the level of disease control based on VAS global rhinosinusitis symptom score and adapted EPOS criteria., Results: The mSC cohort represents a heterogeneous group of CRS patients with a diverse pattern of major symptoms. Approximately half of patients reported nasal polyps. 47.3% of all CRS patients were uncontrolled based on evaluation of VAS global rhinosinusitis symptom score compared to 40.9% based on adapted EPOS criteria. The impact of CRS on sleep quality and daily life activities was significantly higher in uncontrolled versus well-controlled patients. Half of patients had a history of FESS (functional endoscopic sinus surgery) and reported lower symptom severity compared to patients without a history of FESS, except for patients with a history of more than 3 procedures. Patients with a history of FESS reported higher VAS levels for impaired smell., Conclusion: Real-life data confirm the high disease burden in uncontrolled CRS patients, clearly impacting quality of life. Sinus surgery improves patient-reported outcomes, but not in patients with a history of more than 3 procedures. Mobile technology opens a new era of real-life monitoring, supporting the evolution of care towards precision medicine., (© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: While treatment for atopic rhinitis is aimed mostly to relieve symptoms, only allergen-specific immunotherapy (AIT) is targeted to modify the natural history of allergic diseases. This results in sustained clinical tolerance, even when treatment has stopped. The immunomodulatory effects of AIT are attributed mainly to increased regulatory T-cell function and increased allergen-specific IgG 4 , yet little is known about the effect on the memory B-cell compartment., Objective: We aimed to examine the effects of AIT on the IgE- and IgG subclass-expressing memory B cells., Methods: We recruited 29 patients with atopic seasonal rhinoconjunctivitis and performed a longitudinal analysis of the peripheral immune compartment before, during, and after sublingual immunotherapy (SLIT) for allergy to temperate grass pollen, predominantly to ryegrass pollen (RGP; Lolium perenne). Using flow cytometry on peripheral blood mononuclear cells and serum immunoassays, we analyzed the effects of a 4 months preseasonal treatment regimen comprising two or three courses in consecutive years on circulating IgE + and IgG + memory B cells and allergen-specific Ig levels., Results: SLIT increased RGP-specific serum IgG 2 and IgG 4 , as well as the frequencies of IgG 2 + and IgG 4 + memory B cells, whereas no effect was observed on the IgE + memory B-cell compartment. Furthermore, SLIT enhanced proportions of regulatory T cells specific to RGP. These changes were associated with clinical improvement., Conclusion: Our data provide evidence for immunological effects of SLIT on B-cell memory. Skewing responses toward IgG 2 and IgG 4 subclasses might be a mechanism to suppress IgE-mediated allergic responses., (© 2019 The Authors. Allergy published by John Wiley & Sons Ltd.)

Allergic diseases are the most common chronic immune-mediated disorders and can manifest with an enormous diversity in clinical severity and symptoms. Underlying mechanisms for the adverse immune response to allergens and its downregulation by treatment are still being revealed. As a result, there have been, and still are, major challenges in diagnosis, prediction of disease progression/evolution and treatment. Currently, the only corrective treatment available is allergen immunotherapy (AIT). AIT modifies the immune response through long-term repeated exposure to defined doses of allergen. However, as the treatment usually needs to be continued for several years to be effective, and can be accompanied by adverse reactions, many patients face difficulties completing their schedule. Long-term therapy also potentially incurs high costs. Therefore, there is a great need for objective markers to predict or to monitor individual patient's beneficial changes in immune response during therapy so that efficacy can be identified as early as possible. In this review, we specifically address recent technical developments that have generated new insights into allergic disease pathogenesis, and how these could potentially be translated into routine laboratory assays for disease monitoring during AIT that are relatively inexpensive, robust and scalable., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision-makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real-world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients' organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Asthma and other Th2 inflammatory conditions have been associated with increased susceptibility to viral infections. The mechanisms by which Th2 cytokines can influence immune responses to infections are largely unknown., Methods: We measured the effects of Th2 cytokines (IL-4 and IL-13) on bronchial epithelial cell innate immune antiviral responses by assessing interferon (IFN-β and IFN-λ1) induction following rhinovirus (RV)-16 infection. We also investigated the modulatory effects of Th2 cytokines on Toll-like receptor 3 (TLR3), interferon-responsive factor 3 (IRF3) and nuclear factor (NF)-kB, that is key molecules and transcription factors involved in the rhinovirus-induced interferon production and inflammatory cascade. Pharmacological and redox modulation of these pathways was also assessed., Results: Th2 cytokines impaired RV-16-induced interferon production, increased rhinovirus replication and impaired TLR3 expression in bronchial epithelial cells. These results were replicated in vivo: we found increased IL-4 mRNA levels in nasal epithelial cells from nasal brushing of atopic rhinitis patients and a parallel reduction in TLR3 expression and increased RV-16 replication compared to nonatopic subjects. Mechanistically, Th2 cytokines impaired RV-16-induced activation of IRF3, but had no effects on RV-16-induced NF-kB activation in bronchial epithelial cell cultures. N-acetylcysteine and phosphoinositide 3-kinase (PI3K) inhibitor restored the inhibitory effects of Th2 cytokines over RV-16-induced activation of IRF3., Conclusions: IL-4 and IL-13, through inhibition of TLR3 expression and signalling (IRF3), impair immune response to RV-16 infection. These data suggest that Th2 conditions increase susceptibility to infections and identify pharmacological approaches with potential to restore impaired immune response in these conditions., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Numerous factors affect the evolution of respiratory allergy, in children, but little is known in adults. We assessed in a prospective study the influence of the type of allergen on the progression of disease., Methods: Outpatients, with respiratory allergy underwent skin tests and pulmonary function/methacholine challenge at baseline and after 3 years. Patients were subdivided in pure rhinitis or rhinitis + bronchial hyperreactivity (BHR). In polysensitized subjects a single relevant allergen (mites, grasses, birch, Parietaria) was identified based on symptom distribution and when needed on nasal challenge., Results: 6750 patients (age range 12-46) were studied. Of them, 17.8% were monosensitized but this percentage decreased to 10.4% after 3 years (P < 0.05). Subjects with pure rhinitis were 81% at the beginning and 48% at the end. After 3 years, the patients with bronchial responsiveness increased from 18% to 58% for mites, 22% to 49% for birch, 18% to 44% for grasses, 17% to 32% for Parietaria, with a significant difference among allergens (P < 0.05). Almost the same was seen in monosensitized subjects, being mites most likely to cause a worsening. All patients with BHR at baseline received immunotherapy. In these patients the onset of new sensitizations was significantly lower than in the group (pure rhinitis) receiving drugs only and lower airways symptoms disappeared more frequently., Conclusion: The different type of allergen influences the course of the disease, as well as the use of immunotherapy.

Background: Some aspects of sublingual immunotherapy (SLIT) still need to be addressed: magnitude of the clinical efficacy, effect on the bronchial hyperreactivity adherence to treatment, preventive effect. We attempted to clarify these points in a randomized open, controlled, two parallel group study in a real-life setting., Methods: Five hundred and eleven patients with allergic rhinitis with or without intermittent asthma were randomized to drugs only or drugs + SLIT (rate 2 : 3) for 3 years. The clinical score (symptoms + drug intake) was measured each year during the allergen exposure. Pulmonary function test, methacholine challenge and skin tests were performed at the beginning and at the end of the study. Adherence to treatment was assessed by measuring the consumed extract., Results: Three hundred and nineteen patients received SLIT and 192 drugs only. Dropouts were 15% in the SLIT group and 12% in the controls. There was a significant improvement of clinical scores in the SLIT group: baseline 147 +/- 3.3, first year 72.9 +/- 1.3, second year 68.3 +/- 1.8, third year 54.7 +/- 2.8 (P < 0.0001 vs baseline)., Control Group: baseline 138 +/- 2.3, first year 124.1 +/- 3.7, second year 111 +/- 3.3, third year 121 +/- 3.8 (P = NS). Only four patients reported systemic itching. Adherence was >80% in 72% and >60% in 18% of patients. The number of patients with a positive MCh challenge decreased significantly after 3 years only in the SLIT group. New skin sensitizations appeared in 38% of the controls and in 5.9% of the SLIT patients (P = 0.01)., Conclusion: Sublingual immunotherapy approximately halved the clinical scores and significantly reduced the bronchial hyperreactivity. Similarly to subcutaneous immunotherapy, SLIT displayed a preventive effect on the onset of new skin sensitizations. The adherence rate was quantitatively satisfactory., (Copyright 2004 Blackwell Munksgaard)