Allergen Immunotherapy for the Prevention and Treatment of Asthma.

Allergic asthma is the predominant phenotype among asthmatics. Although conventional pharmacotherapy is a central component in the management of asthma, it does not enable control of asthma symptoms in all patients. In recent decades, some uncontrolled asthmatic patients, especially those with allergic asthma, have benefited from biological therapies.

Accurate determination of house dust mite sensitization in asthma and allergic rhinitis through cytometric detection of Der p 1 and Der p 2 binding on basophils (CytoBas).

Background: House dust mite (HDM) is the most common allergen trigger globally for allergic rhinitis and atopic asthma.

Objectives: To expedite accurate confirmation of allergen sensitization, we designed fluorescent allergen tetramers to directly stain specific IgE on basophils to detect specific allergen sensitization using the flow cytometric CytoBas assay.

Methods: Recombinant proteins of major HDM allergens (component), Der f 1, Der p 1, and Der p 2 were biotinylated and conjugated with fluorochrome streptavidins as tetramers.

Deciphering Differential Behavior of Immune Responses as the Foundation for Precision Dosing in Allergen Immunotherapy.

Like in many fields of medicine, the concept of precision dosing has re-emerged in routine practice in allergology. Only one retrospective study on French physicians' practice has addressed this topic so far and generated preliminary data supporting dose adaptation, mainly based on experience, patient profile understanding and response to treatment. Both intrinsic and extrinsic factors shape the individual immune system response to allergen immunotherapy (AIT).

Current advances in house dust mite allergen immunotherapy (AIT): Routes of administration, biomarkers and molecular allergen profiling.

Allergy to house dust mites (HDM) is a perennial respiratory disease that affect more than half a billion people worldwide. Dermatophagoides pteronyssinus and D. farinae, two HDM species, are major sources of indoor allergens triggering allergic inflammation.

Molecular reactivity profiling upon immunotherapy with a 300 IR sublingual house dust mite tablet reveals marked humoral changes towards major allergens.

Background: Molecular antibody reactivity profiles have not yet been studied in depth in patients treated by sublingual house dust mite (HDM) tablet immunotherapy. Humoral immune responses to a large panel of HDM mite allergens were studied using allergen microarray technology in a subset of clinically defined high and low responder patients from a double-blind placebo-controlled allergen-specific immunotherapy (AIT) trial using sublingual 300 IR HDM tablets.

Methods: Serum levels of IgE, IgG and IgG to 13 Dermatophagoides pteronyssinus molecules were measured at baseline and after 1-year AIT, using allergen microarrays in 100 subjects exhibiting high or low clinical benefit.

Coordinated IgG2 and IgE responses as a marker of allergen immunotherapy efficacy.

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.

Decrease in CD38 TH2A cell frequencies following immunotherapy with house dust mite tablet correlates with humoral responses.

Background: In line with evidence for a role of pathogenic TH2A in seasonal allergies, we previously showed that individuals suffering from food allergy exhibited a decrease in circulating TH2A cells following multi-food immunotherapy. Herein, we aim to confirm the decline of TH2A cells in individuals undergoing house dust mite immunotherapy (HDM-AIT) and extend our observation to a new subset of CD38 expressing activated TH2A cells.

Methods: The frequencies of TH2A and CD38 TH2A cells were analysed by flow cytometry in blood cells from 182 Japanese HDM-allergic individuals included in a 1-year clinical trial assessing the efficacy of HDM tablets.

Bet v 1 contiguous overlapping peptides anchored to virosomes with TLR4 agonist enhance immunotherapy efficacy in mice.

Background: Whereas sublingual allergen immunotherapy (AIT) is routinely performed without any adjuvant or delivery system, there is a strong scientific rationale to better target the allergen(s) to oral dendritic cells known to support regulatory immune responses by using appropriate presentation platforms.

Objective: To identify a safe presentation platform able to enhance allergen-specific tolerance induction.

Methods: Virosomes with membrane-integrated contiguous overlapping peptides (COPs) of Bet v 1 and TLR4 or TLR2/TLR7 agonists were assessed for induction of Bet v 1-specific IgG1, IgG2a and IgE antibodies, hypersensitivity reactions and body temperature drop following subcutaneous injection in naive CD-1 mice.

Clinical efficacy of sublingual immunotherapy tablets for allergic rhinitis is unlikely to be derived from allergen-release data.

: Allergen bioavailability underpins the efficacy and safety of SLIT tablets. Three product-related factors are likely to influence this: tablet potency, formulation and sublingual holding time. : Tablet formulation determines the rate and extent of solubilized allergen release.

CCR10 ILC2s with ILC1-like properties exhibit a protective function in severe allergic asthma.

Background: We previously showed that patients with severe allergic asthma have high numbers of circulating ILC2s expressing CCR10.

Method: Herein, CCR10 ILC2s were further analyzed in the blood of healthy individuals or patients with allergic and non-allergic asthma. Characteristics of human CCR10 and CCR10 ILC2s were assessed by flow cytometry as well as single-cell multiplex RT-qPCR.

Characterization of epitope specificities of reference antibodies used for the quantification of the birch pollen allergen Bet v 1.

Background: Accurate allergen quantification is needed to document the consistency of allergen extracts used for immunotherapy. Herein, we characterize the epitope specificities of two monoclonal antibodies used in an ELISA for the quantification of the major birch pollen allergen Bet v 1, established as a reference by the BSP090 European project.

Methods: The ability of mAbs 5B4 and 6H4 to recognize Bet v 1 isoforms was addressed by immunochromatography.

A combined transcriptome and proteome analysis extends the allergome of house dust mite Dermatophagoides species.

Background: House dust mites (HDMs) such as Dermatophagoides farinae and D. pteronyssinus represent major causes of perennial allergy. HDM proteomes are currently poorly characterized, with information mostly restricted to allergens.

Comparative analysis of the oral mucosae from rodents and non-rodents: Application to the nonclinical evaluation of sublingual immunotherapy products.

Background: A comparative characterization of the oral mucosa in various animals is needed to identify the best animal model(s) for nonclinical evaluation of sublingual immunotherapy products. With this aim, we studied the histological characteristics and immune cell infiltrates of oral mucosae from common animal species.

Methods: Three oral regions (i.

Differences and similarities between sublingual immunotherapy of allergy and oral tolerance.

Allergen immunotherapy is the only treatment altering the natural course of IgE-mediated allergies. Whereas the subcutaneous route for immunotherapy (SCIT) has been historically considered as a reference, we discuss herein the relative advantages of the sublingual and oral routes as alternatives to SCIT in order to elicit allergen-specific tolerance. The buccal and gut immune systems are similarly organized to favor immune tolerance to antigens/allergens, due to the presence of tolerogenic dendritic cells and macrophages promoting the differentiation of CD4 regulatory T cells.

Effector and regulatory dendritic cells display distinct patterns of miRNA expression.

Introduction: MicroRNAs (miRNAs) contribute to the regulation of dendritic cell (DC) polarization, thereby influencing the balance of adaptive immune responses. Herein, we studied the expression of miRNAs in polarized DCs and analyzed whether expression of these miRNAs could be associated with allergic rhinitis and allergen immunotherapy (AIT) outcome.

Method: Using specific culture conditions, we differentiated immature human monocyte-derived DCs into DC1, DC2, and DCreg subsets (supporting the differentiation of T 1, T 2 or regulatory T cells, respectively).

Enhancing Allergen-Presentation Platforms for Sublingual Immunotherapy.

Sublingual immunotherapy (SLIT) relies on high doses of allergens to treat patients with type I allergies. Although SLIT is commonly performed without any adjuvant or delivery system, allergen(s) could be further formulated with allergen-presentation platforms to better target oral dendritic cells eliciting regulatory immune responses. Improving the availability of allergens to the immune system should enhance SLIT efficacy, while allowing to decrease allergen dosing.