Cross-protection of AIT-induced antibodies to related allergens requires a high degree of structural identity.

Background: In contrast to sublingual immunotherapy (SLIT) with recombinant Mal d 1 (rMal d 1-SLIT), SLIT with rBet v 1 (rBet v 1-SLIT) induced Mal d 1-cross-reactive antibodies without IgE-blocking activity. To elucidate whether the development of cross-protective IgG responses depends on the degree of molecular identity of allergens we compared the cross-reactivity, cross-blocking activity, and affinity of SLIT-induced antibodies with allergens of varying amino acid sequence identities to Bet v 1 and Mal d 1, namely Cor a 1.04 (hazelnut), Pru av 1 (cherry), and Dau c 1 (carrot).

Adoptive Cell Therapy in Mice Sensitized to a Grass Pollen Allergen.

The proportion of patients with type I allergy in the world population has been increasing and with it the number of people suffering from allergic symptoms. Recently we showed that prophylactic cell therapy employing allergen-expressing bone marrow (BM) cells or splenic B cells induced allergen-specific tolerance in naïve mice. Here we investigated if cell therapy can modulate an established secondary allergen-specific immune response in pre-immunized mice.

Coupling of a Major Allergen to the Surface of Immune Cells for Use in Prophylactic Cell Therapy for the Prevention of IgE-Mediated Allergy.

Up to a third of the world's population suffers from allergies, yet the effectiveness of available preventative measures remains, at large, poor. Consequently, the development of successful prophylactic strategies for the induction of tolerance against allergens is crucial. In proof-of-concept studies, our laboratory has previously shown that the transfer of autologous hematopoietic stem cells (HSC) or autologous B cells expressing a major grass pollen allergen, Phl p 5, induces robust tolerance in mice.

Easy assessment of the avidity of polyclonal allergen-specific serum antibodies.

Introduction: Allergen-specific IgE-blocking IgG antibodies contribute to successful allergen immunotherapy (AIT), however, not much is known about their affinity. Since affinity measurements of polyclonal antibodies in serum are technically challenging we evaluated the applicability of acidic disruption of antibody-allergen complexes by a modified ELISA protocol with monoclonal antibodies (mAbs) specific for the relevant major allergens Betv1 and Mald1. Then, AIT-induced blocking and non-blocking Mald1-specific antibodies in sera from individuals with or without reduced apple allergy were compared.

Adoptive transfer of allergen-expressing B cells prevents IgE-mediated allergy.

Introduction: Prophylactic strategies to prevent the development of allergies by establishing tolerance remain an unmet medical need. We previously reported that the transfer of autologous hematopoietic stem cells (HSC) expressing the major timothy grass pollen allergen, Phl p 5, on their cell surface induced allergen-specific tolerance in mice. In this study, we investigated the ability of allergen-expressing immune cells (dendritic cells, CD4 T cells, CD8 T cells, and CD19 B cells) to induce allergen-specific tolerance in naive mice and identified CD19 B cells as promising candidates for allergen-specific cell therapy.

T-cell subset changes during the first year of pre-seasonal allergoid allergen-specific immunotherapy.

Allergen-specific immunotherapy (AIT) is the only treatment for type I allergy, which achieves long-lasting effects. Repeated subcutaneous applications of allergen extracts cause a protective antibody response and an immune deviation of T cells. In AIT with allergoids, chemically modified allergen extracts are injected.

Food-sensitized pediatric patients show colonic cow's milk protein-specific Th2 cells.

Food allergies have become a health concern worldwide. Around 6% to 10% of children are allergic to cow's milk proteins. We have previously characterized colorectal polyps in patients sensitized to food allergens.

The role of IgG and IgG as dominant IgE-blocking antibodies shifts during allergen immunotherapy.

Background: The induction of allergen-specific IgE-blocking antibodies is a hallmark of allergen immunotherapy (AIT). The inhibitory bioactivity has largely been attributed to IgG; however, our recent studies indicated the dominance of IgG early in AIT.

Objectives: Here, the IgE-blocking activity and avidity of allergen-specific IgG and IgG antibodies were monitored throughout 3 years of treatment.

Unilateral acute lung injury in pig: a promising animal model.

Background: Acute lung injury (ALI) occurs in 23% unilateral. Models of unilateral ALI were developed and used previously without clearly demonstrating the strictly unilateral nature and severity of lung injury by the key parameters characterizing ALI as defined by the American Thoracic Society (ATS). Thus, the use of unilateral ALI remained rare despite the innovative approach.

Bet v 1-independent sensitization to major allergens in Fagales pollen: Evidence at the T-cell level.

Background: In birch-dominated areas, allergies to pollen from trees of the order Fagales are considered to be initiated by the major birch pollen allergen Bet v 1. However, the sensitizing activity of Bet v 1-homologs in Fagales pollen might be underestimated. Allergen-specific T-cells are crucial in the sensitization process.

Identification of apple cultivars hypoallergenic for birch pollen-allergic individuals by a multidisciplinary in vitro and in vivo approach.

Background: Birch pollen-related apple allergy is the most frequent IgE-mediated food allergy in Central-Northern Europe with Mal d 1 as major allergen. Its concentration in apples varies with the cultivar and storage time. Year-round appealing, hypoallergenic cultivars still are needed to satisfy the nutritional needs of affected individuals.

How Do Pollen Allergens Sensitize?

Plant pollen is one of the main sources of allergens causing allergic diseases such as allergic rhinitis and asthma. Several allergens in plant pollen are panallergens which are also present in other allergen sources. As a result, sensitized individuals may also experience food allergies.

Development of a Sequence Searchable Database of Celiac Disease-Associated Peptides and Proteins for Risk Assessment of Novel Food Proteins.

Celiac disease (CeD) is an autoimmune enteropathy induced by prolamin and glutelin proteins in wheat, barley, rye, and triticale recognized by genetically restricted major histocompatibility (MHC) receptors. Patients with CeD must avoid consuming these proteins. Regulators in Europe and the United States expect an evaluation of CeD risks from proteins in genetically modified (GM) crops or novel foods for wheat-related proteins.

The secretome of irradiated peripheral blood mononuclear cells attenuates activation of mast cells and basophils.

Background: IgE-mediated hypersensitivity is becoming increasingly prevalent and activation of mast cells and basophils represent key events in the pathophysiology of allergy. We have previously reported that the secretome of γ-irradiated peripheral blood mononuclear cells (PBMCsec) exerts beneficial anti-inflammatory effects. Yet, its ability to alleviate allergic symptoms has not been investigated so far.

Neutrophils-typical atypical antigen presenting cells?

Neutrophils are the most abundant cells of the immune system and key in combating infections through phagocytosis, reactive oxygen species, neutrophil extracellular traps, and secretion of cytokines and antimicrobial peptides. Beyond this, they may influence the adaptive immune response by modulating CD4 T cell responses. In response to cytokines, mainly GM-CSF, but also IFN-γ and TNF-α, neutrophils express major histocompatibility complex class II molecules on their surface.

A dynamic single cell-based framework for digital twins to prioritize disease genes and drug targets.

Background: Medical digital twins are computational disease models for drug discovery and treatment. Unresolved problems include how to organize and prioritize between disease-associated changes in digital twins, on cellulome- and genome-wide scales. We present a dynamic framework that can be used to model such changes and thereby prioritize upstream regulators (URs) for biomarker- and drug discovery.

Isolation of nanobodies with potential to reduce patients' IgE binding to Bet v 1.

Background: Recent studies showed that a single injection of human monoclonal allergen-specific IgG antibodies significantly reduced allergic symptoms in birch pollen-allergic patients. Since the production of full monoclonal antibodies in sufficient amounts is laborious and expensive, we sought to investigate if smaller recombinant allergen-specific antibody fragments, that is, nanobodies, have similar protective potential. For this purpose, nanobodies specific for Bet v 1, the major birch pollen allergen, were generated to evaluate their efficacy to inhibit IgE-mediated responses.

Isotype-specific binding patterns of serum antibodies to multiple conformational epitopes of Bet v 1.

Background: Birch pollen is an important elicitor of respiratory allergy. The major allergen, Bet v 1, binds IgE exclusively via conformational epitopes.

Objective: We identified Bet v 1-specific epitope repertoires of IgE and IgG from birch pollen-allergic and nonallergic subjects.

Update of the S2k guideline on the management of IgE-mediated food allergies.

Not available.