CD‐sens: a biological measure of immunological changes stimulated by ASIT

Background: Allergen‐specific immunotherapy (ASIT) in allergic rhinitis and asthma is the only treatment that effects the long‐term development of these diseases. Basophil allergen threshold sensitivity, CD‐sens, which is a valuable complement to resource‐demanding clinical challenge tests, was used to monitor the initiation of ASIT induced allergen ‘blocking activity’. Methods: Patients IgE‐sensitized to timothy (n = 14) or birch (n = 19) pollen were started on conventional (8–16 weeks) or ultra rush ASIT, respectively, and followed by measurements of CD‐sens, allergen binding activity (ABA) and serum IgG4‐ and IgE‐antibody concentrations. Results: CD‐sens decreased during the early phase of ASIT‐treatment. In parallel, ABA increased and correlated significantly with the increasing levels of IgG4 antibody concentrations. High dosages of allergen were more effective while mode of dosing up did not seem to matter. No change was seen in basophil reactivity. Conclusion: CD‐sens and ABA, in contrast to basophil reactivity, seem to be promising tools to monitor protective immune responses initiated by ASIT.     

Basophil Histamine Release and Humoral Changes during Immunotherapy

An in vitro pilot study was performed to determine whether basophil cell-bound specific IgE was correlated to serum-specific IgE and to basophil cell sensitivity during immunotherapy with a well-documented treatment. The findings showed a clear dissociation between these three parameters, which is in contrast to the situation before hyposensitization and to our previous study in a comparable group of non-hyposensitized patients, where highly significant correlations were observed. Further investigations are in progress to clarify whether the dissociation is involved in the clinical improvement.     

Basophil Histamine Release in Cord Blood Regulatory Role of IgE

Thirty-two cord blood samples were studied for histamine releasing capability by using a sensitive glass microfibre-based histamine analysis. Histamine was obtained after challenge with anti-IgE in 24 of the 32 samples. However, the net release in cord blood was only 25% of that in adult blood and no relationship was found between histamine release response, total IgE in cord plasma, and a family history of atopic diseases. The low histamine release in cord blood seemed to be associated with the immunological IgE receptor complex activation and not with an immature basic cell function, since the calcium ionophore A23187 which bypasses the receptor complex induced identical histamine release curves in cord and adult blood. Furthermore, when comparing the results of passive sensitization of basophils from new-born and adult persons, the new-born basophils possessed a significant fraction of free IgE receptors, whereas in adults most of the receptors were occupied by IgE.     

An immunoglobulin E-reactive chimeric human immunoglobulin G1 anti-idiotype inhibits basophil degranulation through cross-linking of FcɛRI with FcγRIIb

Background IgE binds to mast cells and basophils via its high‐affinity receptor, Fc?RI, and cross‐linking of Fc?RI‐bound IgE molecules by allergen leads to the release of allergic mediators characteristic of type I hypersensitivity reactions. Previous work has shown that cross‐linking of Fc?RI with FcγRIIb, an ITIM‐containing IgG receptor, leads to inhibition of basophil triggering. 2G10, a chimeric human IgG1 anti‐idiotype, has broad reactivity with human IgE and as such has the potential to bind simultaneously to Fc?RI‐bound IgE, via its Fab regions, and the negative regulatory receptor, FcγRIIb, via its Fc region. Objective To assess the ability of human 2G10 to inhibit anti‐IgE and allergen‐driven basophil degranulation through cross‐linking of Fc?RI‐bound IgE with FcγRIIb. Methods 2G10 was assessed for its ability to bind to FcγRIIb on transfected cells and on purified basophils. In the basophil degranulation assay, basophils were purified from peripheral blood of atopic individuals and activated with either anti‐IgE or the house dust mite allergen Der p 1, in the presence or absence of human 2G10. Basophil activation was quantified by analysis of CD63 and CD203c expression on the cell surface, and IL‐4 expression intracellularly, using flow cytometery. Results Human 2G10 was able to bind to FcγRIIb on transfected cells and on purified basophils, and induce a dose‐dependent inhibition of both anti‐IgE and Der p 1‐driven degranulation of basophils. Conclusion The inhibition of basophil degranulation by the human IgG1 anti‐idiotype 2G10 highlights the therapeutic potential of IgE‐reactive IgG antibodies in restoring basophil integrity through recruitment of the inhibitory receptor FcγRIIb.     

Food allergy severity predictions based on cellular in vitro tests

ABSTRACT

Introduction

Food allergy is increasing in prevalence and the severity of allergic reactions is unpredictable. Identifying food-allergic patients at high risk of severe reactions would allow us to offer a personalized and improved management for these patients.