IgE-Mediated Allergen Presentation and Blocking Antibodies: Regulation of T-Cell Activation in Allergy

Neerven, R. J. Joost van; Knol, Edward F.; Ejrnaes, Anne M; Würtzen, Peter Adler

doi:10.1159/000094714

Cited by 116 publications

(97 citation statements)

References 205 publications

(112 reference statements)

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“…It has however been hypothesized that this pathway plays a role in perpetuating allergies, when serum concentrations of allergen-specific IgE are high (66), and there is accumulating experimental evidence that the IgE/CD23-mediated allergen presentation indeed plays a role in atopic disease. Sera from allergic patients were shown to contain sufficient amounts of allergen-specific IgE to induce presentation of the allergen by CD23 ϩ EBV-transformed B cells in vitro (27,67) and IgE/CD23-mediated allergen presentation is decreased in patients undergoing successful specific immunotherapy or anti-IgE treatment (67). Perhaps not only allergens, but also certain pathogens, induce high levels of specific IgE, which may then aid in the induction of an efficient protective immune response.…”

Section: Discussionmentioning

confidence: 99%

A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen

Hjelm

Karlsson

Heyman

2008

The Journal of Immunology

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Ag administered i.v. to mice along with specific IgE or IgG2a induces higher Ab- and CD4+ T cell responses than Ag administered alone. The IgE effect is completely dependent on the low-affinity receptor for IgE, CD23, whereas the IgG2a effect depends on activating FcγRs. In vitro studies suggest that IgE/Ag is presented more efficiently than Ag alone to CD4+ T cells by CD23+ B cells and that IgG2a/Ag is presented by FcγR+ dendritic cells (DCs). In this study, we investigate in vivo the early events leading to IgE- and IgG2a-mediated enhancement of immune responses. OVA administered i.v. in PBS in combination with specific IgE binds circulating B cells after 5 min and is found in B cell follicles bound to follicular B cells (CD23high) after 30 min. This novel B cell-dependent route of entry is specific for IgE because IgG2a-Ag complexes were trapped in the marginal zone. OVA-specific CD4+ T cells were found at the T-B border in the T cell zones 12 h after immunization both with IgE/OVA or IgG2a/OVA and proliferated vigorously after 3 days. The findings suggest that IgE- and IgG2a-immune complexes are efficient stimulators of early CD4+ T cell responses and that Ag bound to IgE has a specific route for transportation into follicles.

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Section: Discussionmentioning

confidence: 99%

A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen

Hjelm

Karlsson

Heyman

2008

The Journal of Immunology

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“…In fourth place, within weeks to months, a dose-dependent increase in allergen-specific IgG4 is observed (58). These allergen-specific IgG4 antibodies are supposed to act as blocking antibodies interacting at the level of IgE-mediated effector cell activation (49,(59)(60)(61)(62). In particular, IL-10 produced by allergen-specific T regulatory cells and B regulatory cells has been linked to IgG4 (63).…”

Section: Time (Y)mentioning

confidence: 99%

Markers of tolerance development to food allergens

Ponce

Diesner

Szépfalusi

et al. 2016

Allergy

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IgE-mediated reactions to food allergens are the most common cause of anaphylaxis in childhood. Although allergies to cow's milk, egg, or soy proteins, in contrast to peanut and tree nut allergens, resolve within the first 6 years of life in up to 60% due to natural tolerance development, this process is not well understood. At present, there is no cure or treatment for food allergy that would result in an induction of tolerance to the symptom-eliciting food. Avoidance, providing an emergency plan and education, is the standard of treatment. Oral immunotherapeutic approaches have been proven reasonable efficacy; however, they are associated with high rates of side-effects and low numbers of patients achieving tolerance. Nevertheless, mechanisms that take place during oral immunotherapy may help to understand tolerance development. On the basis of these therapeutic interventions, events like loss of basophil activation and induction of regulatory lymphocyte subsets and of blocking antibodies have been described. Their functional importance at a clinical level, however, remains to be investigated in detail. Consequently, there is eminent need to understand the process of tolerance development to food allergens and define biomarkers to develop and monitor new treatment strategies for food allergy.IgE-mediated food allergy represents the most important cause of anaphylaxis in childhood. While milk and egg allergy are associated with a high rate of natural tolerance development within the first 6 years of life, this is less clear for other food allergies. Consequently, once it is communicated the diagnosis persists often lifelong severely impacting the quality of life of the patient and the environment despite the recommendation to reconsider clinical tolerance development from time to time.Currently, avoidance, providing an emergency plan and teaching, is the standard of treatment; however, there is no cure or treatment that has reached the level of recommendation to re-induce tolerance to the symptom-eliciting food. Tolerance assessment occurs either via oral food challenges or due to unintended exposure. Given the cost and time intensiveness of oral food challenges and its potential harmfulness, there is eminent need to understand the process of tolerance development and define markers thereof to develop and monitor new treatment strategies for food allergy. This review aimed to provide an overview on recent advances regarding markers and mechanisms of tolerance development to food allergens.Oral tolerance in the context of food allergy is considered to occur if the antigen/food can be ingested without problems despite prolonged periods of avoidance, while the status of desensitization is strictly dependent on regular ingestion of the respective food in order to confer protection from allergic reactions. Currently, there is no general consensus on the exact time frame of avoidance and re-exposure that would allow the usage of the terminus tolerance that is considered equivalent to cure in the context of or...

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“…IgG4 is a unique antibody with a Fab-arm exchange ability to generate monovalent and non-cross-linking antibodies [6]. Although there is no clear correlation between serum concentrations of specific IgG4 and clinical efficacy [4], SIT-induced specific IgG4 has been shown to act as a blocking antibody by competing with specific IgE in the binding of allergens affecting mast cells and basophil activity, and interfering with IgE-facilitated antigen presentation, thereby preventing the allergen-dependent activation of T cells [7,8]. The blocking ability of specific IgG4 is still in effect after completing the course of SIT although the levels of IgG4 have decreased [9].…”

Section: Introductionmentioning

confidence: 99%

Specific IgG4 Production during House Dust Mite Immunotherapy among Age, Gender and Allergic Disease Populations

Lai

Xiao

et al. 2012

Int Arch Allergy Immunol

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Background: Specific IgG4 induced by allergen-specific immunotherapy (SIT) is an immunological marker related to the appearance of clinical tolerance. But specific IgG4 levels in different age, gender and allergic disease populations have not been fully investigated. Methods: This study involved 226 children and 109 adults with allergic rhinitis and/or asthma receiving a 156-week course of Dermatophagoides pteronyssinus (Der p) subcutaneous SIT. Symptom and medication scores, forced expiratory volume after 1 s (FEV₁) and Der p-specific IgG4 levels at weeks 0, 5, 10, 25, 52, 104 and 156 were analyzed. Results: Rhinitis symptom and medication scores and FEV₁ % predicted in children showed significantly greater improvement than in adults at week 104 and 156 (p < 0.05). Levels of Der p-specific IgG4 showed a significant increase after 10 weeks of subcutaneous SIT (p < 0.0001) and continued to increase during the 156-week SIT period. Before SIT, the initial Der p-specific IgG4 level was higher in children than adults (p = 0.0004). The increase ratio of Der p-specific IgG4 was higher in children than adults at 52 weeks (p < 0.001) and 104 weeks (p = 0.0156) of SIT, and was higher in rhinitis compared to asthma patients at 156 weeks of SIT (p = 0.0244). There was no difference between males and females at any time points. Conclusion: Children are more responsive to SIT, demonstrating clinical and FEV₁ improvement and producing higher levels of allergen-specific IgG4 during a shorter SIT period compared to adults. Rhinitis patients show a higher increase in specific IgG4 compared to patients with asthma symptoms. The increase of Der p-specific IgG4 reflects a specific response of the immune system towards the SIT vaccine being administrated.

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IgE-Mediated Allergen Presentation and Blocking Antibodies: Regulation of T-Cell Activation in Allergy

Cited by 116 publications

References 205 publications

A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen

A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen

Markers of tolerance development to food allergens

Specific IgG4 Production during House Dust Mite Immunotherapy among Age, Gender and Allergic Disease Populations

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