Effect of Anti-IgE Therapy in Patients with Peanut Allergy

Leung, Donald Y.M.; Sampson, Hugh A.; Yunginger, John W.; Burks, A. Wesley; Schneider, Lynda C.; Wortel, Cornelis H.; Davis, Frances M.; Hyun, John D.; Shanahan, William R.

doi:10.1056/nejmoa022613

Cited by 616 publications

(325 citation statements)

References 30 publications

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“…However, the high serum IgE levels seen in AD may limit the usefulness of this antibody, although it may have a role in food-induced AD. In this respect, treatment of a population of peanut-allergic patients with anti-IgE significantly increased their threshold of sensitivity to peanuts on oral food challenge, suggesting protection against unintended ingestion of the food allergen (31).…”

Section: New Approaches To Modulate Atopic Inflammationmentioning

confidence: 95%

New insights into atopic dermatitis

Leung¹,

Boguniewicz²,

Howell³

et al. 2004

J. Clin. Invest.

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482

574

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Atopic dermatitis is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental triggers and is often the first step in the atopic march that results in asthma and allergic rhinitis. The clinical phenotype that characterizes atopic dermatitis is the product of interactions between susceptibility genes, the environment, defective skin barrier function, and immunologic responses. This review summarizes recent progress in our understanding of the pathophysiology of atopic dermatitis and the implications for new management strategies. Historical perspectiveAtopic dermatitis (AD) is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental triggers that are innocuous to normal nonatopic individuals (1). Although written descriptions of AD date back to the early 1800s, an objective laboratory test does not exist for AD. The diagnosis of AD is based on the following constellation of clinical findings: pruritus, facial and extensor eczema in infants and children, flexural eczema in adults, and chronicity of the dermatitis.AD usually presents during early infancy and childhood, but it can persist into or start in adulthood (2). The lifetime prevalence of AD is 10-20% in children and 1-3% in adults. Its prevalence has increased two-to threefold during the past three decades in industrialized countries but remains much lower in countries with predominantly rural or agricultural areas. Wide variations in prevalence have been observed within countries inhabited by groups with similar genetic backgrounds, suggesting that environmental factors play a critical role in determining expression of AD.A precise understanding of the mechanisms underlying AD is critical for development of more effective management strategies (Table 1). Various studies indicate that AD has a complex etiology, with activation of multiple immunologic and inflammatory pathways (3). The clinical phenotype that characterizes AD is the product of complex interactions among susceptibility genes, the host's environment, defects in skin barrier function, and systemic and local immunologic responses. An understanding of the relative role of these factors in the pathogenesis of AD has been made possible by a variety of approaches, including the analysis of cellular and cytokine gene expression in AD skin lesions in humans as well as gene knockout and transgenic mouse models of candidate genes in AD. The current review will summarize progress in our understanding of the pathophysiology of AD and implications for therapy. Atopy as a systemic diseaseSeveral observations suggest that AD is the cutaneous manifestation of a systemic disorder that also gives rise to asthma, food allergy, and allergic rhinitis (1, 2). These conditions are all characterized by elevated serum IgE levels and peripheral eosinophilia. AD is often the initial step in the so-called "atopic march," which leads to asthma and allergic rhinitis in the majority of afflicted patients. In experimental models of AD, the induction...

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Section: New Approaches To Modulate Atopic Inflammationmentioning

confidence: 95%

New insights into atopic dermatitis

Leung¹,

Boguniewicz²,

Howell³

et al. 2004

J. Clin. Invest.

Self Cite

482

574

View full text Add to dashboard Cite

show abstract

“…Serum IgE became undetectable, FcεRI expression was markedly reduced on basophils (within weeks) as a function of IgE levels, on mast cells (within months) and on dendritic cells [45]. Noticeably, Omalizumab treatment markedly increased the sensitivity threshold in peanut-allergic patients [46].…”

Section: Anti-ige Therapymentioning

confidence: 98%

Regulation of allergy by Fc receptors

Bruhns

Frémont

Daëron

2005

Current Opinion in Immunology

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SummaryThe aggregation of high-affinity IgE receptors (FcεRI) on mast cells and basophils has long been known to be the critical event that initiates allergic reactions. Monomeric IgE was recently found to induce a variety of effects when binding to FcεRI. Up-regulation of FcεRI required binding only, whereas other responses resulted from FcεRI aggregation. Interestingly, FcεRI aggregation has been understood to generate a mixture of positive and negative intracellular signals. Mast cells/basophils express also low-affinity and, under specific conditions, high-affinity IgG receptors. When co-engaging these receptors with FcεRI, IgG antibodies can amplify or dampen IgE-induced mast cell activation. Based on these findings, FcRs have been proposed to be used as targets and/or tools for new therapeutic approaches of allergies.

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“…This idea was based on the premise that foodspecific IgE plays a critical role in IgE-mediated food allergy (but not in non-IgE mediated reactions, such as celiac disease or eosinophilic esophagitis) [17], and if neutralized, might allow oral desensitization to occur more safely, rapidly and effectively. Previous studies provided additional support for such an approach: treatment with anti-IgE mAbs, TNX 901 or omalizumab increased the threshold peanut protein dose for eliciting allergic reactions during an oral food challenge [18][19][20]. These studies, however, focused on the therapeutic goal of limiting allergic reactions that might occur with accidental food ingestion, rather than on facilitating oral desensitization to ultimately obviate reactions on unrestricted diets.…”

Section: Targeting Igementioning

confidence: 99%

Targeting IgE to facilitate oral immunotherapy for food allergy: a potential new role for anti-IgE therapy?

Umetsu¹

2014

Expert Review of Clinical Immunology

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Effect of Anti-IgE Therapy in Patients with Peanut Allergy

Cited by 616 publications

References 30 publications

New insights into atopic dermatitis

New insights into atopic dermatitis

Regulation of allergy by Fc receptors

Targeting IgE to facilitate oral immunotherapy for food allergy: a potential new role for anti-IgE therapy?

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