Anti‐IgE Antibodies for the Treatment of IgE‐Mediated Allergic Diseases

Chang, Tse Wen; Wu, Pheidias C.; Hsu, Chuan-Long; Hung, Alfur Fu-Hsin

doi:10.1016/s0065-2776(06)93002-8

Cited by 120 publications

(98 citation statements)

References 217 publications

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“…Moreover, we have generated a humanized M1′-specific antibody that is suitable for administration in human asthma and other allergic diseases. Current anti-IgE therapy consists of non-anaphylactogenic IgE-specific antibody that binds and neutralizes the activity of serum IgE (7)(8)(9). This antibody does not affect IgE production (16) and therefore must be administered frequently and chronically in order to maintain sufficient suppression of free serum IgE.…”

Section: Figurementioning

confidence: 99%

“…To quantitate IgE-producing plasma cells and total plasma cells, spleens were harvested at takedown. 8 PBMCs from an atopic human donor. Mice were treated on days 2, 3, and 4 with 100 ng recombinant human IL-4 and on days 0 and 3 with 100 μg each of anti-human IFN-γ and anti-human IL-12 neutralizing antibodies.…”

Section: Tnp-ova Immunization (Primary and Secondary/memory Responses)mentioning

confidence: 99%

“…Elevated serum IgE levels cause the upregulation of IgE receptors on mast cells and basophils, increase the sensitivity of these cells to allergen-triggered activation, and also enhance cell survival (5,6). Therapeutic targeting of serum IgE with a neutralizing, non-anaphylactogenic IgE-specific antibody is an efficacious treatment for moderate-to-severe allergic asthma (7)(8)(9). Neutralization of serum IgE with this IgE-specific antibody desensitizes mast cells and basophils by decreasing surface IgE receptor expression, ultimately leading to decreased exacerbations in asthmatics (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

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Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice

Brightbill¹,

Jeet²,

Lin³

et al. 2010

J. Clin. Invest.

101

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IgE-mediated hypersensitivity is central to the pathogenesis of asthma and other allergic diseases. Although neutralization of serum IgE with IgE-specific antibodies is in general an efficacious treatment for allergic asthma, one limitation of this approach is its lack of effect on IgE production. Here, we have developed a strategy to disrupt IgE production by generating monoclonal antibodies that target a segment of membrane IgE on human IgE-switched B cells that is not present in serum IgE. This segment is known as the M1′ domain, and using genetically modified mice that contain the human M1′ domain inserted into the mouse IgE locus, we demonstrated that M1′-specific antibodies reduced serum IgE and IgE-producing plasma cells in vivo, without affecting other immunoglobulin isotypes. M1′-specific antibodies were effective when delivered prophylactically and therapeutically in mouse models of immunization, allergic asthma, and Nippostrongylus brasiliensis infection, likely by inducing apoptosis of IgE-producing B cells. In addition, we generated a humanized M1′-specific antibody that was active on primary human cells in vivo, as determined by its reduction of serum IgE levels and IgE plasma cell numbers in a human PBMC-SCID mouse model. Thus, targeting of human IgE-producing B cells with apoptosis-inducing M1′-specific antibodies may be a novel treatment for asthma and allergy.

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Section: Figurementioning

confidence: 99%

Section: Tnp-ova Immunization (Primary and Secondary/memory Responses)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice

Brightbill¹,

Jeet²,

Lin³

et al. 2010

J. Clin. Invest.

101

View full text Add to dashboard Cite

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“…В этой связи рекомендуется перед прове-дением лечения сделать точный анализ, позволя-ющий определить истинное значение циркулиру-ющего свободного IgE. При этом уровень общего IgE, превышающий 700 Ме/мл, является противо-показанием для назначения терапии препаратом Omalizumab [23].…”

Section: механизм взаимодействия Ige-антитела с Fcεr-рецеп-торомunclassified

Diagnostic value of serum total IgE the primary marker of allergic diseases

Mokronosova¹

2015

Lab. sluzh.

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Ключевые слова: иммуноглобулин е, IgE-опосредованная патология, анти-IgE терапия.Discovery of immunoglobulin e in 1967-1968 belongs to Johansson sGO and ishizaka K. the concentration of ige in the serum is 0.05% of all immunoglobulins. molecule ige binds to Fcεr receptor on the surface of mast cells and basophils. the triggering of the mast cells's activation due to contact of the ige molecule with the receptor is the basic mechanism of most common allergic reactions characterized by an immediate type hyperreactivity. serum total ige -is an important diagnostic marker which is used to screen for atopic diseases , the diagnosis of helminthiasis and various immune diseases. the level of total immunoglobulins is used as the primary marker when assigning and monitoring the anti-ige therapy.

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“…To put it simply, by binding circulating free IgE, omalizumab prevents mast cell degranulation and downstream mediator effects (2). Since omalizumab has been suggested to be possibly beneficial for management of chronic spontaneous urticaria as well (3)(4)(5), randomized placebo-controlled trials have been carried out to assess efficacy of anti-IgE therapy in chronic spontaneous urticaria (6,7), culminating in its recent approval for this indication both in the U.S. and Europe.…”

Section: Introductionmentioning

confidence: 99%