Abstract:
BACKGROUND:Numerous strategies have been proposed for the treatment of peanut allergies, but despite the steady advancement in our understanding of atopic immune responses and the increasing number of deaths each year from peanut anaphylaxis, there is still no safe, effective, specific therapy for the peanut-sensitive individual. Immunotherapy would be safer and more effective if the allergens could be altered to reduce their ability to initiate an allergic reaction without altering their ability to desensitize the allergic patient. METHODS:The cDNA clones for three major peanut allergens, Ara h 1, Ara h 2, and Ara h 3, have been cloned and characterized. The IgE-binding epitopes of each of these allergens have been determined and amino acids critical to each epitope identified. Site-directed mutagenesis of the allergen cDNA clones, followed by recombinant production of the modified allergen, provided the reagents necessary to test our hypothesis that hypoallergenic proteins are effective immunotherapeutic reagents for treating peanut-sensitive patients. Modified peanut allergens were subjected to immunoblot analysis using peanut-positive patient sera IgE, T cell proliferation assays, and tested in a murine model of peanut anaphylaxis. RESULTS:In general, the modified allergens were poor competitors for binding of peanut-specific IgE when compared to their wild-type counterpart. The modified allergens demonstrated a greatly reduced IgE-binding capacity when individual patient serum IgE was compared to the binding capacity of the wild-type allergens. In addition, while there was considerable variability between patients, the modified allergens retained the ability to stimulate T cell proliferation. CONCLUSIONS:These modified allergen genes and proteins should provide a safe immunotherapeutic agent for the treatment of peanut allergy.
journal_name
Int Arch Allergy Immunoljournal_title
International archives of allergy and immunologyauthors
Bannon GA,Cockrell G,Connaughton C,West CM,Helm R,Stanley JS,King N,Rabjohn P,Sampson HA,Burks AWdoi
10.1159/000053672keywords:
subject
Has Abstractpub_date
2001-01-01 00:00:00pages
70-2issue
1-3eissn
1018-2438issn
1423-0097pii
53672journal_volume
124pub_type
杂志文章abstract::In contrast to mast cells and basophils, the high affinity IgE receptor (FcepsilonRI) on antigen-presenting cells (APC) shows structural and functional differences. It consists only of a minimal structure of one alpha- and two gamma-chains and enables APC to efficiently take up and present antigen in IgE-mediated dela...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章,评审
doi:10.1159/000053662
更新日期:2001-01-01 00:00:00
abstract::Recent data suggest that stem cell factor (SCF or c-kit ligand, KL) is a major regulator of human mast cells (MCs). In the present study, MCs derived from the lung (n = 8), uterus (n = 14) and heart (n = 4) were analyzed for expression of c-kit receptor and for responses to recombinant SCF. MCs of all organs tested we...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000236568
更新日期:1993-01-01 00:00:00
abstract:INTRODUCTION:Pathologic accumulation and activation of mast cells and eosinophils are implicated in allergic and inflammatory diseases. Sialic acid-binding immunoglobulin-like lectin (Siglec)-8 is an inhibitory receptor selectively expressed on mast cells, eosinophils and, at a lower extent, basophils. When engaged wit...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
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abstract:BACKGROUND:A role of bacterial superantigens in several chronic inflammatory diseases has previously been proposed. Many of these diseases are associated with an imbalance of the T helper cell subsets and their cytokine production. METHODS:Peripheral blood mononuclear cells from healthy donors were incubated with vari...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000024320
更新日期:2000-03-01 00:00:00
abstract::Cross-linking of FcepsilonRI on mast cells elicits positive signal transduction cascades that lead to the release of a variety of proinflammatory mediators. Mouse mast cells also express gp49B1 on their surface, an immunoglobulin superfamily member that bears two immunoreceptor tyrosine-based inhibitory motifs in its ...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000024059
更新日期:1999-02-01 00:00:00
abstract:BACKGROUND:Over the past years, dust of green coffee beans has become known to be a relevant cause for occupational type I allergies. Up to now, allergy diagnostics is based on native green coffee bean extract which exhibits insufficient specificity due to interfering substances as well as batch-to-batch variations. No...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000337461
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000327259
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000237199
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND:Although allergy to local anesthetics (LA) is rare, patients often report unwanted reactions after their administration. A history of anaphylaxis or an atypical reaction related to LA is an indication for typing a safe anesthetic for future surgical or dental procedures. AIM:The aim of the study was to dete...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章,随机对照试验
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更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:It has been reported that protein tyrosine phosphorylation is essential for cytokine production in mouse Th1 cells but not in Th2 cells. However, little is known about the difference of signal transduction between human antigen-specific Th1 and Th2 cell clones. METHODS:Purified protein derivative-specific T...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000024028
更新日期:1999-01-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000236006
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Ultra-rush regimens for administering sublingual immunotherapy to patients with allergies are becoming more widespread. We aimed to assess treatment safety for patients with allergic rhinitis with or without asthma caused by Dermatophagoides house dust mites. METHODS:This observational study at 5 Spanish ce...
journal_title:International archives of allergy and immunology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1159/000319211
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:It is assumed that the very late antigen-4 (VLA-4) plays a key role in selective migration and accumulation of eosinophils to the allergic inflammatory focus. The regulatory mechanism for VLA-4 expression is poorly understood, as is its relationship between other adhesion molecules. OBJECTIVE:The aim of the...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000053850
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Sensitivity to the mite Blomia tropicalis is related to asthma in tropical climates, but correlates of sensitivity to B. tropicalis and its relationship to Dermatophagoides pteronyssinus sensitivity have not been widely examined in families with asthma. The main objective of this study was to determine preva...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000070927
更新日期:2003-06-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000024449
更新日期:2000-11-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000236788
更新日期:1994-12-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000064251
更新日期:2002-07-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000237312
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abstract::The role of CD8+ T cells in the regulation of IgE was investigated by in vivo CD8+ T-cell depletion. Following intraperitoneal immunization with ovalbumin (OVA), OVA-specific T cell responses were first detected in the draining lymph nodes (LN) and subsequently in the spleen. In vitro depletion of LN CD8+ cells reduce...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000237534
更新日期:1997-05-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000237394
更新日期:1996-12-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000076384
更新日期:2004-02-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000077356
更新日期:2004-04-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000237375
更新日期:1996-11-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000063860
更新日期:2002-08-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000346545
更新日期:2013-01-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000095290
更新日期:2006-01-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000496744
更新日期:2019-01-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000321200
更新日期:2011-01-01 00:00:00
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journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000024367
更新日期:2000-06-01 00:00:00