Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allergen characterisation that is based on patients' sera or monoclonal allergen-specific IgG antibodies has several disadvantages. Current methods such as immunoblotting or allergen-specific EUSA are non-functional assays and cannot be used to evaluate the biological allergenic activity of allergen products. We have established an in vitro assay based on polyclonal murine IgE and allergen-dependent mediator release of rat basophilic leukaemia (RBL) cells as an alternative to passive cutaneous anaphylaxis (PCA), an animal model of IgE-mediated allergic reactions. The RBL assay is a functional in vitro test which enables the measurement of biological potency of allergen extracts to be made. Up to now, allergen-specific IgE-containing murine sera were used for sensitisation of RBL cells. Sensitisation with allergen-specific IgE monoclonal antibodies (IgE mAbs) would reduce the number of animals necessary for the production of allergen-specific IgE. In addition, IgE mAbs are better defined and will offer more exact determination of allergens. Since allergen-specific IgE mAbs were not available, the aim of this study was to produce such antibodies. As a new strategy to select IgE-producing hybridomas the RBL mediator release assay was used: the cells were incubated with hybridoma supernatant and stimulated with allergen and crosslinking allergen-specific polyclonal IgG antibodies. By this technology IgE mAbs specific for the birch pollen allergens Bet v 1 and Bet v 6 were produced. In conclusion, this novel strategy enables the production of panels of allergen-specific IgE mAbs by immunisation of a limited number of mice to be made. These IgE mAbs in combination with the RBL mediator release assay may serve as new tools for the evaluation of diagnostic and therapeutic allergen extracts.
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PMID:Replacement of murine sera by allergen-specific monoclonal IgE antibodies: a new approach for the characterisation of allergen extracts. 1267 30

Type I allergy is characterized by the development of an initial Th2-dependent allergen-specific IgE response, which is boosted upon a subsequent allergen encounter. Although the immediate symptoms of allergy are mainly IgE-mediated, allergen-specific T cell responses contribute to the late phase as well as to the chronic manifestations of allergy. This study investigates the potential of costimulation blockade with CTLA4Ig and an anti-CD154 mAb for modifying the allergic immune response to the major timothy grass pollen allergen Phl p 5 in a mouse model. BALB/c mice were treated with the costimulation blockers at the time of primary sensitization to the Phl p 5 allergen or at the time of a secondary allergen challenge. Costimulation blockade (CTLA4Ig plus anti-CD154 or anti-CD154 alone) at the time of sensitization prevented the development of allergen-specific IgE, IgM, IgG, and IgA responses compared with untreated but sensitized mice. However, costimulation blockade had no influence on established IgE responses in sensitized mice. Immediate-type reactions as analyzed by a rat basophil leukemia cell mediator release assay were only suppressed by early treatment but not by a costimulation blockade after sensitization. CTLA4Ig given alone failed to suppress both the primary and the secondary allergen-specific Ab responses. Allergen-specific T cell activation was suppressed in mice by early as well as by a late costimulation blockade, suggesting that IgE responses in sensitized mice are independent of T cell help. Our results indicate that T cell suppression alone without active immune regulation or a shifting of the Th2/Th1 balance is not sufficient for the treatment of established IgE responses in an allergy.
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PMID:Costimulation blockade inhibits allergic sensitization but does not affect established allergy in a murine model of grass pollen allergy. 1733 93

Allergen-mediated cross-linking of the high-affinity receptor for IgE on mast cells triggers the release of diverse preformed and de novo synthesized immunoregulatory mediators that further the allergic response. A proteomic screen applied to the detection of proteins secreted by the model rat mast cell line, RBL-2H3 (rat basophilic leukaemia, subline 2H3.1), led to the identification of the cholesterol-binding glycoprotein, NPC2/RE1 (Niemann-Pick Type C2/epididymal secretory protein 1). Glycosylated NPC2 is secreted early in response to an IgE-mediated stimulus and co-localizes with the lysosomal membrane marker, CD63. NPC2 belongs to the ML (MD-2-related lipid-recognition) protein family (155 members), which includes the Toll-like receptor co-factors, MD-1 and MD-2, and perhaps most interestingly, seven major house dust mite allergens of unknown function (including Der p 2 and Der f 2). Possible role(s) for the protein in the allergic response and future applications of this approach are discussed.
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PMID:Proteomic identification and characterization of secreted N-glycosylated NPC2 following cross-linking of the high-affinity receptor for IgE on mast cells. 2000 54

Allergen-specific Immunoglobulin E (IgE) determination lies at the heart of diagnosis of sensitization to food and other allergens. In the past few years, reporter systems capable of detecting the presence of allergen-specific IgE have been developed by several labs. These rely on humanized rat basophil leukemia cell lines stably transfected with reporter genes such as firefly luciferase. In this chapter, we describe protocols for the use of the RS-ATL8 cell line (IgE cross-linking-induced luciferase expression; EXiLE) in 96-well and 384-well formats. We also describe optional treatment steps for enveloped virus and complement inactivation.
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PMID:Use of Humanized RS-ATL8 Reporter System for Detection of Allergen-Specific IgE Sensitization in Human Food Allergy. 2831 18