12 results on '"Chang, Tse Wen"'
Search Results
2. Anti-IgE as a mast cell–stabilizing therapeutic agent.
- Author
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Chang, Tse Wen and Shiung, Yu-Yu
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OBSTRUCTIVE lung diseases ,CHEMICALS ,ASTHMA ,MEDICAL research - Abstract
After nearly 20 years of development, humanized monoclonal anti-IgE antibodies have been shown in about 20 phase II and III clinical trials to be effective and safe in treating allergic asthma, perennial and seasonal allergic rhinitis, and allergic reactions to peanuts. Omalizumab has been approved in the United States, European Union, and several other countries for treating patients 12 years and older with moderate-to-severe allergic asthma. Although anti-IgE is often referred to as an IgE-neutralizing antibody and can block IgE''s binding to high-affinity IgE Fc receptors (FcεRI) on mast cells and basophils, it has multiple immunoregulatory effects. One such effect is that as the result of depleting free IgE, FcεRI on mast cells and basophils is downregulated to less than 5% within a few weeks to a few months of anti-IgE treatment. This renders the mediator-packed inflammatory cells insensitive to allergen stimulation. Hence this therapeutic anti-IgE represents a new class of mast cell–stabilizing agents, reducing FcεRI density on mast cells and basophils and causing them to be insensitive to allergens. This mechanism contrasts with that of cromones, mast cell–stabilizing agents that retard Ca
++ mobilization and the degranulation process, thus deflating the intracellular activation signal triggered by IgE-FcεRI aggregation. [Copyright &y& Elsevier]- Published
- 2006
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3. Down regulation of B cells by immunization with a fusion protein of a self CD20 peptide and a foreign IgG.Fc fragment
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Huang, Janice, Sheu, Jim Jinn Chyuan, Wu, Stanley Chi Shen, and Chang, Tse Wen
- Published
- 2002
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4. Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps.
- Author
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Chen, Jiun-Bo, James, Louisa K., Davies, Anna M., Wu, Yu-Chang Bryan, Rimmer, Joanne, Lund, Valerie J., Chen, Jou-Han, McDonnell, James M., Chan, Yih-Chih, Hutchins, George H., Chang, Tse Wen, Sutton, Brian J., Kariyawasam, Harsha H., and Gould, Hannah J.
- Abstract
Background Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs. Objectives We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions. Methods Labeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE-specific B cells from the nasal polyps of 3 patients with aspirin-exacerbated respiratory disease by using fluorescence-activated cell sorting. Recombinant antibodies with “matched” heavy and light chains were cloned as IgG 1 , and those of high affinity for specific SAEs, assayed by means of ELISA and surface plasmon resonance, were recloned as IgE and antigen-binding fragments. IgE activities were tested in basophil degranulation assays. Results Thirty-seven SAE-specific, IgG- or IgA-expressing B cells were isolated and yielded 6 anti-SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation, and IgG 1 or antigen-binding fragments of each anti-SEE enhanced degranulation by the other anti-SEE. Conclusions SEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SEE IgE in anti-SEE IgE-FcεRI complexes. Anti-SEE IgG 1 s can enhance the activity of anti-SEE IgEs as conventional antibodies through CDRs or simultaneously as conventional antibodies and as “superantibodies” through CDRs and framework regions to SEEs in SEE–anti-SEE IgE-FcεRI complexes. [ABSTRACT FROM AUTHOR]
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- 2017
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5. The potential pharmacologic mechanisms of omalizumab in patients with chronic spontaneous urticaria.
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Chang, Tse Wen, Chen, Christina, Lin, Chien-Jen, Metz, Martin, Church, Martin K., and Maurer, Marcus
- Abstract
In patients given a diagnosis of chronic spontaneous urticaria (CSU), there are no obvious external triggers, and the factors that initiate the clinical symptoms of wheal, flare, and itch arise from within the patient. Most patients with CSU have an autoimmune cause: some patients produce IgE autoantibodies against autoantigens, such as thyroperoxidase or double-stranded DNA, whereas other patients make IgG autoantibodies against FcεRI, IgE, or both, which might chronically activate mast cells and basophils. In the remainder of patients with CSU, the nature of the abnormalities has not yet been identified. Accumulating evidence has shown that IgE, by binding to FcεRI on mast cells without FcεRI cross-linking, can promote the proliferation and survival of mast cells and thus maintain and expand the pool of mast cells. IgE and FcεRI engagement can also decrease the release threshold of mast cells and increase their sensitivity to various stimuli through either FcεRI or other receptors for the degranulation process. Furthermore, IgE-FcεRI engagement potentiates the ability of mast cells to store and synthesize de novo inflammatory mediators and cytokines. Administration of omalizumab, by virtue of its ability to deplete IgE, attenuates the multiple effects of IgE to maintain and enhance mast cell activities and hence reduces the ability of mast cells to manifest inflammatory mechanisms in patients with CSU. [ABSTRACT FROM AUTHOR]
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- 2015
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6. Alleles and isoforms of human membrane-bound IgA1
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Hung, Alfur Fu-Hsin, Chen, Jiun-Bo, and Chang, Tse Wen
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AMINO acids , *ORGANIC acids , *MESSENGER RNA , *AMINO compounds - Abstract
Abstract: In humans, IgA exists as two subclasses, IgA1 and IgA2, which contain distinct α1 and α2 heavy chains, respectively. Both subclasses also have membrane-bound forms (mIgA1 and mIgA2) containing the corresponding mα1 and mα2 heavy chains, which differ from α1 and α2 by an additional “membrane-anchor” peptide segment extending from the CH3 domain of α1 and α2. The membrane-anchor segment has three parts: an extracellular, a transmembrane, and an intracellular segment. The heavy chain mα1 exists in short and long isoforms, referred to as mα1S and mα1L, with the latter containing extra 6 amino acid residues, GSCSVA, at the N-terminus of the extracellular segment (residues 453–458). By studying the genomic and mRNA sequences of mα1 and mα2 from 30 individuals residing in Taiwan, we have found that, in addition to the known mα1 allele, referred to as mα1(456S), mα1 also has a previously unknown allele, referred to as mα1(456C) (GenBank accession no. EU431191). This newly identified allele is present in the donor population at a similar proportion to mα1(456S), and appears to exist only as the long isoform, i.e. mα1L, rather than the short isoform, mα1S. Furthermore, we confirmed that mα2 exists only as the short isoform. Future studies will examine whether these mIgA1 variations affect the regulation of IgA synthesis and whether mIgA1 can provide an antigenic site for the immunological targeting of IgA-expressing B cells. [Copyright &y& Elsevier]
- Published
- 2008
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7. Manipulating mIgD-expressing B cells with anti-migis-δ monoclonal antibodies
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Chen, Nien-Yi, Hung, Alfur Fu-Hsin, Lin, Chien-Jen, Chen, Jiun-Bo, Chu, Hsing-Mao, Yu, Hui-Ming, Chang, Hwan-You, and Chang, Tse-Wen
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IMMUNOGLOBULIN D , *B cells , *MONOCLONAL antibodies , *IMMUNOGLOBULIN M , *IMMUNE system , *BIOLOGICAL membranes - Abstract
Abstract: Surface IgD and IgM doubly positive cells comprise the major population of B cells in the human immune system. The heavy chain of membrane-bound IgD (mδ) differs from that of IgD (δ) in that mδ contains a C-terminal membrane-anchor peptide. Our group previously proposed that the N-terminal extracellular segment of 27 aa residues of the membrane-anchor peptide of mδ, referred to as the mIg isotype-specific-δ (migis-δ) segment, may provide a unique antigenic site for isotype-specific targeting of mIgD+ B cells. Here we report the preparation of mouse mAbs specific for human migis-δ. The mAbs bound to human migis-δ-containing recombinant proteins in an ELISA and to mIgD-expressing transfectants of a CHO cell line as analyzed by flow cytometry. MAb 20E6, which binds to an epitope toward the N-terminal of human migis-δ, could stain human B cell line MC116, which expressed mIgD and mIgM. MC116 cells could be induced to undergo apoptosis by treatment with 20E6 in the presence of a second crosslinking antibody. Chimeric 20E6 caused antibody-dependent cellular cytotoxicity of MC116 cells in the presence of human PBMCs as the source of effector cells. In cultures of PBMCs, 20E6 down-regulated the population of mIgD+ B cells. The production of human IgM by transplanted MC116 cells in NOD-SCID (NOD.CB17-Prkdc scid/IcrCrlBltw) mice could be suppressed by 20E6. These results encourage further investigation of the potential of anti-migis-δ mAbs to control mIgD+ B cells, when such a manipulation may alleviate a disease state. [Copyright &y& Elsevier]
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- 2013
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8. CɛmX peptide-carrying HBcAg virus-like particles induced antibodies that down-regulate mIgE-B lymphocytes
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Lin, Chien-Jen, Chen, Nien-Yi, Chen, Jiun-Bo, Lu, Chien-Sheng, Hung, Alfur Fu-Hsin, Shiung, Yu-Yu, Wu, Pheidias C., Pan, Rong-Long, and Chang, Tse Wen
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VIRUS-like particles , *IMMUNOGLOBULIN E , *B cells , *ALLERGIES , *ANTI-immunoglobulin E autoantibodies , *APOPTOSIS , *LABORATORY mice , *HEPATITIS B , *ANTIBODY-dependent cell cytotoxicity - Abstract
Abstract: Type-I hypersensitivity reactions play a critical role in the pathogenesis of various allergic diseases. The successful development of the anti-IgE antibody, omalizumab, has validated IgE as an effective therapeutic target for the treatment of various IgE-mediated allergic diseases. Two research groups have reported that mAbs specific for certain parts of CɛmX, a domain of 52 aa residues in human membrane-bound IgE (mIgE), can cause the lysis of mIgE-B cells by apoptosis and antibody-dependent cellular cytotoxicity (ADCC). Herein, we explore virus-like particles formed by hepatitis B virus core antigen (HBcAg) that harbors the entire CɛmX peptide or its fragments as immunogens for inducing anti-CɛmX antibodies. The results showed that mice immunized subcutaneously with these immunogens produced antibodies that bind to recombinant CɛmX-containing human IgE.Fc in ELISA and Western blot analyses, and to genetically engineered human mIgE-expressing Ramos B cell line in fluorescence flow cytometric assays. The IgG antibodies purified from the sera of immunized mice were able to cause the apoptosis of mIgE-expressing Ramos cells through a BCR-dependent caspase pathway. Furthermore, the IgG could mediate ADCC in human mIgE-expressing A20 murine B-cell lymphoma. These studies suggest that HBcAg-CɛmX peptide immunogens warrant further investigation as a therapeutic modality for modulating IgE in patients with IgE-mediated allergic diseases. [Copyright &y& Elsevier]
- Published
- 2012
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9. An anti-IgE monoclonal antibody that binds to IgE on CD23 but not on high-affinity IgE.Fc receptors
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Shiung, Yu-Yu, Chiang, Chen-Yi, Chen, Jiun-Bo, Wu, Pheidias C., Hung, Alfur Fu-Hsin, Lu, Donic Chien-Sheng, Pan, Rong-Long, and Chang, Tse Wen
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ANTI-immunoglobulin E autoantibodies , *MONOCLONAL antibodies , *CD23 antigen , *HORSERADISH peroxidase , *ENZYME-linked immunosorbent assay , *FLUORESCEIN isothiocyanate - Abstract
Abstract: A new monoclonal antibody (mAb), specific for human IgE, the central mediator of immediate-type hypersensitivity reactions, has been shown to possess a unique set of binding specificities. The mAb, 8D6, binds to a conformational epitope on the CH3 domain of human e immunoglobulin and can compete with omalizumab for binding to IgE. Like omalizumab, it does not bind to IgE bound by the high-affinity IgE.Fc receptor (FcɛRI) on basophils and mast cells. It also does not cause activation and degranulation of IgE-pulsed, human FcɛRI-expressing rat basophilic leukemic cells (RBL SX-38). The mAb can inhibit IgE binding to recombinant α chain of human FcɛRI in ELISA and to human FcɛRI-expressing RBL SX38 cells in fluorescence flow cytometric analysis. However, unlike omalizumab, 8D6 can bind to IgE already bound by the low-affinity IgE.Fc receptors (FcɛRII, or CD23), as revealed in ELISA with recombinant CD23 and in flow cytometric analysis with human B cells. Since earlier investigators have shown that anti-CD23 mAbs can inhibit the synthesis of IgE in lymphocyte culture in vitro and can down-regulate IgE production in treated patients, 8D6 may offer pharmacological mechanisms in addition to those mediated by omalizumab, for controlling IgE in patients with allergic diseases. [Copyright &y& Elsevier]
- Published
- 2012
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10. Lipid rafts hinder binding of antibodies to the extracellular segment of the membrane-anchor peptide of mIgA
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Hung, Alfur Fu-Hsin, Chen, Jiun-Bo, Lu, Chien-Sheng, Chen, Nien-Yi, Yu, Hui-Ming, and Chang, Tse Wen
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LIPIDS , *PEPTIDES , *IMMUNOGLOBULIN A , *EXTRACELLULAR matrix proteins , *MONOCLONAL antibodies , *GENE expression , *ENZYME-linked immunosorbent assay - Abstract
Abstract: Membrane-bound IgA (mIgA) is associated with Igα/Igβ as the B cell receptor (BCR) complex on mIgA-expressing B cells. The α chain of mIgA (mα) contains a C-terminal membrane-anchor peptide, which encompasses extracellular, transmembrane and intracellular segments. The extracellular segment, referred to as the mIg isotype-specific (migis-α) segment or the extracellular membrane proximal domain of mα, has been proposed to be a specific antigenic site suitable for isotype-specific targeting of mIgA-expressing B cells by antibodies. In this study, we developed several anti-migis-α monoclonal antibodies (mAbs), such as mAb 29C11, specific to a segment towards the N-terminus of the 26 amino acid long migis-α. The mAbs bound strongly to synthetic peptides of migis-α and to various recombinant proteins containing migis-α as revealed by ELISA. On B cells, however, flow cytometric analysis suggested that these mAbs did not bind strongly to mIgA. After lipid rafts of B cells were disrupted by cholesterol extraction, the mAbs were able to bind strongly to the treated B cells. Moreover, immunoprecipitation analysis of these mAbs indicated that mIgA could only be pulled down by the mAbs when mIgA-expressing B cells were solubilized by strong detergents, such as sodium dodecyl sulfate (SDS), or when lipid rafts were disrupted. Together, these results suggest that the migis-α region of mIgA in the BCR is associated with lipid rafts, which hinder binding of migis-α-specific antibodies to mIgA on the cell surface. Further studies are in progress to evaluate the suitability of 29C11 or its affinity-improved variants for targeting mIgA-expressing B cells. [Copyright &y& Elsevier]
- Published
- 2011
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11. Accumulated immune complexes of IgE and omalizumab trap allergens in an in vitro model
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Hsu, Chuan-Long, Shiung, Yu-Yu, Lin, Bai-Ling, Chang, Hwan-You, and Chang, Tse Wen
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IMMUNE complexes , *IMMUNOGLOBULIN E , *THERAPEUTIC use of monoclonal antibodies , *ALLERGENS , *BIOCHEMICAL mechanism of action , *CELL receptors , *MAST cell immunology , *BASOPHILS - Abstract
Abstract: The best understood mechanisms of omalizumab are that it neutralizes free IgE and down-regulates high-affinity IgE.Fc receptors (FcεRI) on basophils and mast cells. It has been proposed that since complexes of IgE and omalizumab are accumulated to 5–10 times the basal levels of IgE, they may trap incoming allergens, contributing to omalizumab''s effectiveness. In order to investigate the ability of IgE:omalizumab complexes in trapping allergens and inhibiting basophil activation in an in vitro reconstitution model, the ability of IgE:omalizumab complexes to tie up antigen and hence inhibit (a) antigen binding to IgE bound by FcεRI, and (b) antigen-mediated activation of basophils, was examined. The free IgE was prepared by mixing different proportions of antigen-nonspecific IgE secreted by U266 cells and antigen-specific IgE, SE44 IgE, which recognizes a synthetic 15 a.a. peptide, R15K. The antigen was (R15K)8-ova, i.e. ovalbumin conjugated with an average of 8 copies of R15K per molecule. The solid-phase FcεRI was a recombinant protein representing the extracellular portion of the α chain of the FcεRI receptor complex. The model FcεRI+ basophilic cell line was RBL.SX-38, a rat basophilic leukemic line transfected with the genes for α, β and γ subunits of human FcεRI. The results showed that the IgE:omalizumab complexes trapped increasing amounts of antigen with increasing (a) concentration of IgE, (b) proportion of antigen-specific IgE in total IgE, and (c) concentration of total immune complexes. Such trapping decreased the antigen-induced activation of FcεRI+ cells that had been pulsed with antigen-specific IgE, resulting in decreased mediator release. These results suggest that the rapidly accumulated IgE:omalizumab complexes in omalizumab-treated patients can capture allergens and consequently contribute to the pharmacological effects of omalizumab. [Copyright &y& Elsevier]
- Published
- 2010
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12. <atl>Down regulation of B cells by immunization with a fusion protein of a self CD20 peptide and a foreign IgG.Fc fragment
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Huang, Janice, Sheu, Jim Jinn Chyuan, Wu, Stanley Chi Shen, and Chang, Tse Wen
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B cells , *CELLULAR control mechanisms , *CD antigens , *PEPTIDES , *IMMUNOGLOBULINS - Abstract
In vivo studies of mice were performed to investigate whether auto-reactive antibodies specific for self CD20 antigen on B cells could be induced by immunizing with a CD20 peptide linked to a foreign, human IgG.Fc fragment through a T cell immunologically inert linker peptide and how such an auto-reactivity, if generated, would affect the levels of B cells. The dimeric Fc fusion protein containing the extracellular 44-amino acid portion of CD20, and the CH2–CH3 domains of human γ1 immunoglobulin were prepared. After several subcutaneous immunizations with this CD20-Fc protein, mice produced anti-CD20 antibodies that can bind to native CD20 on normal B cells and B-lymphoma cells. In mice immunized with the CD20-Fc protein, the fraction of B cells in total peripheral blood lymphocytes decreased to about 40%, significantly lower than that of mice immunized with human IgG. In addition, antibody response towards an irrelevant bystander antigen, chicken ovalbumin, was weakened compared with that of mice immunized with human IgG. These results show that auto-reactive antibodies specific for CD20 can be induced by immunizing with an autologous CD20 peptide fused with a foreign IgG.Fc and that the auto-antibodies can partially reduce the levels of B cells and their response to other antigens. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
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