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 with an antibody, Siglec-8 can induce apoptosis of activated eosinophils and inhibit mast cell activation. AK002 is a humanized, non-fucosylated IgG1 anti-Siglec-8 antibody undergoing clinical investigation for treatment of allergic, inflammatory, and proliferative diseases. Here we examine the human tissue selectivity of AK002 and evaluate the in vitro, ex vivo, and in vivo activity of AK002 on eosinophils and mast cells. METHODS:The affinity of AK002 for Siglec-8 and CD16 was determined by biolayer interferometry. Ex vivo activity of AK002 on human eosinophils from blood and dissociated human tissue was tested in apoptosis and antibody-dependent cell-mediated cytotoxicity (ADCC) assays. The in vivo activity of a murine precursor of AK002 (mAK002) was tested in a passive systemic anaphylaxis (PSA) humanized mouse model. RESULTS:AK002 bound selectively to mast cells, eosinophils and, at a lower level, to basophils in human blood and tissue and not to other cell types examined. AK002 induced apoptosis of interleukin-5-activated blood eosinophils and demonstrated potent ADCC activity against blood eosinophils in the presence of natural killer cells. AK002 also significantly reduced eosinophils in dissociated human lung tissue. Furthermore, mAK002 prevented PSA in humanized mice through mast cell inhibition. CONCLUSION:AK002 selectively evokes potent apoptotic and ADCC activity against eosinophils and prevents systemic anaphylaxis through mast cell inhibition.
journal_name
Int Arch Allergy Immunoljournal_title
International archives of allergy and immunologyauthors
Youngblood BA,Brock EC,Leung J,Falahati R,Bryce PJ,Bright J,Williams J,Shultz LD,Greiner DL,Brehm MA,Bebbington C,Tomasevic Ndoi
10.1159/000501637subject
Has Abstractpub_date
2019-01-01 00:00:00pages
91-102issue
2eissn
1018-2438issn
1423-0097pii
000501637journal_volume
180pub_type
杂志文章abstract:BACKGROUND:T cells are key regulators of immunologic disease parameters. However, their contribution to the process of tissue remodeling is ill defined. In the present study, we investigated gene expression of allergy-characteristic, IL-4-rich T cell cDNAs to monitor expression of genes that might participate in the pa...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000072139
更新日期:2003-08-01 00:00:00
abstract:BACKGROUND:It has been shown that antigen presentation by resting B cells can induce tolerance to intravenously administered protein antigens, but the role of resting B cells in the induction of oral tolerance is unclear. METHODS:Mice continuously treated since birth with rabbit anti-mouse IgM serum for 5 weeks were d...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000024394
更新日期:2000-07-01 00:00:00
abstract:BACKGROUND:Subcutaneous immunotherapy for respiratory allergy has shown a long lasting efficacy after its discontinuation, whereas evidence in the case of sublingual immunotherapy (SLIT) is weak. This retrospective study evaluates whether SLIT exerts a long-lasting effect and whether it relates to its duration. METHOD...
journal_title:International archives of allergy and immunology
pub_type: 临床试验,杂志文章
doi:10.1159/000096001
更新日期:2007-01-01 00:00:00
abstract::Kimura disease is a rare disorder of unknown etiology, characterized by the presence of benign subcutaneous granuloma, marked peripheral blood eosinophilia and elevation of the immunglobulin E (IgE) serum level. Here, we present a case of a 12-year-old boy with Kimura disease who had a history of repeated severe influ...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000337777
更新日期:2012-01-01 00:00:00
abstract::A prospective study was conducted on 73 allergic patients and 14 normal volunteers in order to measure the IgE concentration in both serum and saliva, and analyze salivary IgE according to the characteristics of the allergic disease. IgE was more frequently detected in saliva from allergic patients than from normal su...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000236715
更新日期:1994-05-01 00:00:00
abstract:BACKGROUND:Exposure to Aspergillus fumigatus allergens results in the sensitization and the development of allergic bronchopulmonary aspergillosis in susceptible individuals. Aspergillus antigen consists of a number of chemically diverse components and their cumulative or synergistic effect may result in disease. When ...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000065882
更新日期:2002-10-01 00:00:00
abstract::Because of a unique combination of challenges facing human immunodeficiency virus vaccine developers, a number of traditional and novel vaccine designs are being evaluated essentially in parallel. Monomeric proteins, poxvirus vectors, peptides, and particle-based candidate vaccines have entered or will soon enter huma...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章,评审
doi:10.1159/000237173
更新日期:1995-12-01 00:00:00
abstract::Thioredoxin (TRX) is a redox-active protein that regulates reactive oxidative metabolism and plays a crucial role in the antioxidant system in regulating the reduction/oxidation balance by scavenging reactive oxygen species, which is implicated in the mechanism of asthma. As for the mechanisms by which TRX exerts its ...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章,评审
doi:10.1159/000327501
更新日期:2011-01-01 00:00:00
abstract::Eosinophils used to be thought of as regulators of allergic inflammation, but there is now evidence to the contrary; eosinophils have been found to be the major effector cells responsible for the late asthmatic response (LAR), airway hyperresponsiveness (AHR) and, at least in part, airway remodeling by releasing leuko...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000053829
更新日期:2001-08-01 00:00:00
abstract:BACKGROUND:Anti-inflammatory therapy is a logical approach to slowing the inevitable lung function deterioration in cystic fibrosis (CF) patients. This study's aim was to evaluate inflammatory markers and disease progression in paediatric CF patients chronically treated with azithromycin or low-dose prednisolone. METH...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000453451
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Activated eosinophils are thought to play an important role in allergic inflammation. Prior reports suggest that eosinophils have receptors recognizing IgA, IgG and IgE; however, little is known regarding the direct effects of antigens and antigen-specific immunoglobulins on the functions of eosinophils. ME...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000320226
更新日期:2011-01-01 00:00:00
abstract::Partially purified commercial phospholipase D (PLD) was fractionated by dye-ligand affinity chromatography and nondenaturing polyacrylamide gel electrophoresis (PAGE). Active material migrated as three bands on SDS-PAGE. The two higher-abundance species were shown to have identical N-terminal sequences, while the thir...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000236934
更新日期:1995-05-01 00:00:00
abstract:BACKGROUND:The presence of autoantibodies reacting with the high affinity IgE receptor (FcepsilonRIalpha) usually indicates a more severe form of chronic urticaria (CU). Previously, we showed an increased lymphocyte reactivity in CU patients; however, the relation between enhanced cellular immunity and the presence of ...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000073719
更新日期:2003-10-01 00:00:00
abstract:BACKGROUND:Severe asthma is a heterogeneous disease, which is characterized by airway damage and remodeling. All triggers of asthma, such as allergens, bacteria, viruses, and pollutants, interact with the airway epithelial cells, which drive the airway inflammatory response through the release of cytokines, particularl...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000486314
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Previous studies have shown a negative association between ACP1 *B/*C genotype and total IgE level. ACP1 (acid phosphatase locus 1) is a polymorphic phosphotyrosine phosphatase that interacts with IL4-RA and is involved in T cell receptor signaling. METHODS:In the present paper, we have studied the relation...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000107466
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:We have previously shown that the allergic sensitization to ovalbumin does not represent a superantigen-like immune response. In gene-targeted mice (ΔD-iD) with a single modified Diversity gene segment (D(H)) of the immunoglobulin heavy chain, enriched for charged amino acids, the asthma phenotype in a murin...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000323527
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:The precise roles of T helper (Th)1-type and Th2-type cytokine responses in nickel (Ni)-induced allergic contact dermatitis have not yet been clearly defined. We investigated the involvement of Th2 cytokines in Ni-induced contact hypersensitivity reaction using GATA-3 transgenic (Tg) mice. METHODS:A Ni-tita...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000314372
更新日期:2010-01-01 00:00:00
abstract::The last decade has seen the rapid development of research investigating the mechanisms of apoptosis in a variety of experimental systems. Among the multitude of changes observed in apoptotic cells, chromatin cleavage is considered a biochemical hallmark of apoptosis. Chromatin fragmentation is an enzymatic process wh...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章,评审
doi:10.1159/000236778
更新日期:1994-12-01 00:00:00
abstract::The peripheral blood mononuclear cells (PBMC) from humans allergic to grass pollens (GR+ subjects) show strong in vitro proliferative responses to purified allergens from Lolium perenne pollen Lol p 1, and to a lesser extent to Lol p 2 and Lol p 3. By contrast, PBMC from grass allergic patients undergoing immunotherap...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000237452
更新日期:1997-02-01 00:00:00
abstract::The gut mucosa plays an important role in the induction of oral tolerance. Extending previous observations, we have here shown that serum containing gut-absorbed gliadin induces suppression of the specific systemic immune response in recipient mice parenterally immunized with gliadin. Graft-versus-host reaction (GvHR)...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000237230
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND:Severe refractory atopic dermatitis (AD) is a chronic, debilitating condition that is associated with elevated serum immunoglobulin E (IgE) levels. Thymic stromal lymphopoietin (TSLP), thymus and activation-regulated chemokine (TARC) and OX40 ligand (OX40L) are important immunologic factors involved in the p...
journal_title:International archives of allergy and immunology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1159/000350486
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:House dust mite (HDM)-sensitive allergic rhinitis is a perennial rhinitis with persistent nasal inflammation. Currently, there are no reliable parameters to monitor the severity of perennial allergic rhinitis. The purpose of this study was to evaluate correlations between clinical and laboratory parameters i...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000073266
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND:Elicitation of contact hypersensitivity requires antigen-specific immunoglobulin M (IgM) antibodies that trigger recruitment of effector T cells to the local tissue. These antigen-specific IgM antibodies are produced by B-1-like 'initiator B cells'. In this study, we compared susceptibility to hapten-induced...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000350367
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:The aetiological factors underlying the worldwide increase in the prevalence of asthma and the international patterns of the prevalence of asthma are not well understood. This has led to consideration of factors such as fetomaternal health which may programme the initial susceptibility to allergic sensitisat...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000024149
更新日期:1999-02-01 00:00:00
abstract::We report a clinical study comparing the skin test reactivity to recombinant Aspergillus fumigatus allergen 1 (rAsp fI/a) in patients with atopic dermatitis and A. fumigatus sensitisation (n = 15), A. fumigatus-allergic patients with asthma (n = 10) and healthy control subjects (n = 10). All patients sensitised to A. ...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000237123
更新日期:1995-09-01 00:00:00
abstract:BACKGROUND:The allergenic potential of chicken egg white ovomucoid (OVM) is thought to depend on its stability to heat treatment and digestion. Pepsin-digested fragments have been speculated to continue to exert an allergenic potential. OVM was digested in simulated gastric fluid (SGF) to examine the reactivity of the ...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000082581
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:To elucidate the usefulness of antigen-specific immunotherapy based on oral vaccination with an edible part of the plant, we examined the effect of transgenic (Tg) rice seeds expressing an immunodominant fragment of the group 1 antigen of Dermatophagoides pteronyssinus (Der p 1) on a murine model of asthma. ...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000210649
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Despite parallel increases in asthma and obesity prevalence, there is little data on obesity as a risk factor for atopy. The latter is an important phenotype in asthmatic patients. This study investigates the association between asthma traits, atopy and obesity-related markers in Chinese adolescents. METHOD...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000189196
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Cow's milk protein allergy (CMA) is the most common type of food allergy in childhood and exclusion diet is a challenge for patients. OBJECTIVE:The study aim was to investigate the frequency of tolerance to baked foods containing milk and evaluate immediate skin prick test (SPT) and specific IgEs for diff...
journal_title:International archives of allergy and immunology
pub_type: 新闻
doi:10.1159/000511148
更新日期:2020-10-14 00:00:00
abstract::Reversible airway obstruction and airway inflammation following allergen exposure represent crucial pathophysiological features of allergic asthma. In order to investigate these events, bronchial-specific challenge is commonly employed although it may be complicated and may not be free of possible risks. Therefore, we...
journal_title:International archives of allergy and immunology
pub_type: 杂志文章
doi:10.1159/000237461
更新日期:1997-03-01 00:00:00