Publications by authors named "C R Bebbington"
Siglecs (sialic acid-binding immunoglobulin-like lectins) are single-pass cell surface receptors that have inhibitory activities on immune cells. Among these, Siglec-8 is a CD33-related family member selectively expressed on human mast cells and eosinophils, and at low levels on basophils. These cells can participate in inflammatory responses by releasing mediators that attract or activate other cells, contributing to the pathogenesis of allergic and non-allergic diseases.
View Article and Find Full Text PDFIn addition to their well characterized role in mediating IgE-dependent allergic diseases, aberrant accumulation and activation of mast cells (MCs) is associated with many non-allergic inflammatory diseases, whereby their activation is likely triggered by non-IgE stimuli (e.g., IL-33).
View Article and Find Full Text PDFAberrant accumulation and activation of eosinophils and potentially mast cells (MCs) contribute to the pathogenesis of eosinophilic gastrointestinal diseases (EGIDs), including eosinophilic esophagitis (EoE), gastritis (EG), and gastroenteritis (EGE). Current treatment options, such as diet restriction and corticosteroids, have limited efficacy and are often inappropriate for chronic use. One promising new approach is to deplete eosinophils and inhibit MCs with a monoclonal antibody (mAb) against sialic acid-binding immunoglobulin-like lectin 8 (Siglec-8), an inhibitory receptor selectively expressed on MCs and eosinophils.
View Article and Find Full Text PDFArticle Synopsis
- AK002 is a targeted antibody being studied for treating allergic and inflammatory diseases by specifically engaging Siglec-8, which is found on mast cells and eosinophils, leading to their apoptosis and reduced activation.
- The study assessed AK002's effectiveness in various models, showing it binds selectively to relevant cells, induces cell death in activated eosinophils, and enhances immune responses through antibody-dependent cell-mediated cytotoxicity (ADCC).
- Results indicate that AK002 can significantly lower eosinophil levels in human lung tissues and help prevent severe allergic reactions in mouse models, suggesting its potential as a therapeutic option for related diseases.
Background: Sialic acid-binding immunoglobulin-like lectin (Siglec) 8 is selectively expressed on eosinophils, mast cells, and basophils and, when engaged on eosinophils, can cause cell death.
Objective: We sought to characterize surface and soluble Siglec-8 (sSiglec-8) levels in normal donors (NDs) and eosinophilic donors (EOs) and assess the efficacy of anti-Siglec-8 antibodies in inducing eosinophil cell death in vitro.
Methods: Eosinophil expression of Siglec-8 was assessed by using flow cytometry and quantitative PCR.