Inflammatory bowel diseases (IBDs) comprise a large spectrum of chronic pathologies. Crohn's disease (CD) and ulcerative colitis (UC) are distinct diseases characterized by inflammation of the gastrointestinal tract, which leads to an increased risk of colorectal cancer and a significant reduction in the quality of life in affected individuals. Over the past decade, IBD has become a global burden. While the administration of monoclonal antibodies targeting pro-inflammatory mediators and intestinal homing molecules has reshaped the outlook for IBD treatment, the severe adverse effects observed in certain patient cohorts and the high rates of primary or secondary resistance highlight the need for alternative therapeutic approaches.
To date, there is no available gold standard as a diagnostic tool, and a defined group of patients with IBD remains unclassified. There is an urgent need to deepen the current understanding of the underlying pathophysiological mechanisms and to adopt new technologies in the field of diagnosis as well as in the field of early prediction, diagnosis, and prognosis biomarker discovery. Some promising new techniques are confocal laser endothelial microscopy and molecular imaging, capable of detecting microscopic changes and providing detailed visualization of the mucosal surface. In addition, the study of epigenetic modifications is emerging as an important area for the pathogenesis and biomarker potential of IBD. In addition, glycosylation biomarkers are rapidly becoming increasingly important, especially when dealing with inflammatory and autoimmune diseases, due to the impact of glycosylation on immunoglobulin G (IgG) and other serum proteins.
Fig.1 Glycans are important for fine-tuning of intestinal processes that ensure homeostatic conditions which, if disrupted, lead to IBD. (Hanić, et al., 2019)
Galactose lectins are a family of soluble glycan-binding proteins that modulate immune cell homeostasis and reprogram innate and adaptive immune responses, acting as molecular models of risk-associated or resolution-associated responses. Altered expression of these lectins has been observed in the gastrointestinal tract in a variety of pathological conditions, including IBD. Most of the extracellular activity of galactose lectins is regulated by the availability of specific N- and O-glycan structures on the surface of immune cells. Through the coordinated action of glycosyltransferases and glycosidases, the programmed remodeling of these glycosylated ligands is tightly controlled by environmental factors, including cytokines, hypoxia, and inflammation-induced factors.
Intestinal inflammation can lead to structural changes that ultimately alter the extent and nature of local and systemic protein glycosylation. Circulating abnormal glycosylated IgG has been identified as a potential disease biomarker in inflammatory diseases. Similarly, alterations in mucin glycosylation have profound implications for the development of intestinal inflammation. Furthermore, mice lacking glycosyltransferases involved in O-glycan biosyntheses, such as core 2 β6-N-acetylglucosaminyltransferase 1 (C2GnT1), its isoform C2GnT3, or β1,3-galactosyltransferase C1GalT1, exhibit increased susceptibility to intestinal inflammation in response to administration of sodium dextran sulfate.
Glycosylation malfunction significantly alters the function of key proteins in the intestinal niche and is associated with the etiology of IBD. CD BioGlyco provides comprehensive glycosylation-related services, including but are not limited to Glycosylation Site-specific Antibody-Drug Conjugate (ADC) Development Platform, Characterization of Glycosylation in Protein Drugs, Characterization of Glycosylation in Fc-Fusion Protein Drugs, and Characterization of Glycosylation in Antibody Drugs. In addition, we provide high-quality customized service including Custom Glycosylation of Antibodies and Custom Glycosylation of Proteins. If you are interested in our services, please contact us for more details without any hesitation.
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