In view of the diverse and ubiquitous presence of glycans on all cell surfaces, it is not surprising that several human disease conditions involve acquired changes in glycosylation and/or in the recognition of glycans. In many of the situations, deep investigation of the nature of glycan-receptor interactions could result in improved diagnostic or therapeutic approaches. With rich experience in antibody discovery and glycans studies, experts from Creative Biolabs have launched a cutting-edge glycans antibody development platform. Particularly, we now provide all-around services of anti-glycans antibody discovery and development for a variety of diseases diagnosis and therapy.
Hematology is the branch of medicine associated with the study of the cause, prognosis, treatment, and prevention of diseases associated with blood. These diseases might include hemophilia, blood clots, other bleeding disorders and blood cancers such as leukemia, multiple myeloma, and lymphoma. Glycans represent one of the four main types of essential biological components, along with nucleic acids, proteins, and lipids. Glycans are divided into four subgroups including N-glycans, O-glycans, glycosaminoglycans, and glycosphingolipids. Aberrant glycan production occurs in most hematological malignancies, such as acute myeloid leukemia, myeloproliferative neoplasms, and multiple myeloma, etc. Detailed investigation of aberrant patterns in glycosylation will promote the development of novel, more effective therapeutic strategies targeting hematological malignancies.
Fig.1 Aberrant features of glycan expression in hematological malignancies. (Pang, 2018)
Sickle cell anemia is an inherited disease of hemoglobin that leads to a variety of acute and chronic painful complications. Currently, it is demonstrated that abnormal adhesion of multiple cell types is the main cause and that this is partially mediated by selectins. The selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins. Selectins bind to sugar moieties and are thought to be a type of lectin, cell adhesion proteins that bind sugar polymers. Blocking selectin action with analogs of natural ligands can restore blood flow in a mouse model of sickle cell disease. Such as the pan-selectin inhibitor GMI-1070 displays a significant benefit for patients with acute pain of sickle cell crisis, as it greatly reduced (>80%) their need for intravenous opioid analgesics.
Plasma fibrinogen is sialylated strongly and the sialic acids take part in binding calcium. Certain genetic disorders of fibrinogen are confirmed to be associated with altered sialylation of its N-glycans, which leads to altered function in clotting. Patients with hepatomas and other liver disorders can increase branching and/or number of N-glycans on fibrinogen, causing an overall increase in sialic acid content. Patients with genetic disorders of N-glycan biosynthesis can cause thrombotic or bleeding disorders.
Fig.2 Cellular source of VWF determines its susceptibility for ADAMTS13-mediated proteolysis. (Lenting, 2013)
Autoimmune IgM antibodies can recognize and bind to glycan epitopes that presenting on erythrocytes, which then induces typical cold agglutinin disease. These antibodies mainly recognize the “I” antigen (β1-6-branched poly-N-acetyllactosamine) existing in erythrocytes. Some variants of cold agglutinin disease due to antibodies directly target sialylated N-acetyllactosamines. Besides, some patients with chronic hemodialysis are caused by the formation of anti-sialylated blood group antigen N antibodies.
In this disorder, a subset of bone marrow-derived blood cells express the Tn antigen (O-linked N-acetylgalactosamine, GalNAcα-O-Ser/Thr) and sialyl-Tn (Siaα2-6GalNAcα-O-Ser/Thr) can be recognized by anti-Tn antibodies that present in most normal humans. The underlying cause is a somatic stem cell-based loss of expression of the O-glycan core-1 β1-3 galactosyltransferase activity.
Fig.3 Biosynthesis of O-glycans. (Häuselmann, 2014)
Evidence revealed that aberrant glycosylation of hematopoietic microenvironment significantly affects the malignant process by interacting with neoplastic cells, the characterization of glycans is essential to diagnose the blood disorders in hematology. Creative Biolabs is professional in tailoring high specific, high-affinity antibodies targeting various glycans. We offer one-stop services from immunogen preparation to antibody production. Based on our excellent cell-based and cell-free expression systems, we could prepare glycan in various advanced technologies to fulfill your blood-related diagnosis. Please feel free to contact us for more details.
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