Fucosylation, or adding a sugar molecule to immunoglobulin G (IgG) antibodies, could help in determining the severity of alloimmune diseases like fetal and neonatal alloimmune thrombocytopenia (FNAIT), according to a recently published study in Glycoscience and Therapy.
FNAIT is caused by maternal IgG that crosses the placental barrier and destroys fetal platelets, producing thrombocytopenia, which is associated with an increased risk of bleeding. Since IgG plays a major role in the disease, it is expected that molecular changes in its structure could have important clinical implications.
What is fucosylation?
Fucosylation is mediated by an enzyme called fucosyltransferase (FUT8), which adds the fucose (sugar) residue to the glycan structure of IgG. This process is influenced by factors such as the immune environment during pregnancy, genetic factors (particularly those involving the gene that encodes the FUT8 enzyme), and pregnancy history. Some studies have observed a significant decrease in fucosylation after the first pregnancy.
Low fucosylation of IGg helps it bind to receptors on immune cells, which ultimately contributes to more platelets being destroyed.
How does fucosylation affect FNAIT?
Research shows that the fucosylation process significantly affects IgG’s ability to bind to FcγRIIIa, a receptor critical for activating immune cells such as natural killer (NK) cells. Some studies suggest that patients with FNAIT and hemolytic disease of the fetus and newborn (HDFN) tend to exhibit reduced IgG core fucosylation.
Low fucosylation in these patients is associated with a stronger immune response, enhanced platelet destruction and a more complicated disease course. Some studies have even found an inverse correlation between the degree of fucosylation and positive outcomes.
“Hence, specific IgG glycosylation features directly influence the clinical efficacy of antibodies, stratify patients by disease severity and identify patients likely to develop a severe clinical phenotype that necessitates treatment,” the authors wrote.
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