Immunoglobulin Research

Humoral Immune responses to blood cells and IgG Glycosylation 

Most immune-mediated blood cell diseases, including fetal/neonatal alloimmune cytopenias, involve antibody-driven cell destruction. We study B cells, antibody characteristics (including FcγR and complement activation), and IgG interaction with the neonatal Fc-receptor (FcRn), which impacts antibody half-life and transport. Recently, our focus has shifted to IgG glycosylation: our research shows that glycosylation patterns in disease-specific antibodies differ from those in total plasma IgG, influencing disease pathology.
By analyzing Fc-glycosylation of IgG1 alloantibodies formed during pregnancy (against antigens like HPA-1 and RhD) via mass spectrometry—with prof Wuhrer's team at Leiden University—we observed reduced core-fucosylation and increased galactosylation and sialylation. Since Fc-core-fucosylation affects FcγR binding, these changes alter antibody effector function and can affect disease severity. Our glycoengineering work indicates that galactosylation impacts complement activation by changing antibody hexamerization. We continue collaborations with the teams of prof Wuhrer, but also that of Albert Heck at Utrecht University.

Origin of Altered Glycosylation

Our studies reveal that human IgG is typically ~94% fucosylated, but responses to non-enveloped viruses tend to be less fucosylated. We hypothesize that afucosylated immune responses are tailored to combat enveloped viruses. Recent findings suggest enhanced afucosylation in natural immunity to malaria (Plasmodium falciparum), implying that immune responses after transfusion or pregnancy resemble responses to infected blood cells. These responses boost myeloid and NK-cell activity, which may be key to effective malaria protection—unlike current vaccines, which induce fully fucosylated IgG.

Neonatal Fc Receptor Biology

FcRn biology is central to our research, especially regarding antibody half-life and transport. IVIg therapies and drugs targeting FcRn can shorten IgG half-life, benefiting patients with auto- and allo-immune diseases. We have extensively studied how FcRn prolongs IgG life, its subclass preferences, and its non-classical roles in immune cells.

Translating Discoveries to Diagnostics and Therapies

Antibody glycosylation holds promise for diagnostics and risk assessment; identifying unique glycosylation features may inform patient management. Modifying glycosylation could also improve antibody therapies or lead to new treatments, which we intend to explore further.