Thesis Myrthe Sonneveld

Summary

Antibody Fc-glycosylation affects allo- and autoimmunity towards blood cells. Low Fc-fucosylation increases IgG-binding affinity to FcγRIIIa/b, thereby contributing to enhanced cell breakdown and hence, a worse clinical outcome. In this thesis we contribute to the development of new diagnostic assays to predict the severity of alloantibody derived blood diseases like haemolytic disease of the fetus or newborn (HDFN) and fetal or neonatal alloimmune thrombocytopenia (FNAIT) using Fc-glycosylation profiles. We found Fc-fucosylation to be the most important in predicting clinical outcome, followed by galactosylation and sialylation. Next to this, Fc-glycosylation patterns of autoantibody derived diseases like autoimmune haemolytic anemia (AIHA) and immune thrombocytopenia (ITP) were viewed. We found that total IgG1 from patients with RBC-bound antibodies showed significantly decreased galactosylation and sialylation levels compared to healthy controls, similar to what previously has been shown for other autoimmune diseases, but no changes for antigen-specific IgG Fc-glycosylation. We found that antigen-specific antibodies against alloantigens and enveloped viral antibodies show significantly lowered Fc-fucosylation, in contrast to autoantigens, viral antibodies derived after vaccination or non-enveloped viral antibodies which show normal high-level of Fc-fucosylation. This discrepancy could be explained by the immune system reacting differently in allo- and autoimmune diseases, where alloantigens are recognized as foreign membrane antigens in alloimmune diseases, inducing a non-fucosylation immune response.