Intravenous immunoglobulin G (IVIg): Properties of dimeric and sialylated IgG

This thesis describes the properties of the IgG dimer and sialylated IgG fraction in IVIg. Both fractions have been suggested to contribute to the immune modulating effects of IVIg in the treatment of autoimmune and inflammatory diseases. Taken together we can conclude that the IgG dimer fraction is heterogeneous. At least three qualitatively different IgG dimer types can be distinguished based on their stability. The relative content of these distinct IgG dimers appears to depend on the IVIg manufacturing process. The presence of IgG dimers in IVIg has been associated with unwanted neutrophil activation during IVIg administration. We found that the current neutrophil activation assay protocol needs to be adapted to prevent IgG coating to the solid phase. To elucidate the role of sialylated IgG in IVIg we measured the degree of IgG sialylation in IVIg. Our results show that the different commercially available IVIg products contain similar amounts of sialylated IgG. In vivo, IVIg-SA (+) showed no enhanced protective effect in our model system. This suggests that an enhanced efficacy of IVIg-SA (+) is not a general property, but possibly varies between model systems. Further research is required to determine the biological relevance of the different IgG dimers types as well as the effects of sialylated IgG as immune modulating fraction in IVIg.