In this study, the authors enriched IVIg for IgG containing sialic acid ) using Sambucus nigra agglutinin lectin fractionation. In a murine K/N serum transfer model for rheumatoid arthritis they found a 10-fold enhancement of the protective effect of IVIg-SA. By using Fc fragments instead of intact IgG, they demonstrated that sialylated Fc fragments likewise caused an enhanced protection of the mice similar to IVIg-SA. They concluded that the anti-inflammatory activity of IVIg is limited to Fcsialylated IgG molecules. Two years later the same group confirmed the results by showing that a fully recombinant, sialylated IgG1 Fc domain caused a comparable protective effect. The authors extended these findings by showing that SIGNR1 is involved in the binding of sialylated Fc fragments. The abovementioned results of enhanced protection by using sialylated Fc fragments are very convincing,Vorinostat although it is debatable whether the used method is suitable to enrich IVIg for Fc-sialylated IgG. A recent study has demonstrated that the binding of IVIg to SNA lectin is primarily mediated by Fab glycosylation, and that for binding of the Fc part to the SNA lectin column two sialic acid residues are required. Analysis of the glycosylation patterns of IVIg revealed that less than 1% of Fc parts contain two sialic acid residues. An earlier study showed that a sialic acid residue attached to Fc part tends to be hidden within the interface between the two CH2 domains which makes this sialic acid residue inaccessible for SNA lectin binding. They demonstrated that under native conditions SNA lectin binding is restricted to the sialic acid residues attached to the Fab part. SNA lectin bound to the Fc part only under reducing conditions. In the present study we used a murine model of Wortmannin thrombocytopenia to evaluate the effect of IVIg that differed in the amount of sialylated IgG. We demonstrated that enrichment for sialylated IgG did not enhance the efficacy of IVIg. By contrast, the clearance of platelets could only be reduced by administrating IVIg or IVIg-SA. IVIg-SA had no effect on the platelet count. This is in contrast to our hypothesis, which was based on the findings of Kaneko et al. and Anthony et al.. We used the same method as described by Kaneko et al., and our ELISA analysis showed that we enriched for sialylated IgG.