Abstract
Intravenous immunoglobulin G (IVIg) is widely used against a range of clinical symptoms. For its use in immune modulating therapies such as treatment of immune thrombocytopenic purpura high doses of IVIg are required. It has been suggested that only a fraction of IVIg causes this anti immune modulating effect. Recent studies indicated that this fraction is the Fc-sialylated IgG fraction. The aim of our study was to determine the efficacy of IVIg enriched for sialylated IgG (IVIg-SA (+)) in a murine model of passive immune thrombocytopenia (PIT). We enriched IVIg for sialylated IgG by Sambucus nigra agglutinin (SNA) lectin fractionation and determined the degree of sialylation. Analysis of IVIg-SA (+) using a lectin-based ELISA revealed that we enriched predominantly for Fab-sialylated IgG, whereas we did not find an increase in Fc-sialylated IgG. Mass spectrometric analysis confirmed that Fc sialylation did not change after SNA lectin fractionation. The efficacy of sialylated IgG was measured by administering IVIg or IVIg-SA (+) 24 hours prior to an injection of a rat anti-mouse platelet mAb. We found an 85% decrease in platelet count after injection of an anti-platelet mAb, which was reduced to a 70% decrease by injecting IVIg (p<0.01). In contrast, IVIg-SA (+) had no effect on the platelet count. Serum levels of IVIg and IVIg-SA (+) were similar, ruling out enhanced IgG clearance as a possible explanation. Our results indicate that SNA lectin fractionation is not a suitable method to enrich IVIg for Fc-sialylated IgG. The use of IVIg enriched for Fab-sialylated IgG abolishes the efficacy of IVIg in the murine PIT model.
Highlights
Intravenous immunoglobulin G (IVIg) is a therapeutic immunoglobulin G preparation derived from pooled plasma of at least 1000 healthy blood donors
Our results indicate that Sambucus nigra agglutinin (SNA) lectin fractionation is not a suitable method to enrich IVIg for Fc-sialylated IgG
We demonstrated that enrichment for sialylated IgG did not enhance the efficacy of IVIg
Summary
Intravenous immunoglobulin G (IVIg) is a therapeutic immunoglobulin G preparation derived from pooled plasma of at least 1000 healthy blood donors. It was initially developed as a replacement agent for treating primary and secondary antibody deficiencies. Many patients with acute and chronic autoimmune diseases benefit from IVIg treatment, its use is not in all cases effective [5]. From clinical studies it is known that IVIg therapy is effective in the treatment of antibodydependent thrombocytopenia such as idiopathic thrombocytopenic purpura (ITP) [6,7]. The main protective effect of IVIg in ITP seems to be the inhibition of the Fcc receptor mediated phagocytosis [8,9]. F(ab’) fragments of IVIg are not able to inhibit platelet clearance in a murine model of thrombocytopenia [8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
