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Enrichment of sialylated IgG by lectin fractionation does not enhance the efficacy of immunoglobulin G in a murine model of immune thrombocytopenia.

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.
AuthorsTheresa Guhr, Judith Bloem, Ninotska I L Derksen, Manfred Wuhrer, Anky H L Koenderman, Rob C Aalberse, Theo Rispens
JournalPloS one (PLoS One) Vol. 6 Issue 6 Pg. e21246 ( 2011) ISSN: 1932-6203 [Electronic] United States
PMID21731683 (Publication Type: Journal Article)
Chemical References
  • Immunoglobulin G
  • Immunoglobulins, Intravenous
  • Plant Lectins
  • Sambucus nigra lectins
  • Ribosome Inactivating Proteins
  • N-Acetylneuraminic Acid
Topics
  • Animals
  • Chemical Fractionation
  • Chromatography, Affinity
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Glycosylation
  • Humans
  • Immunoglobulin G (immunology)
  • Immunoglobulins, Intravenous (administration & dosage, therapeutic use)
  • Immunomodulation (immunology)
  • Mass Spectrometry
  • Mice
  • N-Acetylneuraminic Acid (metabolism)
  • Plant Lectins (metabolism)
  • Platelet Count
  • Purpura, Thrombocytopenic, Idiopathic (drug therapy, immunology)
  • Rats
  • Ribosome Inactivating Proteins (metabolism)

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