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Sialylation-independent mechanism involved in the amelioration of murine immune thrombocytopenia using intravenous gammaglobulin.

Authors: Leontyev, D  Katsman, Y  Ma, XZ  Miescher, S  Kasermann, F  Branch, DR 
Citation: Leontyev D, etal., Transfusion. 2012 Aug;52(8):1799-805. doi: 10.1111/j.1537-2995.2011.03517.x. Epub 2012 Jan 18.
Pubmed: (View Article at PubMed) PMID:22257295
DOI: Full-text: DOI:10.1111/j.1537-2995.2011.03517.x

BACKGROUND: Sialylation of the N-linked glycan on asparagine-297 within the Fc region of intravenous gammaglobulins (IVIgs) was shown to be necessary for efficacy of IVIg in the amelioration of experimental inflammatory arthritis. To test the role for Fc sialylation of IVIg in immune modulating therapies beyond the K/BxN arthritis model, we examined the efficacy of sialylated compared to nonsialylated IVIg for the ability to attenuate immune thrombocytopenia (ITP) in a mouse model that approximates the clinical setting of human ITP. STUDY DESIGN AND METHODS: We used a published, passive anti-platelet (PLT) dose-escalation mouse model of ITP that approximates clinical ITP. PLT counts were followed over time before and after IVIg treatment. IVIg from two different manufacturers was used to prepare untreated and neuraminidase-treated IVIg. Sambucus nigra agglutinin (SNA) affinity chromatography was used to obtain sialic acid-enriched and -depleted IVIg. Sialic acid content was determined using Western blot, enzyme-linked immunosorbent assay, and high-performance liquid chromatography. RESULTS: Results were the same using sialylated and desialylated (neuraminidase-treated) IVIg from two different manufacturers. No differences were observed between sialic acid-enriched and -depleted IVIg compared to normal IVIg in their efficacy to alleviate ITP. Using quantitative reverse transcription-polymerase chain reaction, no increase in the spleen FcgammaRIIB mRNA was detectable, but a pronounced increase of FcgammaRIIB mRNA in the marrow was seen after IVIg administration. CONCLUSIONS: We conclude that IVIg ameliorates experimental ITP by a mechanism that is independent of sialylation either in the Fc or the Fab region of IVIg.

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CRRD Object Information
CRRD ID: 11344931
Created: 2016-07-08
Species: All species
Last Modified: 2016-07-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.