IgG-Fc glycosylation before and after rituximab treatment in immune thrombocytopenia

The interactions of antibodies with myeloid Fcγ receptors and the complement system are regulated by an Asn297-linked glycan in the Fc portion of IgG. Alterations of serum IgG-Fc glycosylation have been reported in various autoimmune diseases, and correlate with treatment response and disease activi...

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Bibliographic Details
Published in:Scientific reports 2020-02, Vol.10 (1), p.3051, Article 3051
Main Authors: Schmidt, David E, de Haan, Noortje, Sonneveld, Myrthe E, Porcelijn, Leendert, van der Schoot, C Ellen, de Haas, Masja, Zwaginga, Jaap-Jan, Wuhrer, Manfred, Vidarsson, Gestur
Format: Article
Language:English
Subjects:
Adult
Autoimmune diseases
Case-Control Studies
CD20 antigen
Complement system
Female
Glycosylation
Humans
Idiopathic thrombocytopenic purpura
Immunoglobulin Fc Fragments - metabolism
Immunoglobulin G
Immunoglobulin G - metabolism
Immunotherapy
Liquid chromatography
Male
Mass spectroscopy
Medicin och hälsovetenskap
Middle Aged
Monoclonal antibodies
Purpura, Thrombocytopenic, Idiopathic - drug therapy
Rituximab
Rituximab - pharmacology
Rituximab - therapeutic use
Thrombocytopenia
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Summary:The interactions of antibodies with myeloid Fcγ receptors and the complement system are regulated by an Asn297-linked glycan in the Fc portion of IgG. Alterations of serum IgG-Fc glycosylation have been reported in various autoimmune diseases, and correlate with treatment response and disease activity. We hypothesized that IgG-Fc glycosylation is altered in immune thrombocytopenia (ITP) and associates with response to anti-CD20 monoclonal antibody treatment (rituximab). IgG-Fc glycosylation was analyzed by liquid chromatography-mass spectrometry. We found that IgG-Fc glycosylation was identical between refractory ITP patients (HOVON64 trial; N = 108) and healthy controls (N = 120). Two months after rituximab treatment, we observed a shift in Fc glycosylation, with a mean 1.7% reduction in galactosylation for IgG1 and IgG4 and a mean 1.5% increase for bisection in IgG1, IgG2/3 and IgG4 (adjusted p 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-59651-7