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

Abstract

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 < 1.7 × 10-3 and p < 2 × 10-4, respectively). Neither baseline nor longitudinal changes in IgG-Fc glycosylation after rituximab were associated with clinical treatment response. We conclude that IgG-Fc glycosylation in refractory ITP is similar to healthy controls and does not predict treatment responses to rituximab. The observed changes two months after treatment suggest that rituximab may influence total serum IgG-Fc glycosylation. Overall, our study suggests that the pathophysiology of refractory ITP may differ from other autoimmune diseases.

• Authors: David E Schmidt, Noortje de Haan, Myrthe E Sonneveld, Leendert Porcelijn, C Ellen van der Schoot, Masja de Haas, Jaap-Jan Zwaginga, Manfred Wuhrer, Gestur Vidarsson
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 3051 (02 20 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32080262 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin Fc Fragments
• Immunoglobulin G
• glycosylated IgG
• Rituximab

Topics

• Adult
• Case-Control Studies
• Female
• Humans
• Immunoglobulin Fc Fragments (metabolism)
• Immunoglobulin G (metabolism)
• Male
• Middle Aged
• Purpura, Thrombocytopenic, Idiopathic (drug therapy)
• Rituximab (pharmacology, therapeutic use)