Dataset Information

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

ABSTRACT: The interactions of antibodies with myeloid Fc? 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?

SUBMITTER: Schmidt DE

PROVIDER: S-EPMC7033207 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Schmidt David E DE de Haan Noortje N Sonneveld Myrthe E ME Porcelijn Leendert L van der Schoot C Ellen CE de Haas Masja M Zwaginga Jaap-Jan JJ Wuhrer Manfred M Vidarsson Gestur G

Scientific reports 20200220 1

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 ...[more]

PMID: 32080262

Similar Datasets

Project description:Preterm infants acquire reduced amounts of Immunoglobulin G (IgG) via trans-placental transfer as compared to term infants which might explain their high susceptibility for infections. The reduced amount of IgG antibodies also results in a lower amount of anti-inflammatory Fc N-galactosylated and -sialylated IgG antibodies. This reduction or, even more, a qualitative shift in the type of IgG Fc glycosylation might contribute to the increased risk for sustained inflammatory diseases in preterm infants. It was the aim of our explorative study to investigate the IgG Fc glycosylation patterns in preterm infants of different gestational ages compared to term infants and mothers of preterm infants. In plasma samples of preterm infants (n = 38), we investigated IgG concentrations by use of ELISA. Furthermore, we analyzed IgG Fc glycosylation patterns in plasma of preterm infants (n = 86, 23-34 weeks of gestation), term infants (n = 15) and mothers from preterm infants (n = 41) using high performance liquid chromatography. Extremely low gestational age infants (born < 28 weeks of gestation during second trimester) had reduced IgG concentrations and decreased proportions of galactosylated (84.5 vs. 88.4%), sialylated (14.5 vs. 17.9%) and bisecting N-acetylglucosamine-containing (8.4 vs. 10.8%) IgG Fc N-linked glycans as compared to preterm infants born ?28 weeks of gestation (during third trimester) and term infants. Increased non-galactosylated (agalactosylated, 16.9 vs. 10.6%) IgG Fc N-linked glycans were associated with the development of chronic inflammatory bronchopulmonary dysplasia (BPD). However, mothers of preterm infants born during second or third trimester of pregnancy did not show significant differences in IgG Fc glycosylation patterns. Thus, the IgG Fc glycosylation patterns of preterm infants depend on their gestational age. Although lack of bisecting N-acetylglucosamine has been associated with less inflammatory effector functions, the decreased IgG Fc galactosylation and sialylation with lower gestational age suggest a rather pro-inflammatory pattern. The difference in IgG Fc glycosylation patterns between preterm infants and mothers of preterm infants suggests a selective enrichment of IgG glyco forms in preterm infants, which might contribute to or result of the development of sustained inflammatory diseases like BPD.

Project description:BackgroundRituximab has been widely used off-label as a second line treatment for children with immune thrombocytopenia (ITP). However, its role in the management of pediatric ITP requires clarification. To understand and interpret the available evidence, we conducted a systematic review to assess the efficacy and safety of rituximab for children with ITP.Methodology/principal findingsWe searched MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, abstract databases of American Society of Hematology, American Society of Clinical Oncology and Pediatric Academic Society. Clinical studies published in full text or abstract only in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. Safety was evaluated from all studies that reported data of toxicity. 14 studies (323 patients) were included for efficacy assessment in children with primary ITP. The pooled complete response (platelet count ? 100 × 10(9)/L) and response (platelet count ? 30 × 10(9)/L) rate after rituximab treatment were 39% (95% CI, 30% to 49%) and 68% (95%CI, 58% to 77%), respectively, with median response duration of 12.8 month. 4 studies (29 patients) were included for efficacy assessment in children with secondary ITP. 11 (64.7%) of 17 patients associated with Evans syndrome achieved response. All 6 patients with systemic lupus erythematosus associated ITP and all 6 patients with autoimmune lymphoproliferative syndrome associated ITP achieved response. 91 patients experienced 108 adverse events associated with rituximab, among that, 91 (84.3%) were mild to moderate, and no death was reported.Conclusions/significanceRandomized controlled studies on effect of rituximab for children with ITP are urgently needed, although a series of uncontrolled studies found that rituximab resulted in a good platelet count response both in children with primary and children secondary ITP. Most adverse events associated with rituximab were mild to moderate, and no death was reported.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets