期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 166, 期 6, 页码 936-945出版社
WILEY-BLACKWELL
DOI: 10.1111/bjh.12965
关键词
haemolytic disease of the fetus and newborn; anti-RhD or anti-D alloantibodies; IgG-glycosylation; IgG-fucosylation
类别
资金
- Sanquin [PPOC-09-025]
- Landsteiner Foundation for Blood Transfusion [1229]
- European Union [278535]
Haemolytic disease of the fetus and newborn (HDFN) may occur when maternal IgG antibodies against red blood cells (RBCs), often anti-RhD (anti-D) antibodies, cross the placenta and mediate the destruction of RBCs via phagocytic IgG-Fc-receptors (Fc gamma R). Clinical severity is not strictly related to titre and is more accurately predicted by the diagnostically-applied monocyte-based antibody-dependent cellular cytotoxicity (ADCC), a sensitive test with relatively low specificity. This suggests that other factors are involved in the pathogenesis of HDFN. Binding of IgG to Fc gamma R requires the N-linked glycan at position 297 in the IgG-Fc-region, consisting of several different glycoforms. We therefore systematically analysed IgG-derived glycopeptides by mass spectrometry from 70 anti-D IgG1 antibodies purified from the plasma of alloimmunized pregnant women. This revealed a variable decrease in Fc-fucosylation in the majority of anti-D IgG1 (even down to 12%), whereas the total IgG of these patients remained highly fucosylated, like in healthy individuals (>90%). The degree of anti-D fucosylation correlated significantly with CD16 (Fc gamma RIIIa)-mediated ADCC, in agreement with increased affinity of defucosylated IgG to human Fc gamma RIIIa. Additionally, low anti-D fucosylation correlated significantly with low fetal-neonatal haemoglobin levels, thus with increased haemolysis, suggesting IgG-fucosylation to be an important pathological feature in HDFN with diagnostic potential.
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