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Low anti‐ R h D I g G ‐ F c‐fucosylation in pregnancy: a new variable predicting severity in haemolytic disease of the fetus and newborn
Author(s) -
Kapur Rick,
Della Valle Luciana,
Sonneveld Myrthe,
Hipgrave Ederveen Agnes,
Visser Remco,
Ligthart Peter,
Haas Masja,
Wuhrer Manfred,
Schoot C. Ellen,
Vidarsson Gestur
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12965
Subject(s) - fucosylation , antibody , antibody dependent cell mediated cytotoxicity , immunoglobulin g , immunology , chemistry , glycan , biology , microbiology and biotechnology , glycoprotein , monoclonal antibody
Summary Haemolytic disease of the fetus and newborn ( HDFN ) may occur when maternal I g G antibodies against red blood cells ( RBC s), often anti‐ R h D (anti‐ D ) antibodies, cross the placenta and mediate the destruction of RBC s via phagocytic I g G ‐ F c‐receptors ( F cγ 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 I g G to F cγ R requires the N ‐linked glycan at position 297 in the I g G ‐ F c‐region, consisting of several different glycoforms. We therefore systematically analysed I g G ‐derived glycopeptides by mass spectrometry from 70 anti‐ D I g G 1 antibodies purified from the plasma of alloimmunized pregnant women. This revealed a variable decrease in F c‐fucosylation in the majority of anti‐ D I g G 1 (even down to 12%), whereas the total I g G of these patients remained highly fucosylated, like in healthy individuals (>90%). The degree of anti‐D fucosylation correlated significantly with CD 16 ( F cγ RIII a)‐mediated ADCC , in agreement with increased affinity of defucosylated I g G to human F cγ RIII a. Additionally, low anti‐ D fucosylation correlated significantly with low fetal‐neonatal haemoglobin levels, thus with increased haemolysis, suggesting I g G ‐fucosylation to be an important pathological feature in HDFN with diagnostic potential.