A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy.
Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetus mediates fetal or neonatal alloimmune thrombocytopenia (FNAIT). Because antibody titer or isotype does not strictly correlate with disease severity, we investigated by mass spectrometry variations in the glycosylation at Asn297 in the IgG Fc because the composition of this glycan can be highly variable, affecting binding to phagocyte IgG-Fc receptors (FcγR). We found markedly decreased levels of core fucosylation of anti-HPA-1a-specific IgG1 from FNAIT patients (n = 48), but not in total serum IgG1. Antibodies with a low amount of fucose displayed higher binding affinity to FcγRIIIa and FcγRIIIb, but not to FcγRIIa, compared with antibodies with a high amount of Fc fucose. Consequently, these antibodies with a low amount of Fc fucose showed enhanced phagocytosis of platelets using FcγRIIIb(+) polymorphonuclear cells or FcγRIIIa(+) monocytes as effector cells, but not with FcγRIIIa(-) monocytes. In addition, the degree of anti-HPA-1a fucosylation correlated positively with the neonatal platelet counts in FNAIT, and negatively to the clinical disease severity. In contrast to the FNAIT patients, no changes in core fucosylation were observed for anti-HLA antibodies in refractory thrombocytopenia (post platelet transfusion), indicating that the level of fucosylation may be antigen dependent and/or related to the immune milieu defined by pregnancy.
Department of Experimental Immunohematology and.
Rick
R
Kapur
Iwan
I
Kustiawan
Anne
A
Vestrheim
Carolien A M
CA
Koeleman
Remco
R
Visser
Helga K
HK
Einarsdottir
Leendert
L
Porcelijn
Dave
D
Jackson
Belinda
B
Kumpel
André M
AM
Deelder
Dennis
D
Blank
Björn
B
Skogen
Mette Kjaer
MK
Killie
Terje E
TE
Michaelsen
Masja
M
de Haas
Theo
T
Rispens
C Ellen
CE
van der Schoot
Manfred
M
Wuhrer
Gestur
G
Vidarsson
D000911:Antibodies, Monoclonal / Q000737:chemistry; D001216:Asparagine / Q000737:chemistry; D001792:Blood Platelets / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D005643:Fucose / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D006031:Glycosylation; D006680:HLA Antigens / Q000737:chemistry; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000097:blood / Q000737:chemistry*; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry*; D007518:Isoantibodies / Q000097:blood / Q000737:chemistry*; D013058:Mass Spectrometry; D009000:Monocytes / Q000166:cytology; D010976:Platelet Count; D049590:Postpartum Period; D011247:Pregnancy; D011994:Recombinant Proteins / Q000737:chemistry; D020349:Surface Plasmon Resonance; D054098:Thrombocytopenia, Neonatal Alloimmune / Q000097:blood* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007518:Isoantibodies; D011994:Recombinant Proteins; D005643:Fucose; D001216:Asparagine; D005947:Glucose