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Br J Haematol. 2016 Jul;174(2):310-20. doi: 10.1111/bjh.14053. Epub 2016 Mar 28.

Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia.

Author information

1
Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
2
Finnish Red Cross Blood Service, Helsinki, Finland.
3
Centre for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, The Netherlands.

Abstract

Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. We recently found IgG Fc-glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core-fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). Besides a significant decrease in Fc-fucosylation after the first pregnancy (P = 0·0124), Fc-glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT.

KEYWORDS:

Fc-fucosylation; Fc-glycosylation; Fetal or neonatal alloimmune thrombocytopenia; alloantibodies; immunology

PMID:
27017954
DOI:
10.1111/bjh.14053
[Indexed for MEDLINE]

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