Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia
| Autor: | Myrthe E. Sonneveld, Susanna Sainio, J. M. Koelewijn, C. Ellen van der Schoot, Jukka Partanen, Manfred Wuhrer, Suvi Natunen, Gestur Vidarsson, Carolien A. M. Koeleman, Stephanie Holst, Gillian Dekkers |
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| Přispěvatelé: | Other departments, Landsteiner Laboratory, Clinical Haematology |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Blood Platelets Glycosylation Hemorrhage Severity of Illness Index Mass Spectrometry immunology 03 medical and health sciences 0302 clinical medicine Antigen Isoantibodies Predictive Value of Tests Pregnancy Medicine Humans Platelet Antigens Human Platelet Fetal or neonatal alloimmune thrombocytopenia Fc-glycosylation Fucosylation Fucose Fc-fucosylation Fetus biology business.industry Integrin beta3 Galactose Hematology medicine.disease alloantibodies Human platelet antigen N-Acetylneuraminic Acid 3. Good health Antibodies Anti-Idiotypic Thrombocytopenia Neonatal Alloimmune 030104 developmental biology Immunoglobulin G Immunology Neonatal alloimmune thrombocytopenia biology.protein Female Antibody business 030215 immunology |
| Zdroj: | British journal of haematology, 174(2), 310-320. Wiley-Blackwell British Journal of Haematology, 174(2), 310-320. WILEY-BLACKWELL |
| ISSN: | 0007-1048 |
| Popis: | Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal antiplatelet 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 Fc gamma RIIIa and Fc gamma RIIIb, 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. |
| Databáze: | OpenAIRE |
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