Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia
Myrthe E. Sonneveld
Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorSuvi Natunen
Finnish Red Cross Blood Service, Helsinki, Finland
Search for more papers by this authorSusanna Sainio
Finnish Red Cross Blood Service, Helsinki, Finland
Search for more papers by this authorCarolien A. M. Koeleman
Centre for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, The Netherlands
Search for more papers by this authorStephanie Holst
Centre for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, The Netherlands
Search for more papers by this authorGillian Dekkers
Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorJoke Koelewijn
Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorJukka Partanen
Finnish Red Cross Blood Service, Helsinki, Finland
Search for more papers by this authorC. Ellen van der Schoot
Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorManfred Wuhrer
Centre for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, The Netherlands
Search for more papers by this authorCorresponding Author
Gestur Vidarsson
Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Correspondence: Dr. Gestur Vidarsson, Department of Experimental Immunohaematology, Sanquin Research, and Landsteiner Laboratory, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands.
E-mail: [email protected]
Search for more papers by this authorMyrthe E. Sonneveld
Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorSuvi Natunen
Finnish Red Cross Blood Service, Helsinki, Finland
Search for more papers by this authorSusanna Sainio
Finnish Red Cross Blood Service, Helsinki, Finland
Search for more papers by this authorCarolien A. M. Koeleman
Centre for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, The Netherlands
Search for more papers by this authorStephanie Holst
Centre for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, The Netherlands
Search for more papers by this authorGillian Dekkers
Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorJoke Koelewijn
Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorJukka Partanen
Finnish Red Cross Blood Service, Helsinki, Finland
Search for more papers by this authorC. Ellen van der Schoot
Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorManfred Wuhrer
Centre for Proteomics and Metabolomics, Leiden University Medical Centre, Leiden, The Netherlands
Search for more papers by this authorCorresponding Author
Gestur Vidarsson
Department of Experimental Immunohaematology, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Correspondence: Dr. Gestur Vidarsson, Department of Experimental Immunohaematology, Sanquin Research, and Landsteiner Laboratory, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands.
E-mail: [email protected]
Search for more papers by this authorAbstract
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.
Supporting Information
| Filename | Description |
|---|---|
| bjh14053-sup-0001-SupInfo.pdfPDF document, 267.9 KB | Fig S1. Total galactosylation and sialylation decreases significant after delivery while anti-HPA-1a glycosylation remains constant. Fig S2. Anti-HPA-1a antibody level and platelet count do not show a strict correlation. Fig S3. Score plots of the principle component analysis (PCA) show anti-HPA-1a fucosylation and sialylation to be the most important variables. Fig S4. Principle component analysis (PCA) suggests fucosylation as strongest predictor for severity in individuals at risk. Table SI. Cohort description. Table SII. Measured and observed clinical parameters in each pregnancy. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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