The implementation of surface plasmon resonance technique in monitoring pregnancies with expected fetal and neonatal alloimmune thrombocytopenia

Authors

  • Tamam Bakchoul,

    Corresponding author
    1. Institute for Immunology und Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany
    2. the Platelet Immunology Unit and the Immunology Transfusion Unit, INTS, Paris, France
    3. Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service, Dessau, Germany
    • Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Giessen, Germany
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  • Gérald Bertrand,

    1. Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Giessen, Germany
    2. Institute for Immunology und Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany
    3. the Platelet Immunology Unit and the Immunology Transfusion Unit, INTS, Paris, France
    4. Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service, Dessau, Germany
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  • Annika Krautwurst,

    1. Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Giessen, Germany
    2. Institute for Immunology und Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany
    3. the Platelet Immunology Unit and the Immunology Transfusion Unit, INTS, Paris, France
    4. Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service, Dessau, Germany
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  • Hartmut Kroll,

    1. Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Giessen, Germany
    2. Institute for Immunology und Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany
    3. the Platelet Immunology Unit and the Immunology Transfusion Unit, INTS, Paris, France
    4. Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service, Dessau, Germany
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  • Gregor Bein,

    1. Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Giessen, Germany
    2. Institute for Immunology und Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany
    3. the Platelet Immunology Unit and the Immunology Transfusion Unit, INTS, Paris, France
    4. Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service, Dessau, Germany
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  • Ulrich J. Sachs,

    1. Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Giessen, Germany
    2. Institute for Immunology und Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany
    3. the Platelet Immunology Unit and the Immunology Transfusion Unit, INTS, Paris, France
    4. Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service, Dessau, Germany
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  • Sentot Santoso,

    1. Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Giessen, Germany
    2. Institute for Immunology und Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany
    3. the Platelet Immunology Unit and the Immunology Transfusion Unit, INTS, Paris, France
    4. Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service, Dessau, Germany
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    • Both laboratories contributed equally to the study.
  • Cécile Kaplan

    1. Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Giessen, Germany
    2. Institute for Immunology und Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany
    3. the Platelet Immunology Unit and the Immunology Transfusion Unit, INTS, Paris, France
    4. Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service, Dessau, Germany
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    • Both laboratories contributed equally to the study.

  • This work was supported by a grant for TB from the University Hospital Giessen and Marburg GmbH.

Address reprint requests to: Tamam Bakchoul, Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University Greifswald, Sauerbruchstrasse, 17475 Greifswald, Germany; e-mail: bakchoult@uni-greifswald.de.

Abstract

Background

Maternal anti-HPA-1a alloantibodies are responsible for most cases of severe fetal and neonatal alloimmune thrombocytopenia (FNAIT). The presence of HPA-1a alloantibodies in maternal blood alone does not predict the fetal platelet (PLT) count, and the predictivity of antibody titers determined by enzyme immunoassays (EIAs) is debated. In contrast to EIA, surface plasmon resonance (SPR) provides information on antibody-binding properties.

Study Design and Methods

Sequential sera from pregnant women with expected FNAIT were assessed for HPA-1a alloantibodies using SPR. Group I (n = 6) was treated with intravenous immunoglobulin (IVIG) and steroids beginning at 19 weeks of gestation (w.g.), and Group II (n = 4) received intrauterine PLT transfusions (IUT) beginning at 22 w.g. Maternal alloantibodies were quantified using an HPA-1a monoclonal antibody (MoAb) as a standard. Antibody avidity was determined as the ratio of B700 (end of the dissociation phase) to B350 (end of the association phase); the area under the curve (AUC) was calculated to determine overall antibody binding.

Results

After 22 w.g., alloantibody characteristics remained stable in both groups, while there was a steep decrease in B700 and B350 values between 16 and 22 w.g. (assessed only in Group I), indicating a decrease in anti-HPA-1a alloantibody concentrations. Interestingly, the AUCs of the last maternal sample before elective delivery appeared to be correlated with fetal and neonatal PLT counts (p = 0.014 and 0.017, respectively).

Conclusion

SPR provides quantitative information on HPA-1a alloantibody characteristics in addition to monoclonal antibody–specific immobilization of platelet antigens. SPR results can be calibrated using a MoAb standard and should be further assessed for a potential correlation with fetal PLT count.

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