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D category IV: a group of clinically relevant and phylogenetically diverse partial D

Authors

  • Inge von Zabern,

    1. Department of Transfusion Medicine, University Hospital, Ulm, Germany
    2. Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany
    3. DRK (German Red Cross) Blood Donor Service Baden-Württemberg–Hessen, Institute, Ulm, Germany
    4. DRK Blood Donor Service NSTOB, Institute, Springe, Germany
    5. Scientific Support Services, LifeShare Blood Centers, Shreveport, Louisiana
    6. Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
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  • Franz F. Wagner,

    1. Department of Transfusion Medicine, University Hospital, Ulm, Germany
    2. Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany
    3. DRK (German Red Cross) Blood Donor Service Baden-Württemberg–Hessen, Institute, Ulm, Germany
    4. DRK Blood Donor Service NSTOB, Institute, Springe, Germany
    5. Scientific Support Services, LifeShare Blood Centers, Shreveport, Louisiana
    6. Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
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  • Joann M. Moulds,

    1. Department of Transfusion Medicine, University Hospital, Ulm, Germany
    2. Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany
    3. DRK (German Red Cross) Blood Donor Service Baden-Württemberg–Hessen, Institute, Ulm, Germany
    4. DRK Blood Donor Service NSTOB, Institute, Springe, Germany
    5. Scientific Support Services, LifeShare Blood Centers, Shreveport, Louisiana
    6. Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
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  • John J. Moulds,

    1. Department of Transfusion Medicine, University Hospital, Ulm, Germany
    2. Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany
    3. DRK (German Red Cross) Blood Donor Service Baden-Württemberg–Hessen, Institute, Ulm, Germany
    4. DRK Blood Donor Service NSTOB, Institute, Springe, Germany
    5. Scientific Support Services, LifeShare Blood Centers, Shreveport, Louisiana
    6. Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
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  • Willy A. Flegel

    Corresponding author
    1. Department of Transfusion Medicine, University Hospital, Ulm, Germany
    2. Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany
    3. DRK (German Red Cross) Blood Donor Service Baden-Württemberg–Hessen, Institute, Ulm, Germany
    4. DRK Blood Donor Service NSTOB, Institute, Springe, Germany
    5. Scientific Support Services, LifeShare Blood Centers, Shreveport, Louisiana
    6. Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    • Address reprint requests to: Willy A. Flegel, MD, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Building 10, Room 1C733c, 10 Center Drive, Bethesda, MD 20892-1184; e-mail: bill.flegel@nih.gov.

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  • The views expressed do not necessarily represent the view of the National Institutes of Health, the Department of Health and Human Services, or the US Federal Government.
  • This work was supported by the Intramural Research Programs of the DRK-Blutspendedienst Baden-Württemberg–Hessen, Mannheim, and the NIH Clinical Center.

Abstract

Background

The D typing strategies in several European countries protect carriers of D category VI (DVI) from anti-D immunization but not carriers of other partial D. Besides DVI, one of the clinically most important partial D is D category IV (DIV). A detailed description and direct comparison of the different DIV types was missing.

Study Design and Methods

RHD nucleotide sequences were determined from genomic DNA. D epitope patterns were established with commercial monoclonal anti-D panels.

Results

DIV comprises several variants of the D antigen with distinct serology, molecular structures, evolutionary origins, and ethnic prevalences. The DIV phenotype is determined by 350H shared by all, but not limited to, DIV variants which are further divided into DIVa and DIVb. The DIVa phenotype is expressed by DIV Type 1.0 harboring 350H and the dispersed amino acids 62F, 137V, and 152T. The DIVb phenotype is expressed by DIV Type 3 to Type 5 representing RHD-CE-D hybrids. Four of the six postulated DIV variants were encountered among 23 DIV samples analyzed. Of 12 DIV carriers with anti-D, 10 were female and seven likely immunized by pregnancy. Two DIV-related alleles are newly described: DWN, which differs from DIV Type 4 by 350D and epitope pattern. DNT carries 152T, known to cause a large D antigen density.

Conclusion

DIV alleles arose from at least two independent evolutionary events. DIV Type 1.0 with DIVa phenotype belongs to the oldest extant human RHD alleles. DIV Type 2 to Type 5 with DIVb phenotype arose from more recent gene conversions. Anti-D immunization, especially dreaded in pregnancies, will be avoided not only in carriers of DVI but also in carriers of other D variants like DIV, if our proposed D typing strategy is adopted.

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