Molecular basis of two novel and related high-prevalence antigens in the Kell blood group system, KUCI and KANT, and their serologic and spatial association with K11 and KETI

Authors

  • Randall W. Velliquette,

    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
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  • Kim Hue-Roye,

    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
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  • Christine Lomas-Francis,

    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
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  • Barbara Gillen,

    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
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  • Jennifer Schierts,

    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
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  • Kristie Gentzkow,

    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
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  • Thierry Peyrard,

    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
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  • Inge von Zabern,

    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
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  • Willy A. Flegel,

    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
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  • Karen Rodberg,

    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
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  • Asim K. Debnath,

    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
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  • Soohee Lee,

    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
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  • Marion E. Reid

    Corresponding author
    1. Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York
    2. Laboratory of Immunochemistry, New York Blood Center, New York, New York
    3. Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York
    4. Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York
    5. Memorial Blood Centers, St Paul, Minnesota
    6. Medcenter One, Bismarck, North Dakota
    7. National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France
    8. Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany
    9. Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland
    10. American Red Cross, Southern California Region, Pomona, California
    • Address reprint requests to: Marion E. Reid, PhD, Laboratory of Immunochemistry, New York Blood Center, 310 East 67 Street, New York, NY 10065; e-mail: mreid@nybloodcenter.org.

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  • Statement of disclaimer for WF: The views expressed do not necessarily represent the view of the National Institutes of Health, the Department of Health and Human Services, or the U.S. Federal Government.
  • This study was funded in part by NIH grant R01 HL075716 (SL).

Abstract

Background

The numerous antigens in the Kell blood group system result from missense nucleotide changes in KEL. Antibodies to antigens in this system can be clinically important. We describe six probands whose plasma contained antibodies to high-prevalence Kell antigens and discuss their relationship.

Study Design and Methods

Polymerase chain reaction amplification, direct sequencing, restriction fragment length polymorphism assays, hemagglutination, flow cytometry, and protein modeling were performed by standard methods.

Results

Proband 1 (KUCI) and her serologically compatible sister were heterozygous for a nucleotide change in Exon 11 (KEL*1271C/T; Ala424Val). Proband 2 (KANT) was heterozygous for KEL*1283G/T (Arg428Leu) and KEL*1216C/T (Arg406Stop) in Exon 11. Red blood cells (RBCs) from Proband 1 and her sister were not agglutinated by plasma from Proband 2; however, RBCs from Proband 2 were agglutinated by plasma from Proband 1. Probands 3, 4, 5, and 6 had the KEL*1391C>T change associated with the previously reported KETI– phenotype. Proband 5 was also homozygous for KEL*905T>C encoding the K11–K17+ phenotype. Hemagglutination studies revealed an association between KUCI, KANT, KETI, and K11. Protein modeling indicated that whereas Ala424 and Arg428 are clustered, Val302 and Thr464 are not.

Conclusion

Ala424 in the Kell glycoprotein is associated with the high-prevalence Kell antigen, KUCI (ISBT 006032), which is detected by the antibody of Proband 1. Arg428 is associated with the high-prevalence Kell antigen, KANT (ISBT 006033). The association between KUCI, KANT, KETI, and K11 and the results of protein modeling are discussed.

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