A KEL gene encoding serine at position 193 of the Kell glycoprotein results in expression of KEL1 antigen

Authors

  • Joyce Poole,

    1. From the Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK; BST SRC Bern AG, Bern, Switzerland; the Department of Hematology and Central Hematology Laboratory, Division of Transfusion Medicine, Inselspital, University, Bern, Switzerland; and DiaMed AG, Cressier, Switzerland.
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  • Nicole Warke,

    1. From the Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK; BST SRC Bern AG, Bern, Switzerland; the Department of Hematology and Central Hematology Laboratory, Division of Transfusion Medicine, Inselspital, University, Bern, Switzerland; and DiaMed AG, Cressier, Switzerland.
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  • Hein Hustinx,

    1. From the Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK; BST SRC Bern AG, Bern, Switzerland; the Department of Hematology and Central Hematology Laboratory, Division of Transfusion Medicine, Inselspital, University, Bern, Switzerland; and DiaMed AG, Cressier, Switzerland.
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  • Behrouz Mansouri Taleghani,

    1. From the Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK; BST SRC Bern AG, Bern, Switzerland; the Department of Hematology and Central Hematology Laboratory, Division of Transfusion Medicine, Inselspital, University, Bern, Switzerland; and DiaMed AG, Cressier, Switzerland.
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  • Peter Martin,

    1. From the Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK; BST SRC Bern AG, Bern, Switzerland; the Department of Hematology and Central Hematology Laboratory, Division of Transfusion Medicine, Inselspital, University, Bern, Switzerland; and DiaMed AG, Cressier, Switzerland.
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  • Kirstin Finning,

    1. From the Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK; BST SRC Bern AG, Bern, Switzerland; the Department of Hematology and Central Hematology Laboratory, Division of Transfusion Medicine, Inselspital, University, Bern, Switzerland; and DiaMed AG, Cressier, Switzerland.
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  • Vanja Karamatic Crew,

    1. From the Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK; BST SRC Bern AG, Bern, Switzerland; the Department of Hematology and Central Hematology Laboratory, Division of Transfusion Medicine, Inselspital, University, Bern, Switzerland; and DiaMed AG, Cressier, Switzerland.
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  • Carole Green,

    1. From the Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK; BST SRC Bern AG, Bern, Switzerland; the Department of Hematology and Central Hematology Laboratory, Division of Transfusion Medicine, Inselspital, University, Bern, Switzerland; and DiaMed AG, Cressier, Switzerland.
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  • Imelda Bromilow,

    1. From the Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK; BST SRC Bern AG, Bern, Switzerland; the Department of Hematology and Central Hematology Laboratory, Division of Transfusion Medicine, Inselspital, University, Bern, Switzerland; and DiaMed AG, Cressier, Switzerland.
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  • Geoff Daniels

    1. From the Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK; BST SRC Bern AG, Bern, Switzerland; the Department of Hematology and Central Hematology Laboratory, Division of Transfusion Medicine, Inselspital, University, Bern, Switzerland; and DiaMed AG, Cressier, Switzerland.
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  • VKC is funded by a grant from DiaMed AG.

Geoff Daniels, Bristol Institute for Transfusion Sciences, National Blood Service, Southmead Road, Bristol BS10 5ND, UK; e-mail: geoff.daniels@nbs.nhs.uk.

Abstract

BACKGROUND: The KEL2/KEL1 (k/K) blood group polymorphism represents 578C>T in the KEL gene and Thr193Met in the Kell glycoprotein. Anti-KEL1 can cause severe hemolytic disease of the fetus and newborn. Molecular genotyping for KEL*1 is routinely used for assessing whether a fetus is at risk. Red blood cells (RBCs) from a KEL:1 blood donor (D1) were found to have abnormal KEL1 expression during evaluation of anti-KEL1 reagents.

STUDY DESIGN AND METHODS: Kell genotyping methods, including KEL exon 6 direct sequencing, were applied. KEL cDNA from D1 was sequenced. Flow cytometry was used to assess KEL1 and KEL2 RBC expression.

RESULTS: RBCs from the donor, her mother, and an unrelated donor gave weak or negative reactions with some anti-KEL1 reagents. Other Kell-system antigens appeared normal. The three individuals were homozygous for KEL C578 (KEL*2) but heterozygous for a 577A>T transversion, encoding Ser193. They appeared to be KEL*2 homozygotes by routine genotyping methods. Flow cytometry revealed weak KEL1 expression and normal KEL2, similar to that of KEL*2 homozygotes.

CONCLUSION: Ser193 in the Kell glycoprotein appears to result in expression of abnormal KEL1, in addition to KEL2. The mutation is not detected by routine Kell genotyping methods and, because of unpredicted KEL1 expression, could lead to a misdiagnosis.

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