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J Biol Chem. 2015 Jul 24;290(30):18505-18. doi: 10.1074/jbc.M115.655308. Epub 2015 Jun 8.

Identification of the Molecular and Genetic Basis of PX2, a Glycosphingolipid Blood Group Antigen Lacking on Globoside-deficient Erythrocytes.

Author information

1
From the Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, SE-22184 Lund, Sweden.
2
the Institute of Biomedicine, The Sahlgrenska Academy, Gothenburg University, SE-40530 Gothenburg, Sweden.
3
From the Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, SE-22184 Lund, Sweden, the Clinical Immunology and Transfusion Medicine, Laboratory Medicine, Office of Medical Services, Region Skåne, SE-22185 Lund, Sweden.
4
the Institut National de la Transfusion Sanguine (INTS), Département Centre National de Référence pour les Groupes Sanguins, F-75015 Paris, France, and the Laboratory of Excellence GR-Ex, F-75015 Paris, France.
5
the Institute of Biomedicine, The Sahlgrenska Academy, Gothenburg University, SE-40530 Gothenburg, Sweden, Susann.Teneberg@medkem.gu.se.
6
From the Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, SE-22184 Lund, Sweden, the Clinical Immunology and Transfusion Medicine, Laboratory Medicine, Office of Medical Services, Region Skåne, SE-22185 Lund, Sweden, Martin_L.Olsson@med.lu.se.

Abstract

The x2 glycosphingolipid is expressed on erythrocytes from individuals of all common blood group phenotypes and elevated on cells of the rare P/P1/P(k)-negative p blood group phenotype. Globoside or P antigen is synthesized by UDP-N-acetylgalactosamine:globotriaosyl-ceramide 3-β-N-acetylgalactosaminyltransferase encoded by B3GALNT1. It is the most abundant non-acid glycosphingolipid on erythrocytes and displays the same terminal disaccharide, GalNAcβ3Gal, as x2. We encountered a patient with mutations in B3GALNT1 causing the rare P-deficient P1 (k) phenotype and whose pretransfusion plasma was unexpectedly incompatible with p erythrocytes. The same phenomenon was also noted in seven other unrelated P-deficient individuals. Thin-layer chromatography, mass spectrometry, and flow cytometry were used to show that the naturally occurring antibodies made by p individuals recognize x2 and sialylated forms of x2, whereas x2 is lacking on P-deficient erythrocytes. Overexpression of B3GALNT1 resulted in synthesis of both P and x2. Knockdown experiments with siRNA against B3GALNT1 diminished x2 levels. We conclude that x2 fulfills blood group criteria and is synthesized by UDP-N-acetylgalactosamine: globotriaosylceramide 3-β-N-acetylgalactosaminyltransferase. Based on this linkage, we proposed that x2 joins P in the GLOB blood group system (ISBT 028) and is renamed PX2 (GLOB2). Thus, in the absence of a functional P synthase, neither P nor PX2 are formed. As a consequence, naturally occurring anti-P and anti-PX2 can be made. Until the clinical significance of anti-PX2 is known, we also recommend that rare P1 (k) or P2 (k) erythrocyte units are preferentially selected for transfusion to P(k) patients because p erythrocytes may pose a risk for hemolytic transfusion reactions due to their elevated PX2 levels.

KEYWORDS:

blood; blood group; erythrocyte; glycolipid; glycolipid structure; glycosphingolipid; glycosyltransferase; transfusion medicine

PMID:
26055721
PMCID:
PMC4513111
DOI:
10.1074/jbc.M115.655308
[Indexed for MEDLINE]
Free PMC Article

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