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

Journal article
Authors J. S. Westman
John Benktander
J. R. Storry
T. Peyrard
A. K. Hult
A. Hellberg
Susann Teneberg
M. L. Olsson
Published in Journal of Biological Chemistry
Volume 290
Issue 30
Pages 18505-18518
ISSN 0021-9258
Publication year 2015
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 18505-18518
Language en
Links dx.doi.org/10.1074/jbc.M115.655308
Keywords UDP-N-ACETYLGALACTOSAMINE, MASS-SPECTROMETRY, INTERNATIONAL-SOCIETY, EXPRESSION CLONING, P PHENOTYPE, SYNTHASE, GLYCOSYLTRANSFERASES, GLYCOLIPIDS, ANTIBODIES, GLYCOPROTEINS, Biochemistry & Molecular Biology, NIGUCHI N, 1984, JOURNAL OF BIOLOGICAL CHEMISTRY, V259, P5637, LCH J, 1957, JOURNAL OF BIOLOGICAL CHEMISTRY, V226, P497
Subject categories Biochemistry and Molecular Biology

Abstract

The x(2) 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-beta-N-acetylgalactosaminyl-transferase encoded by B3GALNT1. It is the most abundant non-acid glycosphingolipid on erythrocytes and displays the same terminal disaccharide, GalNAc beta 3Gal, as x(2). We encountered a patient with mutations in B3GALNT1 causing the rare P-deficient P-1(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 x(2) and sialylated forms of x(2), whereas x(2) is lacking on P-deficient erythrocytes. Overexpression of B3GALNT1 resulted in synthesis of both P and x(2). Knockdown experiments with siRNA against B3GALNT1 diminished x(2) levels. We conclude that x(2) fulfills blood group criteria and is synthesized by UDP-N-acetylgalactosamine: globotriaosylceramide 3-beta-N-acetylgalactosaminyltransferase. Based on this linkage, we proposed that x(2) 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 P-1(k) or P-2(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.

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