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

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-?-N-acetylgalactosaminyltransferase encoded by B3GALNT1. It is the most abundant non-acid glycosphingolipid on erythrocytes and displays the same terminal disaccharide, GalNAc?3Gal, 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-?-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.

SUBMITTER: Westman JS

PROVIDER: S-EPMC4513111 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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

Westman Julia S JS Benktander John J Storry Jill R JR Peyrard Thierry T Hult Annika K AK Hellberg Åsa Å Teneberg Susann S Olsson Martin L ML

The Journal of biological chemistry 20150608 30

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 mut ...[more]

PMID: 26055721

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Project description:A monoclonal antibody, MRG-1, was produced by immunizing a mouse with a human ovarian mucinous cyst adenocarcinoma-derived cell line, RMUG-L. By immunohistochemical staining, the antigen was found to be exclusively localized in the intracellular structures of the cells used as the antigen and of the epithelial cells in normal human cervical glands. However, although the antigen was predominantly detected in the plasma membrane and the intercellular structure of the middle layer of normal human cervical squamous epithelium (92%), it was also contained in the intracellular structure of cervical epidermal carcinoma at a high frequency (80%). The striking difference in the distribution of the MRG-1 antigen between normal and cancerous tissues was found to be a cervical carcinoma-associated phenomenon and a useful tumor marker for immunohistochemical examination. Since the antigen was found to be of a blood group A-related nature by immunohistochemical staining of the tissues and to be a glycosphingolipid, it was purified from human erythrocytes of blood group A, and the structure was concluded to be GalNAc alpha 1-3Gal(2-1 alpha Fuc)beta 1-3GalNAc alpha 1-3Gal(2-1 alpha Fuc)-beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1' Cer, blood group A type 3 chain-containing glycosphingolipid, by NMR, negative ion FABMS and permethylation analysis. In the subcellular localization analysis of the antigen, type 3-A glycosphingolipid antigen was detected in the Golgi body and the microsomes of RMUG-L cells, and the distribution coincided with the finding by immunohistochemical staining. In addition, in cervical epidermal carcinoma, although the blood group A, mainly type 2-A chain, was localized in the plasma membrane and the intercellular structure, the blood group A type 3 chain was selectively found in the perinuclear structure. Also, the blood group A type 3 chain in cervical dysplasia as well as that in normal cervix was predominant in the plasma membrane. Thus, the selective intracellular localization of blood group A type 3 chain was a phenomenon characteristic of cervical epidermal carcinoma and the carcinoma in situ.

Dataset Information

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

Publications

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

Similar Datasets

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