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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 LU ; Benktander, John; Storry, Jill LU ; Peyrard, Thierry; Hult, Annika LU ; Hellberg, Åsa LU ; Teneberg, Susann and Olsson, Martin L LU (2015) In Journal of Biological Chemistry 290(30). p.18505-18518
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:globotriaosylceramide 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 pre-transfusion plasma was unexpectedly incompatible with p erythrocytes. The same phenomenon was also noted in seven other unrelated P-deficient individuals. Thin-layer... (More)
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:globotriaosylceramide 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 pre-transfusion 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 was used to show that the naturally-occurring antibodies made by p individuals recognise x2 and sialylated forms of x2, while 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 β1,3GalNAc-T1. 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) RBC units are preferentially selected for transfusion to P(k) patients since p RBCs may pose a risk for hemolytic transfusion reactions due to their elevated PX2 levels. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
290
issue
30
pages
18505 - 18518
publisher
ASBMB
external identifiers
  • pmid:26055721
  • wos:000358512100023
  • scopus:84937798145
ISSN
1083-351X
DOI
10.1074/jbc.M115.655308
language
English
LU publication?
yes
id
e9f97421-0973-4e95-adf6-0d12d0eb795e (old id 7487431)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26055721?dopt=Abstract
date added to LUP
2015-07-07 17:22:30
date last changed
2017-10-09 09:35:18
@article{e9f97421-0973-4e95-adf6-0d12d0eb795e,
  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:globotriaosylceramide 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 pre-transfusion 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 was used to show that the naturally-occurring antibodies made by p individuals recognise x2 and sialylated forms of x2, while 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 β1,3GalNAc-T1. 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) RBC units are preferentially selected for transfusion to P(k) patients since p RBCs may pose a risk for hemolytic transfusion reactions due to their elevated PX2 levels.},
  author       = {Westman, Julia and Benktander, John and Storry, Jill and Peyrard, Thierry and Hult, Annika and Hellberg, Åsa and Teneberg, Susann and Olsson, Martin L},
  issn         = {1083-351X},
  language     = {eng},
  number       = {30},
  pages        = {18505--18518},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Identification of the molecular and genetic basis of PX2, a glycosphingolipid blood group antigen lacking on globoside-deficient erythrocytes.},
  url          = {http://dx.doi.org/10.1074/jbc.M115.655308},
  volume       = {290},
  year         = {2015},
}