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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7487431
- author
- Westman, Julia
LU
; Benktander, John
; Storry, Jill
LU
; Peyrard, Thierry
; Hult, Annika
LU
; Hellberg, Åsa
LU
; Teneberg, Susann
and Olsson, Martin L
LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 290
- issue
- 30
- pages
- 18505 - 18518
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:26055721
- wos:000358512100023
- scopus:84937798145
- pmid:26055721
- 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
- 2016-04-01 10:02:46
- date last changed
- 2022-03-04 07:38:29
@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 = {{American Society for Biochemistry and Molecular Biology}},
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}},
doi = {{10.1074/jbc.M115.655308}},
volume = {{290}},
year = {{2015}},
}