<abstract xmlns="http://www.w3.org/1999/xhtml">

The high-prevalence blood group antigen, Sda, had been puzzling blood bankers and transfusionists for at least a decade when it was reported in 1967. The characteristic mix of agglutinates and free red blood cells (RBCs), caused by anti-Sda, is seen with the RBCs from 90 percent of individuals of European descent. However, only 2–4 percent of individuals are truly Sd(a−) and may produce anti-Sda. The antibodies, generally considered insignificant, may cause hemolytic transfusion reactions with high-expressing Sd(a+) RBCs (e.g., the unusual Cad phenotype, which can also be polyagglutinable). The Sda glycan, GalNAcβ1-4(NeuAcα2-3)Gal-R, is produced in the gastrointestinal and urinary systems, while its origin on RBCs is more controversial. According to current theory, Sda is likely to be passively adsorbed in low amounts, except in Cad individuals, where it has been found on erythroid proteins and at higher levels. The long-standing hypothesis that <italic>B4GALNT2</italic> encodes the Sda synthase was confirmed in 2019, since homozygosity for a variant allele with rs7224888:C produces a non-functional enzyme associated with most cases of the Sd(a−) phenotype. Thereby, the SID blood group system was acknowledged as number 038 by the International Society of Blood Transfusion. Although the genetic background of Sd(a−) was settled, questions remain. The genetic background of the Cad phenotype has not yet been determined, and the source of the RBC-carried Sda is unknown. Furthermore, the interest of Sda stretches beyond transfusion medicine. Some tantalizing examples are lowered antigen levels in malignant tissue compared with normal tissue and interference with infectious agents like <italic>Escherichia coli</italic>, influenza virus, and malaria parasites.
</abstract>

The high-prevalence blood group antigen, Sda, had been puzzling blood bankers and transfusionists for at least a decade when it was reported in 1967. The characteristic mix of agglutinates and free red blood cells (RBCs), caused by anti-Sda, is seen with the RBCs from 90 percent of individuals of European descent. However, only 2–4 percent of individuals are truly Sd(a−) and may produce anti-Sda. The antibodies, generally considered insignificant, may cause hemolytic transfusion reactions with high-expressing Sd(a+) RBCs (e.g., the unusual Cad phenotype, which can also be polyagglutinable). The Sda glycan, GalNAcβ1-4(NeuAcα2-3)Gal-R, is produced in the gastrointestinal and urinary systems, while its origin on RBCs is more controversial. According to current theory, Sda is likely to be passively adsorbed in low amounts, except in Cad individuals, where it has been found on erythroid proteins and at higher levels. The long-standing hypothesis that B4GALNT2 encodes the Sda synthase was confirmed in 2019, since homozygosity for a variant allele with rs7224888:C produces a non-functional enzyme associated with most cases of the Sd(a−) phenotype. Thereby, the SID blood group system was acknowledged as number 038 by the International Society of Blood Transfusion. Although the genetic background of Sd(a−) was settled, questions remain. The genetic background of the Cad phenotype has not yet been determined, and the source of the RBC-carried Sda is unknown. Furthermore, the interest of Sda stretches beyond transfusion medicine. Some tantalizing examples are lowered antigen levels in malignant tissue compared with normal tissue and interference with infectious agents like Escherichia coli, influenza virus, and malaria parasites.

SID: a new carbohydrate blood group system based on a well-characterized but still mysterious antigen of great pathophysiologic interest

Immunohematology

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

The high-prevalence blood group antigen, Sda, had been puzzling blood bankers and transfusionists for at least a decade when it was reported in 1967. The...

RBC phenotype	Prevalence (%)	Population	Size of study/ies
Sd(a−)	9 (2–4 in other tissue)	British	290 and 144
Sd(a+)	91	British
Cad	0–0.07	French	250,000* and 78,526*
	0.03	Japanese	51,429* and 3183^†
	0.14	Canadian	1425*
	0.26	Thai	14,261*

Phenotype	Allele name	Nucleotide change^†	rs number	Exon/intron	Resulting amino acid change^†	Accession number
SID:1 or Sd(a+)	SID*01	…	…	…	…	AJ517770
Sd(a−)	SID*01N.01^‡	c.1396T>C	rs7224888	E10	p.Cys466Arg	MK765047
Sd(a−)	SID*01N.02	c.1134+5G>A	rs72835417	i8	Splice-site defect predicted	MK797056
Sd(a−)	SID*01N.03	c.1307A>G	rs148441237	E10	p.Glu436Arg	MK765048
Sd(a−)	SID*01N.04	c.1567C>T	rs61743617	E11	p.Arg523Trp	MK765049

SID: a new carbohydrate blood group system based on a well-characterized but still mysterious antigen of great pathophysiologic interest

Article Category: Blood Group Review

Online veröffentlicht: 05. Apr. 2023

Seitenbereich: 1 - 10

DOI: https://doi.org/10.21307/immunohematology-2023-002

© 2023 L. Stenfelt et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig. 1

Prevalence of the RBC phenotypes in specified populations

Summary of the current knowledge on the genetic basis of null phenotypes in the SID blood group system (International Society of Blood Transfusion system number 038)6