SCAR: The high‐prevalence antigen 013.008 in the Scianna blood group system

Abstract

Background: The Scianna (SC) blood group system comprises seven antigens. They reside on the erythroblast membrane-associated glycoprotein (ERMAP). The ERMAP and RHCE genes are juxtaposed to each other on chromosome 1. We report a novel SC antigen. Study Design and Methods: Blood samples came from a patient and his two sisters in Saudi Arabia. To investigate the antibody specificity we used the column agglutination technique and soluble recombinant ERMAP protein. The significance of anti-SCAR was evaluated by the transfusion history and a monocyte monolayer assay. We determined the genomic sequence of ERMAP and RHCE genes. Results: The patientʼs serum showed an antibody of titer 8 against a highprevalence antigen. The soluble recombinant ERMAP protein inhibited the antibody. The propositus genotyped homozygous for an ERMAP:c.424C>G variant, for which his sisters were heterozygous. The c.424C>G variant occurred in the SC*01 allele in one haplotype with the RHCE*03 (RHCE*cE) allele. No signs of hemolysis occurred following an incompatible blood transfusion. The monocyte monolayer assay was negative. Conclusions: We characterized a high-prevalence antigen, with the proposed name "SCAR," which is the eighth antigen of the Scianna blood group system (proposed designation 013.008). Individuals homozygous for ERMAP:p. (Gln142Glu) protein variant can produce anti-SCAR. Although we did not observe any sign of hemolysis at this time, the anti-SCAR prompted a change of the treatment regimen. A review of the known reports indicated that all SC alloantibodies of sufficient titer should be considered capable of causing hemolysis.

When recombinant proteins can replace rare red cells in immunohematology workups

“…70 The ERMAP protein inhibited the antibody in our study, which allowed us to define the antibody as being directed against a hitherto unknown high-prevalence Scianna antigen, dubbed SCAR (SC8). 70 The standard approach was using red cells with rare null phenotypes (null cells) [102][103][104] to define new blood group systems and new high-prevalence antigens. Unless alternatives are available, null cells are needed because ISBT guidelines 1 for establishment of new blood group systems or new antigens in an established system require demonstration of antigen expression specifically in erythroid cells.…”

“…The ISBT Working Party on Red Cell Immunogenetics and Blood Group Terminology has begun accepting evidence from rBGPs alone, 65,66,70,81,84 without testing against red cells lacking the protein or antigen, to satisfy the requirements 1 for defining novel blood group antigens. The first example was the YTEG antigen of the YT blood group system in 2017, 65 followed by the YT antigens YTLI and YTOT 66 and the Indian antigen INSL 84 in 2018.…”

“…Since 1996, multiple studies have exploited soluble or cell membrane‐bound recombinant proteins to screen human sera for blood‐group‐specific antibodies (Table 1). 27,29,32,44–95 There are 190 red cell antigens classified as high‐prevalence by the ISBT (see web resources) 96 . To identify antibody specificities against all high‐prevalence antigens, up to 190 distinct red cells lacking high‐prevalence antigens or lacking the whole carrier protein would be needed.…”

“…To confirm a new high‐prevalence antigen actually belonged to the Scianna blood group system, we recently applied a soluble recombinant ERMAP protein 70 . The ERMAP protein inhibited the antibody in our study, which allowed us to define the antibody as being directed against a hitherto unknown high‐prevalence Scianna antigen, dubbed SCAR (SC8) 70 . The standard approach was using red cells with rare null phenotypes (null cells) 102–104 to define new blood group systems and new high‐prevalence antigens.…”

“…The first example was the YTEG antigen of the YT blood group system in 2017, 65 followed by the YT antigens YTLI and YTOT 66 and the Indian antigen INSL 84 in 2018. SCAR 70 in the Scianna blood group system 105 and DACY and YCAD 81 in the Knops blood group system 106 were accepted in 2020 based on rBGP evidence without testing against red cells lacking the relevant blood group protein.…”