The Vel blood group system: a review


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American National Red Cross

Subject: Medical Laboratory Technology


ISSN: 0894-203X
eISSN: 1930-3955





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VOLUME 33 , ISSUE 2 (June 2017) > List of articles

The Vel blood group system: a review

Jill R. Storry * / Thierry Peyrard

Keywords : Vel blood group, SMIM1, genotyping, blood group antigen

Citation Information : Immunohematology. Volume 33, Issue 2, Pages 56-59, DOI:

License : (Transfer of Copyright)

Published Online: 09-October-2019



The blood group antigen Vel has been one of immunohematology’s greatest enigmas: the variation in antigen strength from one individual to another, the property of anti-Vel to readily hemolyze Vel+ red blood cells (RBCs), and the difficulty to screen for sufficient numbers of Vel– blood donors had made Vel a tough nut to crack. In 2013, a small, previously unknown protein called small integral membrane protein 1 (SMIM1) was identified on the RBC by three independent research groups using different approaches, and all three groups demonstrated that Vel– RBCs lacked SMIM1. This discovery correlated with homozygosity for deletion c.64_60del in SMIM1 and meant that for the first time there was a universal method to screen for Vel– blood donors. This finding was not the whole answer, however, and an explanation behind the variability in antigen strength was later shown to be due to polymorphism in SMIM1 intron 2, a region that is responsible for gene transcription. Clinically, anti-Vel is important and has caused severe transfusion reactions, although hemolytic disease of the fetus and newborn caused by anti-Vel is uncommon. However, while screening for Vel– blood donors has become easier, the function of SMIM1 is still unknown, and despite its well-conserved sequence across the animal kingdom, the enigma continues.

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1. Sussman LN, Miller EB. [New blood factor: Vel.] Rev Hematol 1952;7:368–71.

2. Sussman LN. Current status of the Vel blood group system. Transfusion 1962;2:163–71.

3. Levine P, Robinson EA, Herrington LB, Sussman LN. Second example of the antibody for the high-incidence blood factor Vel. Am J Clin Pathol 1955;25:751–4.

4. Cedergren B, Giles CM, Ikin EW. The Vel blood group in northern Sweden. Vox Sang 1976;31:344–55.

5. Peyrard T, Pham B, Arnaud L, et al. The Vel– rare blood phenotype in France: a 15-year experience. Transfusion 2010;50(Suppl):28A.

6. Issitt P, Combs M, Carawan H, et al. Phenotypic association between Ge and Vel. Transfusion 1994;34:60S.

7. Haer-Wigman L, Stegmann TC, Solati S, et al. Impact of genetic variation in the SMIM1 gene on Vel expression levels. Transfusion 2015;55:1457–66.

8. Schechter Y, Chezar J, Levene C, et al. ABTI (901015), a new red cell antigen of high frequency. Transfusion 1996;36:25S.

9. Banks J, Poole J, Das Gupta C, Lonicer C, Salama A. Two new cases of anti-ABTI showing an association between ABTI and Vel. Vox Sang 2004;87:38.

10. Storry JR. Five new blood group systems—what next? ISBT Sci Ser 2014;9:136–40.

11. Toivanen P, Hirvonen T. Fetal development of red cell antigens K, k, Lua, Lub, Fya, Fyb, Vel and Xga. Scand J Haematol 1969;6:49–55.

12. Race RR, Sanger R. Blood groups in man. Oxford, UK: Blackwell Scientific Publications, 1975.

13. Dunstan RA. Status of major red cell blood group antigens on neutrophils, lymphocytes and monocytes. Br J Haematol 1986;62:301–9.

14. Storry JR, Joud M, Christophersen MK, et al. Homozygosity for a null allele of SMIM1 defines the Vel-negative blood group phenotype. Nat Genet 2013;45:537–41.

15. Wieckhusen C, Rink G, Scharberg EA, et al. Molecular screening for Vel– blood donors in southwestern Germany. Transfus Med Hemother 2015;42:356–60.

16. Cvejic A, Haer-Wigman L, Stephens JC, et al. SMIM1 underlies the Vel blood group and influences red blood cell traits. Nat Genet 2013;45:542–5.

17. Ballif BA, Helias V, Peyrard T, et al. Disruption of SMIM1 causes the Vel– blood type. EMBO Mol Med 2013;5:751–61.

18. Rink G, Scharberg EA, Bugert P. PCR with sequence-specific primers for typing of diallelic blood groups. Methods Mol Biol 2015;1310:71–81.

19. van der Harst P, Zhang W, Mateo Leach I, et al. Seventy-five genetic loci influencing the human red blood cell. Nature 2012;492:369–75.

20. Christophersen MK, Jöud M, Thuresson B, et al. Genetic variants regulate expression of SMIM1 and the Vel blood group antigen. Vox Sang 2014;107:16.

21. Ulirsch JC, Nandakumar SK, Wang L, et al. Systematic functional dissection of common genetic variation affecting red blood cell traits. Cell 2016;165:1530–45.

22. Christophersen MK, Joud M, Ajore R, et al. SMIM1 variants rs1175550 and rs143702418 independently modulate Vel blood group antigen expression. Sci Rep 2017;7:40451.

23. Arnaud L, Kelley LP, Helias V, Cartron JP, Ballif BA. SMIM1 is a type II transmembrane phosphoprotein and displays the Vel blood group antigen at its carboxyl-terminus. FEBS Lett 2015;589:3624–30.

24. Solyakov L, Halbert J, Alam MM, et al. Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum. Nat Commun 2011;2:565.

25. Issitt PD, Anstee DJ. Applied blood group serology. Miami, FL: Montgomery Scientific Publications, 1998.

26. Mechanic SA, Maurer JL, Igoe MJ, Kavitsky DM, Nance ST. Anti-Vel reactivity diminished by adsorption with rabbit RBC stroma. Transfusion 2002;42:1180–3.

27. Storry JR, Olsson ML, Moulds JJ. Rabbit red blood cell stroma bind immunoglobulin M antibodies regardless of blood group specificity. Transfusion 2006;46:1260–1.

28. Reid ME, Lomas-Francis C, Olsson ML. The blood group antigen factsbook. London: Academic Press, 2012.

29. Rainer T, Israel B, Caglioti S, Figueroa D. The effects of dithiothreitol-treated red blood cells with anti-Vel. Transfusion 2004;44:122A.

30. Duran-Suarez JR. A human anti-Vel enhanced by sodium hypochlorite. Transfusion 2005;26:304–5.

31. Danger Y, Danard S, Gringoire V, et al. Characterization of a new human monoclonal antibody directed against the Vel antigen. Vox Sang 2016;110:172–8.

32. Storry JR, Mallory DM. Misidentification of anti-Vel due to inappropriate use of techniques. Immunohematology 1994;10:83–6.

33. Le Masne A, Vachee A, Horbey C, et al. [Severe form of neonatal hemolytic disease by anti-Vel allo-immunization.] Arch Fr Pediatr 1992;49:899–901.

34. Williams CK, Williams B, Pearson J, Steane SM, Steane EA. An example of anti-Vel causing mild hemolytic disease of the newborn. Transfusion 2005;25:462.

35. Szaloky A, van der Hart M. An auto-antibody anti-Vel. Vox Sang 1971;20:376–7.

36. Becton DL, Kinney TR. An infant girl with severe autoimmune hemolytic anemia: apparent anti-Vel specificity. Vox Sang 1986;51:108–11.