The Vel blood group system: a review

Abstract

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.

Adipose Tissue Epigenetic Profile in Obesity-Related Dysglycemia - A Systematic Review

“…SMIM1 was found to be hypermethylated in MUHO. This gene codifies a protein that is involved in red blood cell formation being also an antigen in the Vel blood group (79). This blood group is more prevalent in individuals of Nordic ancestry and, so far, there is no known connection between this protein and dysglycemia.…”

A challenge for blood management: A patient presenting anti‐Vel antibody undergoing orthotopic liver transplantation

“…In 2013, an unknown protein called "small integral membrane protein 1" (SMIM1) was identified on the RBC membrane, and it was demonstrated that Vel-red blood cells lacked SMIM1. Clinically, anti-Vel is important, with severe transfusion reactions being described, 2 and there is a very limited number of blood donors, with 20-30 known donors and about 50 cryopreserved packed red blood cells in Germany. 3 This patient had previously been transfused more than 5 years ago and had no history of pregnancy.…”