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Vel blood group

The Vel blood group is a human blood group that has been implicated in hemolytic transfusion reactions. The blood group consists of a single antigen, the high-frequency Vel antigen, which is expressed on the surface of red blood cells. Individuals are typed as Vel-positive or Vel-negative depending on the presence of this antigen. The expression of the antigen in Vel-positive individuals is highly variable and can range from strong to weak. Individuals with the rare Vel-negative blood type develop anti-Vel antibodies when exposed to Vel-positive blood, which can cause transfusion reactions on subsequent exposures.

The Vel blood group is associated with the SMIM1 gene, which is located in the 1p36 region of chromosome 1. This gene produces small integral membrane protein 1, a single-pass transmembrane protein which carries the Vel antigen but whose structure and function are otherwise poorly understood. The Vel-negative phenotype is inherited in an autosomal recessive manner, being expressed by patients who are homozygous for a deletion mutation in the coding region of SMIM1 which renders the gene nonfunctional. Patients who are heterozygous for this mutation, meaning inherited from only one parent, exhibit weakened Vel antigen expression. Missense mutations at nucleotide position 152 can also result in a weak Vel phenotype, and various single nucleotide polymorphisms in the noncoding regions of SMIM1 affect the strength of Vel antigen expression.

The Vel-negative blood type is rare. The highest prevalence of Vel-negative blood has been reported in Sweden, where approximately 1 in 1200 individuals exhibit this phenotype. Only about 1 in 3000 English people and 1 in 4000 Southern Europeans are Vel-negative, and much lower rates have been reported in people of African and Asian heritage.

When exposed to Vel-positive blood through transfusion or pregnancy, Vel-negative individuals can become sensitized and begin producing an anti-Vel antibody. If they are exposed to Vel-positive blood again, the anti-Vel antibody can bind to Vel-positive red blood cells and destroy them, causing hemolysis. Anti-Vel is a particularly dangerous antibody because it is able to activate the complement system, which causes immediate and severe destruction of red blood cells. Therefore, patients with anti-Vel should not be transfused with Vel-positive blood, as it can cause a serious acute hemolytic transfusion reaction. Finding compatible blood for Vel-negative patients is difficult due to the rarity of this blood type, and it may be necessary to perform autologous blood donation or to contact rare blood banks.

Cases of anti-Vel causing hemolytic disease of the newborn (HDN) have been reported, but this is an unusual occurrence. It is hypothesized that anti-Vel associated HDN is rare because the antibody is usually predominantly composed of IgM immunoglobulin, which does not cross the placenta into the fetal circulation. In addition, the expression of Vel is very weak on fetal red blood cells – particularly in children who are heterozygous for Vel.

Autoimmune hemolytic anemia (a condition in which patients produce antibodies against antigens on their own red blood cells, leading to hemolysis) involving auto-anti-Vel has been reported.

An individual's Vel blood type can be determined by serologic methods, which use reagents containing anti-Vel antibodies to identify the antigen, or by genetic testing. As of 2019, serologic testing for Vel is mainly performed using polyclonal antibodies isolated from the blood of patients with anti-Vel. However, this method is problematic because these antibodies are variable in quality and sometimes produce false negative results in patients with weak Vel expression; moreover, the reagent cannot be mass-produced. In 2016, a recombinant monoclonal antibody against Vel was introduced and it has since been used to screen for Vel-negative blood donors in France. Genotyping of SMIM1 using polymerase chain reaction is another method that has been used to identify Vel-negative donors.

Anti-Vel is a mixture of IgG and IgM immunoglobulins and is able to activate complement, which can cause hemolysis in vitro (i.e. during compatibility testing). Anti-Vel can be mistaken for a typical cold antibody in compatibility testing if inappropriate techniques are used; this misidentification is dangerous, because such antibodies are usually clinically insignificant.

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