Anti-U. Should U Worry About It?

What is Anti-U?

Anti-U is a blood group antigen that has gained attention for its importance in blood transfusions and potential complications during pregnancy. Discovered in 1961, Anti-U is part of the MNS blood group system and is relatively rare in the general population. The presence of this antigen can impact the blood transfusion process, particularly for pregnant women of African descent. In this post, we will explore the significance of Anti-U, its association with genotype, phenotype, and race, and the unique challenges faced by pregnant women with this blood group.

Anti-U antibody is an antibody that targets the U antigen, which is part of the MNS blood group system. The MNS system is one of the most complex blood group systems, with over 40 different antigens that can cause an immune response if they are not properly matched during a blood transfusion.

Anti-U and Race

The prevalence of the Anti-U antigen varies across different populations. It is almost entirely absent in individuals of African descent, with only 1-2% of the African population having the U antigen. In contrast, the U antigen is present in approximately 99.8% of people of European origin. Consequently, the incidence of Anti-U antibodies is higher among individuals of African descent, making it an important consideration for blood transfusions and pregnancies within this demographic.

Challenges for Pregnant Women

For pregnant women with Anti-U antibodies, there is an increased risk of hemolytic disease of the fetus and newborn (HDFN). This condition occurs when maternal antibodies cross the placenta and attack the red blood cells of the developing fetus, causing anemia and potentially leading to fetal death or severe neonatal complications. 

Mothers who are identified as having anti-U antibody may require specialized care to prevent HDN. The mother's blood will be screened for the presence of the antibody, and if it is found, she will need regular monitoring of her pregnancy to ensure that the fetus is not affected. This may involve frequent ultrasounds and monitoring of the fetus's blood counts.

If a mother with anti-U antibody gives birth to a baby with the U antigen, the baby may develop HDN, which can cause anemia, jaundice, and other complications. To prevent this, the baby's antigen and antibody status will be checked at birth, and if necessary, the baby may require a blood transfusion with SsU negative blood to prevent HDN.

Phenotype

U- patients are always S- and s-. This S-s-U negative phenotype is due to the patient lacking glycophorin B, which is the RBC glycoprotein responsible for S and s antigen expression. However, not all S-s- patients will be U negative. There exists a variant of the U antigen that produces seemingly incomplete epitopes of the antigen. Figure this similar to partial D patients. This is typically notated as S-s-U+var. Although the U antigen is present on the Red Cell, it has variable missing epitopes and patients can still create an Anti-U towards these missing epitopes were they to come in contact with U+ blood. 

 Acquiring U Negative Blood

In cases where a blood transfusion is necessary for someone with Anti-U antibodies, finding compatible blood can be challenging. The rarity of the antigen, especially among African populations, means that sourcing blood with the U antigen may be difficult. To address this issue, rare donor programs have been established to maintain frozen stocks of blood with the U antigen. These programs facilitate access to compatible blood for those in need, reducing the risk of transfusion reactions.

Many transfusion services will opt to have the unit typed for S and s as well as U, thus patients will often receive S-s-U- blood. Thankfully, as previously mentioned, if the unit is U negative, the unit very well should be S and s negative as well. It is not enough to search for S-s- units, as some may still be U+.

Identifying Anti-U

Care must be taken to properly identify an Anti-U especially in pregnant women., to ensure fetal health and safety. Many people working in a transfusion center Blood Bank may have never seen an Anti-U before, but that certainly depends on the size and population of the hospital. Those working in reference labs would obviously have a higher chance of seeing an Anti-U come through.  

Anti-U initially appears to look like a panagglutinin. Generally all screening cells will be U positive, thus all screening cells will be positive. Additionally, many panels do not have a U negative cell on them. This is lot dependent of course, some do. As such, many panels will also appear as a panagglutinin due to the lack of U negative cells. 

Unless you specifically knew to look for Anti-U, you'd probably be thinking Warm Autoantibody, Daratumumab interference, Anti-k? Who knows. Most people wouldn't think Anti-U. Most hospitals who didn't have a panel with a U negative cell on it would most likely end up sending the specimens to a reference lab for further workup and ID. 

Those lucky enough to have a U negative cell panel will then find it very difficult to rule everything else out, prompting the need for potential send out as well. This is where keeping old expired panels in the back fridge comes in handy. If you can QC a cell and it passes, you're good as gold to use it!

We recently had an Anti-U patient, and despite finding 4 U negative panel cells (current and expired), we still couldn't rule out Jkb,Fya,C,K,E. We had to work with the Red Cross to find S-s-U-Jkb-Fya-C-K-E- blood as we weren't immediately able to send the patient out for workup as they were an outpatient scheduled for OB surgery. They came through with some previously frozen deglycerolized RBCs!