In my last post about genetics and inheritance, I asked a question about a family:
a family comes into a clinic for their flu shots and it is found that mom had type AB blood, Dad has type O blood and they have three children with type A, B and type O blood, what are all five people’s probable genotypes and what is the problem?
Genotype Problem
Mom:AB IAIB
Dad: O ii
Child1: A IAi
Child2: B IBi
Child 3: O ii Oops! Where did this kid come from?
After a short discussion, it turns out that Child 3 belongs to one parent from a previous marriage. Which parent’s child is this? If the other parent was homozygous, what was that person’s genotype and phenotype for ABO blood type?
It turns out that blood is even more interesting than this. There is another major blood antigen that needs to be matched when doing transfusions. This antigen is called ‘Rh factor’ because it was initially found in Rhesus Macaques, a type of monkey with a lineage close to our own. Although there are a number of Rh antigens, we are typically referring to the one that elicits the strongest immune response, the D antigen. Blood types are commonly referred to as ‘positive’ if the individual has the D antigen allele or ‘negative’ if the individual does not have this allele.
Like the ABO blood types, the Rh allele is important because of the strong immune response against it after Rh- individuals are exposed to Rh+ blood. Note that this is different than the ABO types where antibodies already exist. People only generate ‘anti-Rh’ antibodies after a primary exposure to this blood type, much like when a person is vaccinated against a disease, exposure to disease-associated antigens initiates the immune response, which will be protective upon later exposures.
This sounds like I am spending too much time in the details, but they are important in this case. To illustrate, let’s discuss the most common situation where this is important:
A woman with type A- becomes pregnant from a man with type B+ blood type.
What ABO blood types are possible from this pairing? Depending upon the genotype of the parents, it could be anything (A,B,AB or O).
But we said that it would be dangerous for blood to mix between someone with A blood type, like the mother, and any type that contained the B antigen, possibly like the baby. So, is this baby in danger?
Thankfully, not. The reason is because the antibodies that we naturally make against the A or B antigens are typically IgM, which are very large molecules that do not pass through the placenta to the baby.
The larger IgM antibody cannot cross the placenta, but the smaller IgG antibodies can
What about the Rh antigen?
The Rh alleles interact in a typical dominant / recessive manner. As you might expect, Rh+ means that you express the protein, and this allele is dominant over Rh-, which means you don’t express this protein. Given this, we know that the mother must be Rh-/Rh- in order for her to have the ‘negative’ phenotype. The man has the ‘positive’ phenotype and therefore must be either Rh+/Rh- or Rh+/Rh+. Either way, the child has a good chance of being Rh+ as well (50% or 100% respectively).
Unlike the antibodies against A and B antigens, antibodies against Rh are typically smaller, IgG molecules. These are capable of crossing the placenta into the child’s blood and can be very dangerous. But also unlike the A and B antigens, anti-Rh antibodies don’t exist prior to exposure, so the mother will not likely have any of these antibodies during her first pregnancy with an Rh+ child.
Because of the nature of childbirth, it is possible that a mother will be exposed to her child’s blood during birth and she may develop antibodies against Rh at this time. But child #1 is already out, so he/she is safe. The difficulty occurs when the mother becomes pregnant with a second Rh+ child. At this time her anti-Rh antibodies can cross the placenta and cause hemolytic disease in the developing baby.
Fortunately, there is a good safety against this. A Johnson and Johnson subsidiary company, Ortho, makes an antibody cocktail called RhoGAM that is given at the 28th week of pregnancy and then again within 72 hours after delivery (now there are a number of similar drugs made by other companies as well). This cocktail contains antibodies that bind to and ‘hide’ any Rh antigen in the mother’s system. In this way, the mother’s immune system never ‘sees’ this antigen and doesn’t make antibodies against Rh, making it safe for her subsequent Rh+ children.1,2
References
- Pregnancy (rhesus negative women) – routine anti-D (review) (TA156) http://guidance.nice.org.uk/TA156
- Rh incompatability. http://www.nlm.nih.gov/medlineplus/ency/article/001600.htm
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