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Human Leukocyte Antigens (HLA) are small peptide proteins on the surfaces of all cells, and their function is to identify each cell as “self” to the immune system. Foreign cells (germs, viruses or parasites) don’t carry a person’s HLA on their surfaces, and the immune system sees them as “non-self”.

The immune guardians of the body are the white blood cells, and they actively search for HLA markers and will remove any cells they find without them. Each of our cells has two HLA-DQα markers on its surfaces, with one marker coming from each parent in the DNA package.

Everyone (except identical twins) has differences in their DNA, and most of the time, it doesn’t matter if certain sections of DNA are very close or an exact match, but limited options exist for HLA-DQα markers. When the match between the mother and the baby is too close or identical, it can cause significant problems with the self’/’non-self” recognition system.

Most pregnancies

In most conceptions, the differences in the parents’ HLA-DQα create differences in the HLA-DQα of the placenta to the mother’s markers. This difference allows the mother’s immune system to recognise the pregnancy as “foreign” and start a normal aggressive (Th1) response (see the immune system) to the pregnancy. A suppressive (Th2) immune response soon follows, which involves a blocking antibody that attaches to the placenta, which “cloaks” the pregnancy from a full Th1 (aggressive) response that would terminate it.

Having both sides of the immune system activated enables the mother’s body to make the many essential changes to the placenta, womb, arteries, etc., needed to adapt and support a successful pregnancy without the removal of the embryo.

HLA incompatible pregnancies

When the parents’ HLA markers are too similar (or identical), the HLA-DQα markers of their embryos can’t trigger the normal immune response to pregnancy from the mother. However, unless the parents share exact HLA markers, different possible levels of HLA match  can occur, which affect the possible outcome of pregnancies:

  • The pregnancy proceeds as normal
  • The fetus isn’t recognised fully, and the usual Th1 and Th2 responses don’t happen. The womb lining doesn’t adapt to aid conception, and the placenta can’t grow or support a pregnancy
  • The aggressive Th1 response is triggered by the placenta cells, and they’re seen as invaders. If the cloaking of the Th2 response isn’t activated, the placental cells will be removed

As HLA markers don’t change, this issue cannot affect couples who already have children together.

Testing and treatment

Testing involves karyotype (chromosome) testing with blood samples from both partners, and some genotypes (i.e. 0501) have a greater impact on pregnancy. Treatment with lymphocyte immunisation therapy (LIT) has been tried, but it’s not universally accepted.


  • For couples with a 100% match, the advice is to use donor sperm or surrogacy
  • Screening for other immune sensitivity is recommended as HLA compatibility can trigger other immune-system problems

Photo by Kai Dahms on Unsplash