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HLA

Human Leukocyte Antigens

Human Leukocyte Antigens (HLA) are small proteins (called peptides) found 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”. White blood cells act as immune guardians and actively search for HLA markers, removing any cells they find without them.

Our cells have two HLA-DQα markers on their surfaces, with DNA from each parent providing one marker. Everyone (except identical twins) have differences in their DNA, and most of the time, it doesn’t matter too much whether certain sections of DNA are very close or an exact match. However, there are limited options 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 parents’ HLA-DQα means that the HLA-DQα on the placenta is different from the mother’s. 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 prevent the removal of the embryo and make the many essential changes to the placenta, womb, arteries, etc., needed to adapt and support a successful pregnancy.

HLA incompatible pregnancies

When the parents’ HLA markers are too similar (or identical), the HLA-DQα markers of their embryos cannot trigger a normal immune response to pregnancy by the mother. However, there are different possible levels of HLA match unless the parents share exact HLA markers, which affects the possible outcome of the pregnancy:

  • 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 alter to aid conception, and the placenta can’t grow and support a pregnancy.
  • The aggressive Th1 response is triggered with the cells of the placenta seen as invader cells. If the cloaking of the Th2 response isn’t activated, the placental cells will be removed.

As HLA markers don’t change, this is not an issue affecting couples who already have children together.

Testing and treatment

Testing involves karyotype (chromosome) testing of blood samples from both partners. Certain genotypes (i.e. 0501) have a more significant effect on pregnancy. A treatment with lymphocyte immunisation therapy (LIT) has been tried, but it’s not universally accepted.

Advice

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