Now, scientists have described a biological mechanism responsible for changes in the immune system that helps to explain the remission. The expression of an enzyme known as pyruvate kinase is reduced in immune cells in pregnant women compared to non-pregnant women, according to scientists of the University of Michigan and NIH.
The study is significant because the newly discovered mechanism points to a pathway that could be targeted for treatment. “It may be possible to design drugs that mildly suppress pyruvate kinase activity as a means of replicating the immune status of normal pregnancy,” says Howard R.Petty, biophysicist at the University of Michigan.
In addition to pre-eclampsia, he believes that rheumatoid arthritis, type 1 diabetes, and uveitis may eventually yield to similarly designed drugs.
In his search to explain the phenomenon, Petty knew to look for a metabolic pathway or mechanism with two characteristics. It had to “dial down” the intensity of the normal immune response, an action needed so that a pregnant woman does not reject the fetus, which has proteins from the father that are “foreign” to the mother. At the same time, such a mechanism must support cell growth needed by the developing fetus.
The activity of the enzyme pyruvate kinase—and and its product, pyruvate—fills both roles: promoting cell growth while modifying the immune response. Because pyruvate kinase activity is depressed during pregnancy, cell metabolism supports an increased production of lipids, carbohydrates, amino acids, and other substances that support cell growth.
Petty explains that our normal robust immune response depends upon pyruvate to promote calcium signaling, which, in turn, stimulates the production of messenger molecules called cytokines. When pyruvate is decreased during pregnancy, calcium signaling is also reduced, and the immune response is different than that in non-pregnant individuals. Says Petty, “Modification of signaling along this pathway allows the pregnant woman to maintain an immune response, but at a level that will not harm the fetus.”
The study included 21 women in their third trimester of a normal pregnancy, 25 women with pre-eclampsia, and a control group of non-pregnant women. Petty and colleagues used a variety of methods to confirm their findings, including fluorescence microscopy and flow cytometry, which are used to study cell signaling.
MEDICA.de; Source: University of Michigan Kellogg Eye Center