University of Michigan and NIH scientists find a biological mechanism to explain the phenomenon
During pregnancy, many women experience remission of autoimmune diseases like multiple sclerosis and uveitis. 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 Howard R. Petty, Ph.D., biophysicist at the University of Michigan Kellogg Eye Center and Roberto Romero, M.D., of the National Institutes for Health. The study, which appears online ahead of print in the August issue of the American Journal of Reproductive Immunology, also reports that expression of the enzyme is lower in pregnant women compared to those with pre-eclampsia, a condition with inflammatory components.
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 Petty. 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.