An important risk factor for asthma is that your mother also has asthma. However, the basic mechanisms were unclear. A new study now shows that adult asthmatics whose mothers also suffered from asthma have specific epigenetic patterns in their DNA that are not found in asthmatics with healthy mothers. The changes concern especially some immunological signaling pathways. Scientists assume that certain epigenetic patterns that can later lead to asthma are likely to arise during pregnancy.
The basics of our appearance, our skills and our character are encoded in our genes. However, which genes are transcribed and to what extent are regulated by the so-called epigenetic modifications. Under the influence of environmental factors, certain molecules are attached to DNA, causing some genes to be read more, while others are silenced. One of the most important epigenetic modifications is the so-called methylation. The methyl groups of one carbon and three hydrogen atoms bind to parts of DNA and make it impossible to read another gene.
A team led by Kevin Magnaye of the University of Chicago has now studied the methylation pattern in the DNA of asthma patients to find out what role epigenetic changes play in the development of this widespread respiratory disease. As it was now known that maternal asthma is an important risk factor, the researchers compared asthma patients whose mother had asthma to patients whose mother did not have asthma, and to healthy controls. The test material was epithelial cells from the lower respiratory tract of the subjects.
In fact, the researchers found clear differences between the study groups: “Methylation patterns in mothers with asthma were associated with decreased gene expression in signaling pathways in the immune system,” reports Magnaye. Signaling pathways that have been suppressed in asthmatic patients of mothers with asthma are associated with impairment of T-cell signaling. T cells are part of the adaptive immune system and are involved in the immune response to viruses and bacteria, among other things. This suggests that the genetic changes have something to do with asthma, which is characterized by deregulation of the immune system.
Changes already in the womb?
The results on methylation patterns were confirmed in another study that investigated airway epithelial cells in children with asthma. Scientists suspect that the respective epigenetic changes not only occur during life, but are already determined during pregnancy by the fetal environment in the asthma patient’s uterus. “The fact that the results were replicated in a separate cohort of children supports the notion that these changes occur well before adulthood,” says Magnaye’s colleague Carole Ober.
To support this hypothesis, scientists want to accompany the babies of mothers of asthmatics from infancy in future research and track how appropriate epigenetic changes affect them throughout their lives. In addition, the team is currently working on decoding possible interactions between the microbiome, epigenetics and asthma development.
A chance for more effective therapies
The epigenetic changes have been associated with so-called type 2 asthma, a severe form of asthma that does not respond to standard corticosteroid therapy. “This subtype of asthma is especially difficult to treat,” explains Ober. “Our results suggest that the underlying cause is a diminished immune response, which may explain the lack of therapeutic response to corticosteroids.” From Ober’s point of view, this could open up new possibilities for possible therapies. Standard therapy is aimed at suppressing excessive immune responses and thus anti-inflammatory effects. “However, in some patients, immune-boosting therapies may be more effective than immunosuppressive therapies,” the researchers said.
Source: Kevin Magnaye (University of Chicago, USA) et al., Proceedings of the National Academy of Sciences, doi: 10.1073 / pnas.2116467119