Highlights in this article:
Down syndrome patients are prone to severe infections and autoimmunity including thyroiditis, diabetes, coeliac diseases and alopecia areata. However, the mechanisms underlying autoimmune susceptibility were not well understood. Dr. Bogunovic’s group at Mount. Sinai found increased cytokines, activated T cells and B cells, which works against immune tolerance in Down syndrome patients. They also found that these activated T cells were resolved by the treatment of immunosuppressants. This article shows the potential therapeutic interventions to improve autoimmunity problems in Down syndrome patients.
Background:
Down syndrome is a genetic disorder caused by the presence of an extra copy of chromosome 21. This extra genetic material affects the development of the body and brain, resulting in certain physical and intellectual characteristics. People with Down syndrome may have distinct facial features, such as almond-shaped eyes and a flat facial profile. They may also have health conditions, such as heart defects, hearing and vision problems, and a higher risk of infections. Intellectual and developmental disabilities are also common in people with Down syndrome, though the severity of these conditions can vary widely. With proper support and interventions, however, people with Down syndrome can lead fulfilling lives and make meaningful contributions to their communities.
Down syndrome can cause a wide range of physical and intellectual problems. Here are some of the common issues associated with the condition:
Intellectual and developmental disabilities: People with Down syndrome typically have mild to moderate intellectual disabilities, which can affect their ability to learn and communicate.
Language and speech delays: Children with Down syndrome often have delayed language and speech development, which can make it harder for them to communicate effectively.
Low muscle tone: A condition called hypotonia is common in people with Down syndrome, which can cause weak muscles and difficulty with coordination.
Vision and hearing problems: People with Down syndrome have a higher risk of vision and hearing problems, such as cataracts and hearing loss.
Congenital heart defects: About half of all babies with Down syndrome are born with heart defects, which may require surgery or other medical interventions.
Respiratory infections: People with Down syndrome are more prone to respiratory infections, such as pneumonia and bronchitis.
Digestive problems: Some people with Down syndrome may experience digestive problems, such as constipation, gastroesophageal reflux, and celiac disease.
Immunological problems: People with Down syndrome have an increased susceptibility to infections. This is thought to be due to a combination of factors, including abnormalities in the immune system itself and certain structural differences in the respiratory and gastrointestinal tracts that can make it easier for pathogens to enter the body. People with Down syndrome may also be more likely to develop autoimmune disorders, in which the immune system mistakenly attacks the body’s own tissues. These disorders can range from mild to severe and can affect various organs and systems in the body. Additionally, Down syndrome patients may have a higher risk of developing leukemia, a type of cancer that affects the blood and bone marrow. This may be related to certain abnormalities in the immune system, as well as other factors.
Despite these challenges, many people with Down syndrome can lead fulfilling lives and make valuable contributions to society with the help of appropriate medical care, educational support, and social opportunities.
Discovery:
Autoantibodies have long been associated with various features of Down syndrome, including autoimmune diseases and cognitive decline. In this study, Dr. Bogunovic’s research group identified a predisposition to autoreactivity and delineated the autoantibody repertoire in individuals with Down syndrome. They found that dysregulated immune features, including the cytokine landscape and CD11c+ B cell frequency, were associated with clinical immune manifestations. They also identified an increased frequency of CD11c+Tbet+CD21low B cell population in individuals with Down syndrome, which is implicated in the production of self-reactive antibodies and autoimmune susceptibility. Based on their hypothesis that baseline T cell activation in Down syndrome has an important role in the B cell response, they suggest that resolving basal T cell activation with a Jak inhibitor or IL-6 blockade could be a promising therapeutic avenue to temper hyperinflammation and the autoimmune feed-forward loop described in the study.
For more information:
Nature 2023 2/22
https://www.nature.com/articles/s41586-023-05736-y
Autoimmunity in Down’s syndrome via cytokines, CD4 T cells and CD11c+ B cells
Dr. Bogunovic’s website:
https://icahn.mssm.edu/profiles/dusan-bogunovic