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Down syndrome and risk of autoimmune diseases

In 2011, the United Nations General Assembly designated March 21 as World Down Syndrome Day. The purpose was to raise public awareness of the issue and to remember the inherent dignity of people with Down syndrome. The initiative also sought to highlight the importance of their individual autonomy and independence, in particular, the freedom to make their own decisions.

Currently, their inclusion in the educational system and improvements in public health have made their life expectancy increase significantly to more than 65 years, for which it is necessary to undertake studies to improve their quality of life.

In particular, people with Down syndrome have a markedly different incidence rate for certain diseases than the rest of the population. While they are more protected against certain pathologies, like most solid tumors, they are highly predisposed to developing other ailments, such as Alzheimer’s disease and autoimmune disorders – in which the immune system mistakenly attacks healthy tissues -, such as diabetes type I and celiac disease, among others.

A study by the Center for Research in Clinical Biochemistry and Immunology (Cibici), an institute that depends jointly on the National University of Córdoba (UNC) and the National Council for Scientific and Technical Research (Conicet), in Argentina, characterized all these institutions as comprehensively alterations of immune cells. The study showed that people with Down syndrome – even if they are healthy – have a hyper-reactive immune system: they behave all the time as if they were fighting a viral infection. It is precisely this characteristic that would explain their greater risk of suffering from autoimmune diseases.

The research was carried out by Paula Araya, as a doctoral thesis, under the direction of Mariana Maccioni, a researcher at Cibici.

The research team has determined why people with Down syndrome are at high risk for autoimmune diseases. (Photo: UNC)

Down syndrome is caused by an extra copy of chromosome 21, which is why it is also known as “Trisomy 21” 1. It is the most common genetic abnormality in the human population, with approximately one case in every 700 people born alive. The choice of 03/21 as World Down Syndrome Day just alludes to trisomy: 3 copies of pair 21.

Many genes involved in the immune response reside on chromosome 21, including four of the subunits that make up the receptors for the interferon family.

“These molecules play an essential role in defense against viruses. In fact, any cell in the body can produce them in the event of a viral infection. Furthermore, interferons play a fundamental role in promoting an antitumor immune response, to give an example ”, explains Investiga Maccioni, director of the study, to Argentina.

The findings of the work showed that people with Down syndrome, even if they are healthy, have a hyper-reactive immune system, difficult to be controlled by physiological regulatory mechanisms. This hyperresponsiveness would be associated with the activity of these triplicate genes, which are on chromosome 21.

“We observed a clear correlation between the marked activation of the T cells of individuals with T21 and the exacerbated response that they manifest. As if they were fighting a viral infection on a sustained or chronic basis. The most striking thing is the inability of the immune system to stop this hyperarousal, which could explain the increase in the incidence of autoimmune diseases (characterized by exacerbated responses of the immune system) and the lower incidence of solid tumors in this population ”, explains Maccioni.

These findings reveal opportunities for therapeutic intervention to modulate cell function and improve health outcomes in people with Down syndrome.

“Knowing the causes of this different pattern of susceptibility to diseases would help us not only to improve the quality of life of people with Trisomy 21, but also to learn about new aspects of these pathologies, which the rest of the population also suffers,” adds Maccioni. .

Characterizing a cell involves exhaustively evaluating its “characteristics” or “properties”, to get an idea of ​​how it is working. The more modern the technology used, it is possible to identify more subtle differences within the same population of cells, in this case, T lymphocytes.

T lymphocytes are fundamental cells of the immune system, they are a type of white blood cell that circulates in the blood. “Before, with ordinary microscopes, all white blood cells looked similar, but as we use more modern technologies we can see how different they are,” explains Maccioni. And he adds: “Many variables of the T lymphocytes are then analyzed simultaneously and then complex statistical analyzes are made to see the differences that exist between the T lymphocytes of a person with trisomy and a control person.”

Regarding the procedure, the researcher explains: “What is done is taking people’s blood, purifying the white blood cells and the first thing we look at is a series of markers present on the surface of the cell, approximately 15 markers through a technology called flow cytometry. We also purify them and carry out cell cultures where we confront them with different stimuli to see how they proliferate, what substances they release, how they react. Always comparing it with the same cell type of the controls of the same age and gender ”.

This research was carried out in collaboration with Joaquín Espinosa, associate director of the Linda Crnic Institute for Down Syndrome, an Argentine researcher living abroad, and was partially subsidized by the MINCyT, PICT-RAICES. In addition, it has been published in the prestigious academic journal PNAS (Proceedings of the National Academy of Science of the United States of America), with the title “Trisomy 21 dysregulates T cell lineages toward an autoimmunity-prone state associated with interferon hyperactivity”.

The research group began a collaboration in Argentina with Cecilia Montes, head of the Medical Genetics Service of the Hospital de Niños de la Santísima Trinidad and with other researchers from Córdoba interested in the subject: Pablo Helguera and Lucas Sosa, and more recently with the otorhinolaryngologist Carina Valeriani.

In this framework, the doctoral thesis Jeremías Dutto will analyze the cells of the immune system that circulate in the blood of girls and boys with Trisomy 21 who attend the Hospital to understand how interferons promote hyperactivity of cells. (Source: Argentina Investiga)

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