Out of a hundred about one in five people have an autoimmune disease, such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease or thyroiditis.
In them, the immune system mistakenly attacks its own tissues, resulting in an inflammatory reaction that causes tissue destruction.
Autoimmune diseases have become more common in the 21st century with the development of diagnostics and the increase in the average age of the population. In addition, western lifestyles and environmental changes are thought to favor the emergence of some autoimmune diseases.
The autoimmune disease often starts in middle age, and up to 80 percent of those affected are women. The reason for this is unknown, but the female hormone estrogen has been suspected of predisposing to autoimmune diseases. It is also suspected that the cause is related to the X chromosome itself.
Now Stanford University researchers Diana Down lead to confirm at least one X-chromosome-linked mechanism that explains women’s susceptibility to autoimmune attack. It is associated with silencing of the X chromosome.
Unlike men, women have two X chromosomes. In most cells, one of them is partially silenced, because otherwise women would produce an excess of proteins encoded by the X chromosome compared to men. Men’s Y chromosome has much fewer genes.
The X-chromosome is silenced by a molecular cover that binds to it. The cover is formed by the xist-rna strands that are wrapped around the DNA and the proteins attached to them.
Published in the new journal Cell research according to this, it is this mask that incites an autoimmune attack.
One of the new about the authors of the study Howard Chang already noticed almost a decade ago that proteins attached to xist strands attract autoantibodies that attack the body’s own structures.
Now the researchers tested whether this mechanism is important in autoimmune diseases. They produced a strain of male mice whose cells produced strands of the xist protein, unlike male mice in general.
The bands were rendered inoperable in the sense that they were unable to silence the male mice’s only X chromosome.
The male mouse strain used was also an animal model for the rheumatic autoimmune disease, rubella, which causes, among other things, skin symptoms.
Xist-mice producing protein bands were found to be more severely affected by the disease than mice that did not produce these bands. In filamentous animals, more autoantibodies were produced, the defense cells behaved more erratically and the tissue destruction was more extensive.
The same autoantibodies that the mice produced have also been found in women with lupus or other autoimmune diseases.
From this, the researchers concluded that the xist protein strands also incite the human defense system to overreact.
For women the typical autoimmune tendency has gone unnoticed in the past, because the male cell line has been used as a reference point in antibody studies for many decades, says Chang from Stanford University in the bulletin.
Now that the importance of the autoantibodies in question is known, they can be used in the early identification of autoimmune diseases. Autoantibodies are often formed even before the disease causes recognizable symptoms.
Published in Tiede magazine 3/2024.