Introduction
Autoimmune diseases affect around 1 in 10 people in the UK. However, women are over 85% more likely to be diagnosed with an autoimmune disease than men. An autoimmune disease occurs when the body’s immune system attacks healthy cells, tissues, and organs. Common examples include rheumatoid arthritis, coeliac disease, psoriasis, and type 1 diabetes. The general symptoms of all autoimmune diseases include fatigue, inflammation and/or nerve damage, skin rashes, aching, swollen joints. The non-specific nature and commonality of these symptoms often result in misdiagnosis or dismissal.
To understand why this disparity exists, it is important to consider both genetic and environmental theories, which have been researched extensively. In the following sections, I will explore these theories to shed light on why autoimmune diseases affect women more than men.
The impact of oestrogen
Oestrogen is the hormone produced in the ovaries that promotes the development and maintenance of female characteristics of the body. Studies have shown that females have higher autoantibody responses due to oestrogen. Autoantibodies work the same as regular antibodies, but instead of fighting bacteria and viruses, autoantibodies target healthy tissue and thus are heavily linked to autoimmune diseases. The research suggests that oestrogen increases the activation, survival, mutation, and recombination of B cells, which promotes the higher response of autoantibodies. A study done on mice reflected the correlation between injected oestrogen and increased autoantibody levels.
Oestrogen also decreases the AIRE expression. The AIRE expression is the autoimmune regulator gene, which protects cells from self-reactivity, in particular T-cells. In most people, our body has mechanisms to destroy autoreactive T-cells; however, some often escape this system. The autoreactive T-cells target healthy cells in our body, leading to immune-related damage and inflammation. For example, one symptom of the autoimmune disease multiple sclerosis is vision problems and cognitive changes. Both can be attributed to the damage done by the autoreactive T-cells. The autoreactive T cells damage the myelin sheath in nerve cells, causing harm to the axons. As a result, the messages sent between the nerves and the brain become less efficient.
Having 2 X Chromosomes
X-chromosome inactivation is a process in which one of the two X chromosomes present in females is silenced. Each X chromosome has around 800 protein-coding genes, in comparison to the 107 in the Y chromosome.
X-chromosome inactivation is thus necessary to stop a lethal overproduction of proteins. This process has been found to link to the development of autoimmune diseases due to the role of Xist, X-inactive specific transcript, RNA. Xist is a necessary molecule in X chromosome inactivation. It works by coating one of the X chromosomes, resulting in the silencing of the genes within the chromosome to prevent the coding of proteins. However, in the process, Xist binds to several proteins surrounding the DNA strand. These Xist-protein complexes are what cause the heightened immune response.
A group of scientists, led by Dr Howard Chang at Stanford University, discovered this connection using trials on mice. Two sets of male mice were used: a control group and a biologically engineered group. The biologically engineered group had inserted genes that caused them to produce the XIST molecules. Both sets of mice were then injected with irritants known to induce autoimmune conditions.
The results showed the biologically engineered group was much more likely to develop autoimmune diseases in opposition to the control group.
Potential cures and new research
Unfortunately, there are no current cures for most autoimmune diseases. The treatments that are available mostly focus on managing symptoms and avoiding irritants. However, it is a field that is currently being researched, with some promising developments being made. For example, within the late stages of pregnancy, women with multiple sclerosis (MS) have seen reductions in relapses by 80%. This is more than any drug currently available. It is believed this is a result of the high levels of specific hormones released during this period. This has led to the start of clinical trials to investigate this theory.
Autoimmune diseases as a whole are still widely underfunded and under-researched. However, the evidence is clear that women bear the burden of these diseases. As scientists and researchers try to understand the reasoning behind this trend, this can help improve the understanding of the underlying disease mechanisms. Thus, leading to new treatments and cures as well as improved patient experience. This issue extends outside the realm of autoimmune diseases, with conditions such as endometriosis. Countless medical examples show how women’s health is not being prioritised in research or highlighted in the media. Finding new treatments for autoimmune diseases is not just about scientific pursuit but also about reducing existing health inequalities within our society.
