Autoimmune diseases are those when your immune system attacks your body instead of defending it. When your body can’t tell the difference between your own cells and foreign cells, it starts to attack the normal cells which eventually gives rise to autoimmune disease. Johns Hopkins Medicine says that there are more than 80 types of autoimmune diseases that affect a wide range of body parts. Some of the most common autoimmune diseases are rheumatoid arthritis, psoriasis, lupus, Graves’ disease, Hashimoto’s thyroiditis and type 1 diabetes.

A study by Stanford Medicine says that as many as 4 out of 5 people affected with autoimmune diseases are women - “Women have too much of a good thing: It’s called the X chromosome.”

According to a report in Tidsskriftet, it is advantageous for women to have two X chromosomes. Women are protected against X-linked hereditary diseases. “A woman with a defective gene on one X chromosome will most often be unaffected as long as she has a normal copy of the gene on the other X chromosome. The presence of two X chromosomes may be one of the reasons that women generally live longer than men. However, the price of having two X chromosomes is a higher risk of autoimmune disease.”

The biological sex in the mammalian kingdom is determined by the presence in every female cell, of two X chromosomes. Male cells pack just one X chromosome, paired with a much shorter one designated the Y chromosome. The Y chromosome contains only a handful of active genes. It’s quite possible to live a full life without a Y chromosome. However, no mammalian cell, male or female, can survive without at least one copy of the X chromosome, which holds many hundreds of active protein-specifying genes.

Stanford Medicine says that having two X chromosomes risks the production, in every female cell, of twice the amount of the myriad proteins specified by the X but not the Y chromosome. Such massive overproduction of so many proteins would be lethal. Hence, one of the X chromosomes is inactivated. This way the same amount of each X-chromosome-specified protein is produced in a female cell as in a male cell.

The researchers discovered that X-chromosome inactivation can lead to autoimmune disorders, although other factors can also cause these disorders. This also explains why men sometimes develop autoimmune diseases.

Dr Tushar Tayal, Consultant, Internal Medicine at CK Birla Hospital, Gurugram and Dr Mahesh Chavan Sr. Consultant Endocrinology at Apollo Hospitals, Navi Mumbai share how the X-chromosome and other factors make autoimmune diseases more prevalent in women.

A combination of genetic, hormonal and immunological factors make autoimmune diseases more common in women.

The X chromosome which women have two copies of, carries a dense cluster of immune-related genes. Unlike men, who have one X chromosome, women experience unique immune regulatory challenges. One key factor is that certain immune-related genes escape the process of X-inactivation, where one of the X chromosomes in each cell is silenced. This escape leads to higher expression of genes like Toll-like receptor 7 (TLR7), which has been strongly associated with lupus, an autoimmune disease. Also, during pregnancy, foetal cells can persist in the mother’s body which is a phenomenon called microchimerism, potentially triggering autoimmune conditions later in life.

Oestrogen hormone tends to enhance immune responses which is beneficial for fighting infections but can also increase the likelihood of autoimmune reactions. Conversely, testosterone, which is higher in men, has an immunosuppressive effect, offering some protection against these conditions. Fluctuations in hormones during pregnancy, menstruation or menopause further modulate disease activity, with conditions like lupus often flaring during hormonal peaks.

Women generally have more robust immune systems, likely an evolutionary adaptation to protect offspring. However, this heightened immune response increases the risk of the immune system attacking the body’s own tissues. Women also have higher levels of pro-inflammatory cytokines, which may predispose them to autoimmune conditions.

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