About 80% Of Autoimmune Disease Cases Are In Women. Experts Explain Reasons Behind Increased Prevalence In Females

Women's Health Month: Autoimmune diseases are the disorders in which one's immune system attacks the healthy cells of organs and tissues by mistake.

Women's Health Month: Autoimmune diseases occur because the immune system cannot differentiate between the body's own cells and foreign cells, and hence, attacks the normal healthy cells. There is a greater prevalence of autoimmune diseases among women, than men.

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Women’s Health Month: Women are more prone to autoimmune diseases than men. Autoimmune diseases are the disorders in which one's immune system attacks the healthy cells of organs and tissues by mistake. These diseases occur because the immune system cannot differentiate between the body's own cells and foreign cells, and hence, attacks the normal healthy cells.

About 80 per cent of all patients diagnosed with autoimmune diseases are women, according to experts.

Why autoimmune diseases are more prevalent in women than in men

There is a greater prevalence of autoimmune diseases among women, compared to men. 

“Autoimmune diseases occur at a rate of 2:1,” Dr Namrita Singh, Associate Director, Internal Medicine, Max Smart Super Specialty Hospital, Saket, told ABP Live.

This means that the prevalence of autoimmune diseases in women is twice that in men. 

“The exact aetiology of autoimmune disorders is said to be unknown. However, autoimmune diseases are often associated with the X chromosome inactivation. A female individual normally has two X chromosomes,” Dr Singh said.

How defective X-inactivation could lead to autoimmune diseases

During early embryonic development in females, one of the two X chromosomes is randomly and permanently inactivated or silenced in cells other than the egg cells (sex cells). This phenomenon, known as X-inactivation, ensures that females, like males, have one functional copy of the X chromosome in each cell of the body. However, X-inactivation is random, as a result of which in normal females, the X chromosome inherited from the mother is active in some cells, while the X chromosome inherited from the father is active in other cells, according to the US National Institutes of Health (NIH). 

X-inactivation is important to prevent the overexpression of genes, and ensures that genes are functional only on one of the two X chromosomes in each cell. 

However, there are cases where some individuals are genetically more skewed toward their maternal X chromosome, while others are more skewed toward their paternal X chromosome. As a result, the body is unable to recognise the opposing X chromosome. This results in an increase in polymorphic antigens, which the immune system views as foreign substances, and elicits an immune response.

“During the early stages of embryonic development, females undergo a phenomenon known as X inactivation, which prevents the overexpression of genes. The genes present on one of the two X chromosomes, in each cell, are silenced. In certain cells, the X chromosome inherited from the mother is inactivated, while in other cells, the X chromosome inherited from the father is inactivated. Some may be genetically more skewed toward their maternal X chromosome, while others are more skewed toward their paternal X chromosome. This leads to the body not being able to recognise the opposing X chromosome, resulting in a rise in polymorphic antigens, which are viewed as foreign substances invading the body. This elicits an immune response, and results in production of antibodies against the assumed foreign substance, ultimately causing the body to attack itself unknowingly,” Dr Singh explained.

She also said that the genes, whose overexpression is prevented by X inactivation, play an essential role in immunity, and code for proteins such as antibodies. Therefore, overexpression will result in an overproduction of antibodies.

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Hormonal changes during menstruation, pregnancy and menopause may lead to autoimmune diseases

Hormonal factors, genetic predisposition, and the interplay between genetics and the immune system may also be responsible for the increased prevalence of autoimmune diseases in women.

“Some autoimmune diseases can be triggered or influenced by hormonal fluctuations during different stages of a woman's life, such as pregnancy or menopause,” Dr. Ankita Chandna, Associate Director, Obstetrics And Gynaecology, Max Super Speciality Hospital, Shalimar Bagh, told ABP Live.

According to Dr Mithee Bhanot, Senior Consultant, Obstetrics and Gynaecology, Apollo 24|7, and Apollo Hospitals, Sector-26, Noida, hormonal changes that occur during a woman’s menstrual cycle, or pregnancy, may trigger the occurrence of some autoimmune diseases.

“Women are more likely to suffer from thyroid issues. Some thyroid issues occur due to the immune system's erroneous attack on the thyroid gland,” Dr Bhanot said.

Autoimmune diseases common in women

Rheumatoid arthritis, psoriatic arthritis, thyroid diseases such as Grave's disease and Hashimoto’s thyroiditis, psoriasis, lupus, and type 1 diabetes are common autoimmune diseases in women, according to Johns Hopkins Medicine. 

Systemic sclerosis, also called scleroderma, is a rare autoimmune disease which can occur in women. It is a group of rare diseases that involve the hardening and tightening of skin, and may also cause problems in the blood vessels, internal organs and digestive tract, according to Mayo Clinic. Scleroderma means hard skin in Greek, and since multiple sclerosis is characterised by the build-up of scar tissue or fibrosis in the skin and other organs, it is also called scleroderma. 

Since the condition is associated with fibrosis, which occurs due to the excess production of a tough protein called collagen, and affects organs other than the skin, the disease is called systemic sclerosis, according to the US National Institutes of Health (NIH). 

Several genes, including a family of genes called the human leukocyte antigen (HLA) complex, IRF5 and STAT4, are associated with an increased risk of developing systemic sclerosis.

“Systemic sclerosis, though rare, is an autoimmune disease affecting the skin and internal organs of patients due to a collagen defect. It affects women in a 3:1 ratio,” Dr Singh said.

She explained that the clinical features of systemic lupus erythematosus are debilitating fatigue, fever, pain, and a butterfly rash seen on the face.

Autoimmune arthritis includes diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjogren's syndrome and psoriatic arthritis.

Systemic lupus erythematosus is the most common type of lupus in which the person experiences widespread inflammation and tissue damage in the joints, skin, brain, lungs, kidneys and blood vessels. 

“Systemic lupus erythematosus, an autoimmune disease in which the body attacks healthy tissues of the skin, joints, kidneys, and the brain, is seen to affect women in a 7:1 ratio. The disease can occur due to an overexpression of CD40LG and CXCR3 genes. This overexpression results from the lack of X inactivation,” Dr Singh said.

The fact that systemic lupus erythematosus affects women in a 7:1 ratio means that the chance of occurrence of the disease in women is seven times higher than that in men.

Sjogren's syndrome is characterised by dry eyes and a dry mouth, and also affects fingers, ankles, knees, and hips. It occurs with other disorders such as rheumatoid arthritis and lupus. The disease occurs due to the degeneration of tear and salivary glands. 

“Sjogren’s syndrome, an autoimmune disease characterised by chronic dry eyes and mouth due to the degeneration of tear and salivary glands, affects women in a 9:1 ratio. The autoimmune disease is linked to a drop in oestrogen levels, a hormone which plays a pivotal part in female immunity. As oestrogen decreases during menopause, its ability to decrease inflammation effectively is also reduced,” Dr Singh said.

She said that both rheumatoid arthritis and Sjogren’s syndrome have increased prevalence in women due to hormonal changes.

Rheumatoid arthritis affects the lining of joints, causing a painful swelling that can result in bone erosion and joint deformity. 

“Rheumatoid arthritis is characterised by painful, swollen, stiff joints, often accompanied by fever, fatigue, and weight loss. It causes chronic inflammation of various joints, which thickens the synovium, restricting movement and flexibility,” Dr Singh said.

The synovium is a connective tissue that lines the inside of the joint capsule, a bubble-like structure that surrounds joints. 

“Those affected by rheumatoid arthritis experience thickening of the synovium due to  inflammation, causing deterioration of cartilage and bone of the affected joints. Women between the ages of 40 and 60 are more likely to develop rheumatoid arthritis compared to men, due to undergoing hormonal changes during menopause. Menopause decreases oestrogen and progesterone levels, which is thought to perform a protective function for bones and joints,” Dr Singh explained.

Psoriatic arthritis can affect some people with the skin condition psoriasis, and causes affected joints to become swollen, st5ff and painful, according to the UK National Health Service (NHS).

Psoriasis is a skin condition characterised by the appearance of flaky, itchy patches of skin which form scales, often results in a rash and mostly occurs on the knees, elbows, trunk and scalp. 

“Psoriasis is an autoimmune disorder characterised by the increased thickness of skin. This hyperkeratosis leads to the formation of red, salmon, and white-coloured scaly, itchy plaques. These plaques can occur anywhere on the skin but predominantly seen on the back, elbows, knees, and scalp,” Dr Singh said.

Abnormal thickening of the outer layer of the skin, which is made up of a protein called keratin, is called hyperkeratosis.

“The skin is severely impacted by the hormonal changes of sex hormones, prolactin, glucocorticoids, epinephrine, thyroid hormone, and insulin. Women typically experience more hormonal changes than men, as well as often contain greater quantities of many of the hormones which directly act as triggers for psoriasis, lending to a potential theory about why more women are likely to develop psoriasis than men,” Dr Singh explained.

Grave's disease is an autoimmune disorder which results in hyperthyroidism, or over-production of the thyroid hormone. The disease is more common in women than in men. 

Hashimoto's thyroiditis causes hypothyroidism, or the reduced production of the thyroid hormone, because cell- and antibody-mediated immune processes destroy thyroid cells, according to the NIH. 

Type 1 diabetes, earlier known as juvenile diabetes or insulin-dependent diabetes, is an autoimmune disease and a chronic condition in which the pancreas produces little or no insulin, a hormone which helps blood sugar enter the cells in the body for use as energy. Without insulin, glucose cannot enter the cells and builds up in the bloodstream, as a result of which the person suffers from different symptoms and complications of diabetes. 

Type 1 diabetes occurs when the immune system destroys the beta cells of the pancreas, which make insulin. As a result, the pancreas stops making insulin.

As experts said, hormonal changes have a great role to play in the occurrence of autoimmune diseases in women. Therefore, one must maintain good lifestyle practices to ensure that the hormone levels remain in check, and the immune system is strong, and does not attack the body's healthy cells. 

Consumption of a diet rich in antioxidants and omega-3 fatty acids, and exercising regularly can help prevent autoimmune diseases.

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