Women Account for 80% of Total Autoimmune Disease Cases, Doctor Explains the Causes

Walk into a rheumatology clinic and one pattern is difficult to miss: most patients are women. This is not simply a matter of women being more likely to seek medical care or being diagnosed more often. Women genuinely have a higher risk of developing many autoimmune diseases.

Reports suggest that around three-quarters of people living with autoimmune conditions are women. Of the 20 most common autoimmune conditions, 18 occur more frequently in women than men. Conditions such as lupus, rheumatoid arthritis, multiple sclerosis and Sjögren's syndrome show particularly big differences between the sexes.

For lupus, women are affected about nine times as often as men, while Sjögren's syndrome can affect women up to 19 times more frequently.

So, why are women more vulnerable to autoimmune diseases? According to Dr Tushar Tayal, Associate Director - Internal Medicine, CK Birla Hospital, Gurugram, the answer is not a single factor. Genetics, hormones and the way the immune system functions all appear to interact.

Why Are Women At More Risk?

Women have stronger immune responses.

One important clue lies in the way the immune system functions in women.

According to a study published in the journal 'Evolutionary Applications', women generally produce stronger innate and adaptive immune responses than men. This can provide an advantage when fighting infections and can also lead to stronger antibody responses following some vaccinations.

However, a highly active immune system may also increase the possibility of an abnormal immune response in people who are genetically susceptible to autoimmune disease.

“Women do not have weaker immune systems. In many respects, their immune responses are stronger. The potential downside is that this heightened immune vigilance may increase the risk of the immune system mistakenly targeting healthy tissues,” explains Dr Tayal.

How Do X Chromosomes Influence Autoimmune Risk?

The difference is not only about hormones. Sex chromosomes may also play an important role.
Women typically have two X chromosomes, while men generally have one X and one Y chromosome. Because having two active X chromosomes would result in excessive expression of many X-linked genes, one X chromosome in most female cells is largely switched off through a process called X-chromosome inactivation.

This Process Is Controlled In Part By A Molecule Called Xist

A landmark 2024 study from Stanford found that proteins associated with the Xist ribonucleoprotein complex can become targets of autoantibodies in several autoimmune diseases. This provides a possible explanation for part of the increased autoimmune risk seen in women.

Male cells generally do not undergo X-chromosome inactivation in the same way because they have only one X chromosome. However, X-chromosome biology is only one part of the explanation and does not account for all sex differences in autoimmune disease.

Role of Hormones

Hormones, particularly oestrogen, also influence the immune system.

Oestrogen can affect the activity of several types of immune cells and influence the production of antibodies and inflammatory molecules.

This may help explain why some autoimmune conditions develop or change in activity during periods of major hormonal change.

Puberty, pregnancy and the reproductive years can all involve significant shifts in hormone levels. Lupus, for example, commonly begins during a woman's reproductive years.

However, hormones alone cannot explain why women are more at risk. Their effects interact with genetics, immune responses and environmental factors.

Can Pregnancy Affect Autoimmune Diseases

Pregnancy causes major changes in the immune system. Contrary to the common belief that pregnancy simply suppresses immunity, the immune response undergoes a carefully regulated shift to allow the mother's body to support the developing baby.

These changes can influence autoimmune disease activity.

Some women experience improvement in certain autoimmune conditions during pregnancy, while others may notice worsening symptoms. The postpartum period is particularly important because immune and hormonal changes after delivery can trigger the first appearance or a flare of some autoimmune diseases.

This is one reason women with autoimmune conditions require appropriate medical monitoring during pregnancy and after childbirth.

Role of Genetics

Having a genetic predisposition can increase the likelihood of developing an autoimmune disease.

Certain genes influence how the immune system identifies and responds to potential threats. However, having these genes does not guarantee that someone will develop an autoimmune condition.

Environmental factors such as infections, smoking, certain medications, ultraviolet exposure and other triggers may contribute to disease development in genetically susceptible people.
The interaction between genes, hormones, chromosomes and environmental exposures helps explain why autoimmune diseases are so complex.

Does This Mean Women Are Biologically Fragile?

“No, the higher prevalence of autoimmune disease should not be interpreted as evidence that women have weaker or poorer immune systems,” Dr Tayal answers.

In fact, their stronger immune responses can provide important protection against infections.
The same biological characteristics that help women mount effective immune responses may, in some genetically susceptible individuals, increase the risk of the immune system becoming misdirected.

This is better understood as a biological trade-off rather than a weakness.

What Does This Mean For Diagnosis And Treatment

Understanding why autoimmune conditions are more common in women could eventually improve how these conditions are diagnosed and treated.

Recognising sex-specific risk factors may help doctors identify symptoms earlier, particularly in women with a family history or multiple unexplained symptoms.

Research into X-chromosome biology, hormones and immune pathways may also contribute to more personalised treatments in the future.

For patients, persistent symptoms such as unexplained joint pain, prolonged fatigue, recurring rashes, unexplained fevers, dry eyes or mouth, or neurological changes should not simply be dismissed as stress or ageing.

Final Word

Autoimmune diseases affect women more often than men because of a complex combination of genetics, X-chromosome biology, hormones and stronger immune responses. As Dr Tushar Tayal explains, women do not have weaker immune systems. Their generally stronger immune responses can offer greater protection against infections, but in genetically susceptible individuals, this heightened immune activity may also increase the risk of the immune system attacking healthy tissues.