Autoimmune diseases include a host of conditions where the immune system stops functioning correctly and attacks the body. There are over 100 autoimmune diseases, and most of these conditions attack just one organ—like the pancreas in diabetes or nerve cells with multiple sclerosis (MS)—but some, like lupus, attack multiple organs.
Out of all these various conditions, there is one common thread: Approximately 78% of those with autoimmune diseases are women. The reasons are still being debated, but there are a few key theories that help shed some light as to why women make up the majority.
The consensus from scientific literature is that women have stronger immune systems than men. Women’s higher levels of antibodies and generally higher levels of immune cells make them better able to handle pathogens.
There’s a potential evolutionary reason for this: Infection is the main cause of infant mortality and failed pregnancies. Having a strong immune system can protect the fetus during pregnancy and women can pass on that immunity during breastfeeding. Unfortunately, there’s a price that comes with having a stronger immune system: dysregulation.
The immune system is arguably the most complex system in our bodies. It requires a controlled balance between immune cells that attack pathogens and immune cells that suppress inflammation when a response is not needed. It’s easy to break that delicate balance (dysregulation) and in a very strong immune system, that can lead to the body attacking itself. In other words, autoimmune disease.
Let’s look at several important factors that impact the immune system and can lead to autoimmune disease if they become dysregulated: T cells, hormones, chromosomes, and the gut microbiome. Scientists are debating which of these is the primary driver of immune dysregulation, but likely all are contributors together and explain why women can be so prone to imbalance.
Referred to as the “generals” of our immune system, T cells identify threats and direct the immune system on how to respond. Th1 and Th2 cells are important to keep in balance. An imbalance toward Th1 is necessary for autoimmune diseases like MS, rheumatoid arthritis, diabetes, and psoriasis; while an imbalance toward Th2 is necessary for conditions like lupus.
Another balance involves regulatory T cells (Treg) and Th17 cells. Treg cells suppress the immune system by identifying the self and telling the immune system not to attack it. A healthy Treg system is required to prevent autoimmune diseases. On the other side of the coin are pro-inflammatory Th17 cells. Our bodies produce these to respond to foreign invaders, but they are very damaging, so we want to raise them to deal with issues like bacterial infections but immediately bring them down again once the threat has cleared.
In a healthy immune system, Treg cells dominate and Th17 cells only activate when needed. An imbalance of Th17 cells can lead to autoimmune disease—in fact, chronically elevated Th17 cells precede all autoimmune disorders. What’s worse, Treg cells can convert to Th17 cells and create an imbalance.
Antibodies are another balance that can become dysregulated. Women have higher levels of antibodies, which are critical in fighting pathogens, especially during pregnancy. But, like T cells, they can also become autoreactive and attack the body.
Women go through three major phases throughout their lives that have a big impact on hormone levels: puberty, pregnancy, and menopause. The onset and remission of autoimmune conditions often correlate with one of these three events, thanks again in part to the immune system.
The immune system has receptors for estrogen and progesterone, sex hormones that are more abundant in women. A lot of evidence has shown that these hormones can affect the immune system and cause dysregulation. For example, high estrogen levels reduce Th1 cells and promote the suppressive function of Treg cells. But low estrogen (like during menopause and certain menstrual phases) can cause an imbalance toward Th17 and promote an autoimmune disease. There’s also evidence that women lose some of their ability to produce Treg cells around menopause, which is why women may often get autoimmune diagnoses during perimenopause and menopause.
This is also why women with autoimmune diseases frequently report worsening symptoms during a particular phase in their menstrual cycle but can go into remission during pregnancy. High estrogen protects against many diseases like MS and rheumatoid arthritis, however, some diseases imbalanced toward Th2 cells (like lupus) are exacerbated by high estrogen.
Many of the genes that code for the immune system are on the X chromosome—including genes known to promote autoimmune disorders. Men only have one copy of these genes (XY), but women have two (XX), creating a risk for a toxic double dose of immune expression. To prevent this, the second X chromosome is usually deactivated in women, but sometimes the deactivation isn’t perfect, leading to an immune system on overdrive.
There is a condition where some men have two X chromosomes like women (XXY). Men with this condition have the same rates of lupus as women, when normally women are diagnosed with lupus at a ratio of 9:1 compared to men.
Since most immune cells reside alongside the digestive system, it should come as no surprise that the gut microbiome can play a factor in autoimmune disease. Women have a more diverse microbiome than men, but there is also evidence that the female microbiome can be more inflammatory. Many T cells live around the gut to deal with bacteria, but women’s microbiomes can reduce Treg cells and promote Th17 cells, leading to chronic inflammation.
Scientists are still trying to fully answer the question of why women are more susceptible to autoimmune disease despite all of the evidence above, so unfortunately there isn’t a full answer yet of how to reduce risk. There is also a genetic component, so for some women autoimmune disease may be unavoidable. However, there are still things people can do to reduce the risk of developing an autoimmune disease or help mitigate symptoms if they already have one.
Sixty years ago, the ratio of men and women being diagnosed with MS was almost even. By the 1980s it was 2:1, and by the mid-2000s it was 3:1. The trend toward more women being diagnosed with MS is a recent phenomenon, which could mean recent environmental factors are driving increased susceptibility. Considering the biggest changes in the last 60 years, diet is a strong candidate. Here’s a few things we do know about how diet affects inflammation and autoimmunity:
Salt: A high-sodium diet promotes Th17 cell growth and is known to increase the risk for autoimmune conditions.
Gluten: We only know environmental triggers for three autoimmune diseases and in two of the three (celiac disease and dermatitis herpetiformis), gluten is the trigger. Gluten is known to cause leaky gut, raise Th17 cells, and has been associated with autoimmune conditions like diabetes. In my thesis research with Dr. Loren Cordain, we studied over 100 people with autoimmune diseases. When they went on a gluten-free diet, they even surprised their doctors with their improvements.
Lactobacillus: Administration through tube feeding of the beneficial bacteria Lactobacillus has been shown to reduce gut permeability, restore Treg function, and suppress inflammatory Th17 cells in female mice. Lactobacillus is commonly found in fermented foods.
For those who have already been diagnosed with an autoimmune disease, an elimination diet can help target foods that may trigger inflammatory episodes. Our autoimmune protocol diet involves removing potential triggers such as grains, nightshades, dairy, processed foods, and added sugars for 30 to 90 days, and then gradually reintroducing the foods one at a time to determine which ones cause a response.
Because hormones are one of the potential factors in autoimmune disease risk, anything that can disrupt hormones may also contribute. To quote one study: “Factors that may disrupt the balance between T helper [Th] and Treg cells and induce autoimmune disease include birth control pills, stress, existence or development of ovarian cysts, and overuse of products containing xenoestrogens, etc., causing hormonal imbalance.”
While we don’t want to promote going off your hormonal birth control, it may be a factor to consider discussing with your healthcare provider if you have concerns. On the other hand, stress and xenoestrogens are known to cause a variety of health issues besides autoimmune disorders, and would be good to reduce in order to help improve overall health.
—Trevor Connor
(Billi et al., 2019; Cady et al., 2020; Desai & Brinton, 2019; Gleicher & Barad, 2007; Jr. et al., 2009; Kleinewietfeld et al., 2013; Kronzer et al., 2021; Nie et al., 2015; Veldman et al., 2006; Wu et al., 2013)
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Cady, N., Peterson, S. R., Freedman, S. N., & Mangalam, A. K. (2020). Beyond Metabolism: The Complex Interplay Between Dietary Phytoestrogens, Gut Bacteria, and Cells of Nervous and Immune Systems. Frontiers in Neurology, 11, 150. https://doi.org/10.3389/fneur.2020.00150
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