By Dr. John Bartemus, DC, CFMP, Functional Medicine Charlotte, PC. Published August 6, 2026.
Short answer: Roughly four out of five people with autoimmune disease are women, and the reasons are biological, not incidental. The leading explanations are the X chromosome, sex hormones, and sex-based differences in how immune cells behave. A 2026 study from the La Jolla Institute for Immunology added a striking new clue: after analyzing more than 1.1 million immune cells from human lung tissue, researchers found about 1,700 genes that behave differently by sex, many of them on inflammatory pathways. It is a mechanistic step toward answering a question women with autoimmunity have long deserved a better answer to.
If you have an autoimmune condition and you are a woman, you are far from alone, and it is not a coincidence. Autoimmune diseases, in which the immune system mistakenly attacks the body’s own tissue, fall disproportionately on women. Understanding why matters, both for the science and for anyone living with one of these conditions.
How lopsided is the difference?
The disparity is large. Across the roughly 80 to 100 recognized autoimmune diseases, about four out of five patients are women. The imbalance is especially stark in several common conditions: Hashimoto’s thyroiditis, Graves’ disease, lupus, Sjogren’s syndrome, and rheumatoid arthritis all affect women at much higher rates than men. This is one of the most consistent patterns in all of immunology, which makes the “why” so important.
The three leading explanations
Researchers have converged on three broad, overlapping reasons.
1. The X chromosome
Women carry two X chromosomes; men carry one X and one Y. The X chromosome is unusually rich in genes that regulate the immune system. To balance the “dose” of X genes, women normally silence one X in each cell, but this silencing is imperfect, and some immune genes escape it. The result can be a more active, more vigilant immune system, which is protective against infection but also raises the odds of the immune system turning on the body’s own tissue.
2. Sex hormones
Estrogen and other sex hormones are not just reproductive signals; they modulate immune function directly. This helps explain why some autoimmune conditions change with the hormonal shifts of puberty, pregnancy, and menopause. Hormones do not act alone, but they are part of why the female immune system responds differently.
3. Immune cells that simply behave differently by sex
This is where the newest research comes in, and it is the most direct look yet at the machinery involved.
What the 2026 La Jolla study found
In a study published in Nature Immunology, scientists at the La Jolla Institute for Immunology analyzed more than 1.1 million immune cells taken from the lungs of 128 people. The cells they studied are called tissue-resident immune cells. Unlike the immune cells circulating in your blood, these live permanently inside tissue, where they defend against infection and, when they malfunction, can drive chronic inflammation. This distinction turns out to matter a great deal.
Three findings stand out:
Tissue cells are not blood cells. The tissue-resident immune cells behaved very differently from immune cells in the blood, which is significant because most immune research has historically been done on blood. Roughly 1,000 genes were influenced by genetic factors specifically in the tissue cells and were not detected in blood cells.
They carry disease-risk genes. These cells expressed genes associated with genetic risk for both lung disease and autoimmune disease, suggesting they may be part of the path by which a genetic predisposition actually becomes disease.
They differ by sex. The researchers found about 1,700 genes with sex-based differences in expression, and several of these sit on cellular pathways that drive inflammation. Many were more highly expressed in one sex than the other. Because most autoimmune diseases are more common in women, the authors flag this as a possible clue to that long-standing puzzle.
The lung is a logical place to look. Autoimmune diseases such as lupus, rheumatoid arthritis, and scleroderma frequently involve chronic lung inflammation, so the immune cells living in lung tissue are directly relevant to how these diseases develop.
The honest limits
This is a foundational, mechanistic study, and it should be read as one. It maps differences in gene activity; it does not prove that any specific gene causes autoimmune disease or explains the entire sex gap. The lung tissue came from patients undergoing surgery for newly diagnosed lung cancer, which is how researchers gained access to healthy tissue, and the findings will need to be extended to other tissues and larger, more diverse groups. The researchers say plainly that more work is needed. What the study does is powerful but specific: it shows, at unprecedented scale, that immune cells inside human tissue behave differently depending on sex, and it points to inflammatory genes worth investigating next.
The functional medicine perspective: susceptibility is not destiny
Here is the part that matters most if you are living with autoimmunity. Sex and genetics set your level of susceptibility. They load the gun. But whether and how forcefully autoimmunity is expressed is heavily influenced by factors you can act on. In functional medicine we distinguish between the predisposition, which you cannot change, and the triggers and drivers, which you often can.
The modifiable drivers that push the immune system toward a flare are well recognized: leaky gut, food triggers such as gluten, chronic infections, environmental toxins, blood sugar dysregulation, chronic stress, and poor sleep. This is why two women with the same genetic risk can have very different experiences, one with quiet, well-managed autoimmunity and one with frequent flares. The genetics explain why women are more susceptible as a group. The drivers explain much of what happens to a given individual over time.
This is also why a diagnosis like Hashimoto’s, the autoimmune condition behind most hypothyroidism and overwhelmingly a women’s condition, responds so well to a root-cause approach. I explain that in detail in my article on thyroid symptoms with normal labs.
What this means for you
Your experience is real and biological. The female predominance in autoimmunity is grounded in chromosomes, hormones, and immune-cell behavior, not in imagination or oversensitivity.
Susceptibility is not a life sentence. You cannot change your sex or your genes, but you can influence the gut, dietary, infectious, and lifestyle drivers that shape how autoimmunity behaves.
Root-cause work still applies. Even as the genetics become clearer, the practical path forward, lowering inflammation and removing triggers, remains the same.
The science is moving toward you. Studies like this one bring research closer to the lived reality of women with autoimmune disease, which is the first step toward better, more targeted care.
The bottom line
Autoimmune disease hits women harder because of real biological differences: two X chromosomes rich in immune genes, sex hormones that shape immune activity, and, as the 2026 La Jolla study now shows at massive scale, immune cells inside human tissue that behave differently by sex, including on the inflammatory pathways that drive disease. That predisposition is not something you can change. What you can change are the root-cause drivers that determine how loudly your immune system speaks, and that is where the real leverage lies.
Frequently asked questions
Why are women more likely to get autoimmune disease?
About four in five people with autoimmune disease are women. The leading explanations are the X chromosome (women have two, carrying many immune genes), sex hormones like estrogen that modulate immunity, and sex-based differences in how immune cells behave. A 2026 La Jolla study found about 1,700 genes that behave differently by sex in tissue-resident lung immune cells, several on inflammatory pathways.
What did the 2026 La Jolla lung immune cell study find?
Researchers analyzed more than 1.1 million tissue-resident immune cells from the lungs of 128 people. These tissue cells behaved differently from blood cells, expressed genes tied to genetic risk for lung and autoimmune disease, and showed about 1,700 genes with sex-based differences, many on inflammatory pathways, a possible clue to why autoimmune disease is more common in women.
Which autoimmune diseases are most common in women?
Hashimoto’s thyroiditis, Graves’ disease, lupus, rheumatoid arthritis, Sjogren’s syndrome, multiple sclerosis, and scleroderma, among others. Several, including lupus, rheumatoid arthritis, and scleroderma, can also involve chronic lung inflammation.
If autoimmune risk is genetic, can I do anything about it?
Yes. Genetics and sex influence susceptibility, but expression is also shaped by modifiable factors: gut health, food triggers like gluten, chronic infections, environmental exposures, blood sugar, stress, and sleep. You cannot change your genes or sex, but you can influence the drivers that push the immune system toward or away from a flare.
About the author: Dr. John Bartemus, DC, CFMP, is a functional medicine practitioner, educator, speaker, and Amazon international number one best-selling author of The Autoimmune Answer, focusing on autoimmune disease, thyroid disorders, and root-cause medicine through Functional Medicine Charlotte, PC.
This article is for educational purposes only and is not medical advice. The study described is early mechanistic research and does not establish that specific genes cause disease. Discuss autoimmune symptoms and testing with a qualified clinician.
Source: Schmiedel BJ, et al. “Tissue-resident immune cells drive genetic risk in autoimmune and lung diseases.” Nature Immunology, 2026. DOI 10.1038/s41590-026-02596-2. La Jolla Institute for Immunology news release, August 3, 2026. Image credit: pexels-liza-summer-6382648
