Autoimmunity refers to a pathological immune response of the body's immune system against itself. Autoimmune disease is widely recognized to be significantly more common in women than in men, and often presents differently between the sexes. In addition to gender, race and ethnicity can also play a role in prevalence rates. The reasons for these disparities are still under investigation, but may in part involve the presence of an additional X chromosome in women (given that several genes on the X chromosome are associated with immune system development), as well as the higher presence of female sex hormones such as estrogen (which increases immune system response). The risk, incidence, and character of autoimmune disease in women may also be associated with female-specific physiological changes, such as hormonal shifts during menses, pregnancy, and menopause.
Common autoimmune symptoms experienced by both sexes include rashes, fevers, fatigue, and joint pain. Symptoms which are specific to women include irregular menses, pelvic pain, or vaginal dryness, depending on the given disease. Some diseases such as Graves' disease, rheumatoid arthritis, and multiple sclerosis may improve during pregnancy, whereas others such as lupus may worsen.
Currently, it is not possible to cure autoimmune disease, but many treatments are available. Treatment of autoimmune disease can be broadly classified into anti-inflammatory, immunosuppressive, and palliative – i.e., correcting a functional disturbance related to the condition. Some medications used to treat autoimmune diseases might not be safe to use during pregnancy.
Specific roles of discrimination and disparities may impact women with autoimmune diseases in the categories of race and ethnicity, gaps in research, in workplaces, and in healthcare coverage and treatment. Accommodations can be instituted in workplaces, and homes, to balance disease profiles and conditions .
Common diseases +Autoimmune Disease Cases by SexDiseaseRatio of female:male casesAddison's disease1.5:1Ankylosing spondylitis1:3 – 1:4anti-GBM disease (Goodpasture syndrome)1:2 – 1:9Antiphospholipid syndrome3.5:1Autoimmune hepatitis3:1Behçet's disease1:5 – 2:1Celiac disease1.5:1 – 2:1Crohn's disease1:1 (though F>M after age 25)Dermatomyositis2:1 – 3:1Diabetes type 11:1.8Giant cell arteritis3:1 – 4:1Graves' disease5:1Hashimoto's thyroiditis4:1 – 9:1Multiple sclerosis2:1 – 3:1Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD)1:1Myasthenia gravis3:1 (below 40 years of age)Neuromyelitis Optica (NMOSD)9:1Pemphigus vulgaris2:1Polymyositis2:1Primary biliary cholangitis9:1Primary sclerosing cholangitis1:2Rheumatoid arthritis2:1Sjögren's disease9:1Systemic lupus erythematosus9:1Systemic sclerosis (scleroderma)3:1 – 9:1Takayasu's arteritis9:1Ulcerative colitis1:1 (though M>F after age 45) There are over 100 autoimmune conditions described, of which the majority are more prevalent in women than in men. Approximately 80% of all patients with autoimmune disease are women.
Autoimmune diseases which overwhelmingly affect women include those which affect the thyroid gland (Hashimoto's thyroiditis, Graves' disease), rheumatic diseases (systemic lupus erythematosus, rheumatoid arthritis, scleroderma, and Sjögren's disease), hepatobiliary diseases (primary biliary cholangitis, autoimmune hepatitis), and neurological diseases (myasthenia gravis, neuromyelitis optica spectrum disorders (NMOSD), and multiple sclerosis). For men who may develop these conditions, epidemiological and symptomological differences may still exist. For example, when multiple sclerosis and rheumatoid arthritis do occur in men, they tend to develop later in life for men (around age 30–40) than for women, when incidence rises after puberty.
Some autoimmune diseases affect both sexes at roughly equal rates, or have only a slight female predominance. These conditions include inflammatory bowel disease (ulcerative colitis, Crohn's disease), immune thrombocytopenic purpura (ITP), and MOG antibody disease, among others. Although the lifetime incidence of these diseases may be similar, there may still exist a difference in disease onset, course, complications, and prognosis, which vary based on sex. For example, men are more likely to develop Crohn's disease in the upper GI tract compared to women. Males and females are equally as likely to be affected by Crohn's disease until around age 25, when women become overrepresented as Crohn's disease patients. Women and men are equally likely to develop ulcerative colitis until age 45, after which this shifts to a significant male predominance.
Very few autoimmune diseases are thought to be more common in men than in women. Examples of these may include ankylosing spondylitis, primary sclerosing cholangitis, type 1 diabetes, and certain vasculitides including anti-GBM disease (Goodpasture syndrome) and Behçet's disease (though whether this represents an autoimmune disease vs autoinflammatory disease remains unclear.) On closer inspection, some diseases initially thought to be overrepresented in men have trended towards sex neutrality over time. For example, early studies of ankylosing spondylitis reported a ratio of 10:1 male to female patients, but more recent reports have indicated this is closer to 3:1. This may reflect a true increased incidence in women over time, or may be due to improvements in diagnostic testing.
Additionally, sex ratios of affected patients can vary widely between geographic regions. For instance, Crohn's disease is slightly more common in women in Western countries, whereas it is slightly more common in men in Asian countries. Behçet's disease is more common in males in regions along the historic Silk Road, but is more common in women in the United States. This suggests that the risks of developing autoimmune disease are multifactorial, and may vary based on race and environment as well as sex.
Race and ethnicity Racial and ethnic identities affect prevalence rates in differing autoimmune diseases. For example, lupus, a potential growth of Systemic Lupus Erythematosus and more broadly Lupus Nephritis, is more prevalent in predominately Black, but also Native American, Asian, Hispanic women, and other racial and ethnic minorities in comparison to white females.
Prevalence of lupus for Black women is highest in southern states, and in areas with lower socioeconomic status in the United States. Alongside this, Black women experience more symptomatology and complications related to lupus, including renal disease. In terms of healthcare received, specifically Black women have shown greater frequency in visits to urgent care for autoimmune disease complications, including in Myasthenia Gravis (MG). Black women with MG also develop the condition at younger ages than White women.
For Native American women, autoimmune hyperparathyroidism is more prevalent . In addition, among Caucasian women, celiac disease (or gluten intolerance) is more prevalent than in other races or genders .
Signs and symptoms Autoimmune diseases can result in systemic or localized symptoms, depending on the given disease. Typical systemic symptoms include fevers, fatigue, muscle aches, joint pain, and rashes; these can be seen in diseases such as lupus or rheumatoid arthritis. Other autoimmune diseases have localized effects on specific organs or tissue types. For instance, alopecia areata presents with patchy baldness due to autoimmune destruction of hair follicles, whereas multiple sclerosis presents with neurological symptoms due to autoimmune demyelination of the central nervous system.
Both systemic and localized disease can present with symptoms that are exclusive to women. Women with Sjögren's disease (an autoimmune disease characterized by destruction and inflammation of the salivary and lacrimal glands) are 2–3 times more likely to report vaginal dryness than other postmenopausal women.
Causes The causes of autoimmunity remain the subject of extensive research and include genetic as well as environmental factors. However, the clear overrepresentation of women as persons with autoimmune disease suggests that sex-specific factors are highly instrumental in the development of these conditions. Posited reasons for this disparity include the differential effects of sex hormones (especially estrogen) on immune response, X-chromosome inactivation, changes associated with pregnancy, and evolutionary pressures that affect the sexes differently. Due to biological development, many of these elements are inextricably linked, and it can be difficult to isolate the individual effects of each factor.
X chromosome inactivation
Many genes involved in the immune response reside on the X chromosome, of which most women have two copies, whereas men typically only have one. During cell division in embryological development, one of the two X chromosomes is inactivated at random, in a process called lyonization. This ensures that the expression of X chromosome genes is randomly suppressed on one of the two copies in females to compensate for the extra copy of these genes. Incomplete suppression of the extra copies of these genes may lead to overexpression of some genes involved in the immune response, resulting in a more robust immune response and an increased risk of developing autoimmune diseases.
Additional support for this hypothesis can be illustrated by the higher rates of autoimmune disease in men with Klinefelter syndrome (47,XXY). Like women, males with Klinefelter syndrome also have two copies of the X chromosome, which may predispose them to increased risk of autoimmune disease through the same mechanism. This risk is highest in autoimmune diseases which are female-predominant (e.g., Addison's disease, multiple sclerosis, Sjögren's disease). With the exception of Type 1 diabetes, which affects both sexes at roughly equal rates, Klinefelter syndrome was not correlated with increased risk of autoimmune diseases which occur in males with greater or equal frequency (e.g., ankylosing spondylitis, psoriasis.)
Despite having only one copy of the X chromosome, women with Turner syndrome (45,XO) are still twice as likely as the general female population to develop autoimmune diseases. Interestingly, the autoimmune diseases for which Turner syndrome patients are at greater risk include inflammatory bowel disease, type 1 diabetes, alopecia areata, and several other autoimmune disorders, which tend to affect the sexes at roughly equal rates. This suggests that the development of autoimmune disease is not solely mediated by differential expression of genes on the X chromosome.
Sex hormones