Why autoimmune diseases are more common in women

An adequate T-cell function is vital as it is responsible for recognizing and neutralizing foreign viruses and bacteria in the body. When there is an influx of T-cells without a virus or foreign bacteria present, the cells will grow restless and begin to attack the host [ 14 ].

SLE is one example of the many different autoimmune disorders affecting women more. Currently, the lack of X chromosome inactivation, causing increased X chromosome activity, is one of the leading theories for the cause for SLE, especially in women.

Each autoimmune disorder varies in regard to the age of onset, symptoms, and overall effect upon those diagnosed. The female predilection of autoimmune disorders follows a bimodal curve as these disorders are more commonly seen in the embryological period or post-menopausal.

VGLL3 elicits a cutaneous inflammatory response in SLE patients such as a butterfly skin rash across their cheeks and nose, by upregulating inflammatory genes [ 16 ]. In the following experiment conducted in which the VGLL3 transcription factor of humans was reviewed under high-resolution global transcription analyses regarding its relation to autoimmune disorders. The experiment analyzed skin biopsies of 31 women and 51 men via whole-genome RNA sequencing.

Essentially, core genetic variations related to immunity were found between women and men, with an upregulation of immune genes in women specifically near the loci of SLE and systemic sclerosis [ 15 ].

Thereby, it was evident that there was a female-biased molecular signature that coincides with increased female susceptibility to autoimmune diseases [ 14 , 15 ].

This molecular signature directly correlates with having two X chromosomes, like in females, causing an upregulation of the VGLL3 gene [ 15 ]. In a separate experiment also conducted on women and female mice, it was observed that compared to men and male mice, female mice and women had increased levels of VGLL3 in their epidermis.

In fact, female mice contained 2. Furthermore, transgenic mice that expressed increased levels of VGLL3 were generated in order to see if SLE-like symptoms would appear in the mice.

Although at birth transgenic and control pups appeared identical, by weeks, those with increased levels of VGLL3 displayed progressive scaling and skin thickening around the same areas humans with SLE would normally display, such as the ears and face. Cutaneous inflammation could also be seen in the transgenic mice, and further experimentation upon their cells revealed increased production of T- and B-cells which caused increased lymphocyte expansion, increased autoantibodies of the B cells along with further tissue damage, as seen in SLE patients [ 17 ].

VGLL3 is present in the epidermis of both men and women. The epidermis is a prime location for VGLL3 as it is the largest organ of the body, a sensitive indicator of immune dysfunction, and the first line of defense against antigens. VGLL3 has a strong correlation to SLE, which presents with characteristics features such as a butterfly rash, discoid rash, photosensitivity, and mucosal ulcers [ 15 ]. It is unclear as to why women contain more VGLL3 in their epidermis, although it has been speculated that it may be due to an evolutionary adaption to help develop a stronger immune system and ward off infection, however, at a great cost [ 15 , 18 ].

Due to the increased amount of VGLL3 present on the epidermis through evolutionary adaption, it has left women with an increased autoimmune response, ultimately causing harmful and often life-threatening autoimmune disorders to manifest [ 18 ]. Thus, via a multitude of factors exclusive to those with two X chromosomes, such as its ability to code for a greater amount of genes due to larger size, X inactivation, as well as an increased amount of transcription factors present in skin, all contribute to crucial genetic biological difference between men and women leading to increased susceptibility of autoimmune diseases in women.

Psoriasis is an autoimmune disorder characterized by the increased thickness of the stratum corneum layer. This hyperkeratosis leads to the formation of red, salmon, and white-colored scaly, itchy plaques. These plaques can occur anywhere on the skin but predominantly seen on the back, elbows, knees, and scalp. This debilitating disorder can often cause a great deal of physical, mental, and emotional stress upon those diagnosed.

Often triggers such as trauma, stress, colder climates, smoking, alcohol, and infections can increase flare-up frequency as well as worsen the symptoms [ 19 ]. Typically, the severity of psoriasis is indicated via the psoriasis area severity index PASI scale, which involves the areas affected as well as the severity of the area affected upon. Women tend to have lower PASI scores in comparison to men. Despite more women being affected by psoriasis, they do not suffer from severe symptoms [ 20 ].

It is unclear as to why men suffer from more severe symptoms of psoriasis. Furthermore, current research has uncovered that hormonal changes often plays a significant role in triggering the onset of psoriasis for many who are predisposed to it genetically or may cause flare-ups of those already diagnosed. This is because the skin is affected directly by the endocrine system and severely impacted by the hormonal changes of sex hormones, prolactin, glucocorticoids, epinephrine, thyroid hormone, and insulin, which are seen in greater quantity or solely in women [ 21 ].

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 as to why more women are likely to developed psoriasis than men.

Rheumatoid arthritis is characterized by painful, swollen, stiff joints, often accompanied by fever, fatigue, and weightless. It causes chronic inflammation of various joints due to the synovium of the joints being compromised.

Typically, the synovium, which is soft tissue lining the joints and tendons, aids with movement, flexibility, and weight impact. Those affected by rheumatoid arthritis experience thickening of the synovium due to the inflammation, causing deterioration of cartilage and bone of the affected joint. It is hypothesized that 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 estrogen and progesterone levels, which is thought to serve as a protective mechanism for bones and joints [ 22 ]. As estrogen decreases during menopause, does its ability to decrease inflammation as effectively, allowing for rheumatoid arthritis to occur. Although women are more likely to suffer from autoimmune conditions, they are also better equipped to overcome infections because of their increased production of antibodies [ 23 ].

Despite being a rare condition, systemic sclerosis is four times more likely to occur in women than men. Women are typically diagnosed earlier on in life, specifically around childbearing age and endure symptoms for a longer duration of time. Like psoriasis, women with systemic sclerosis do not experience severe symptoms when compared to men.

Systemic sclerosis targets multiple systems throughout the body, specifically affecting the skin, joints, lungs, heart, and kidneys. It causes an increased production of collagen with fibrosis, irregular immune system activation as well as vascular abnormalities. Systemic sclerosis, as with other autoimmune disorders, can be attributed to a defect in X inactivation that results in overexpression of many immune regulatory genes [ 24 ].

In an experiment conducted in the University of Pittsburgh regarding estrogen levels and systemic sclerosis, it was found that increased estrogen levels may cause skin thickening and organ fibrosis, hence why women are often diagnosed during childbearing age as estrogen levels increase substantially during pregnancy.

Similar to other autoimmune disorders, systemic sclerosis further demonstrates the predominance amongst women due to a lack of X-inactivation.

Pregnancy results in an influx of hormonal and bodily changes, with hormonal changes continuing until at least one-year post-pregnancy. Such changes serve as a trigger for the development of autoimmune diseases. There are various physiological changes that occur during pregnancy, such as increased basal metabolic rate, lipid levels, and weight gain. Pregnancy will also induce various changes in the levels of hormones such as estriol, progesterone, and prolactin [ 25 ].

The fetus, containing foreign antigens, relies on the mother to serve as its host, resulting in immune changes that tend to cause a suppression of the maternal immune system [ 26 ]. This is believed to be carried out in order to prevent rejection of the fetus but leads to a suppressed immune system, which can certainly trigger the onset of autoimmune diseases. Hormonal changes will also occur during the post-partum period leading to an increased incidence of certain autoimmune diseases, such as rheumatoid arthritis.

Once you have one disease, you are more likely to develop others. What we know in rheumatoid arthritis RA is there is a genetic basis. People who smoke smoking, cigarettes or have periodontal disease are at higher risk. There are two types of bacteria that can lead to RA. Stress can also be a factor.

This is important for women to address as they are busy working, raising families, taking care of parents, etc. To help prevent development of autoimmune diseases symptoms, Dr.

Bakewell recommends eating a healthy Mediterranean diet. Get regular exercise, reduce stress, and get good sleep. Rheumatoid arthritis is an autoimmune disease that involves multiple joints in symmetric fashion.

It affects the hands, feet, and every other joint except the spine. It causes synovitis. This is when excess fluid develops around the joints and becomes thicker. Once the autoimmune response is triggered, there is a cascade effect of autoimmune responses, which could lead to the development of additional autoimmune disorders.

While there is no cure for autoimmune diseases, advancements in medications are providing improved prognosis and patient functionality. Lifestyle modifications may be very helpful in reducing or mitigating auto-immune flare ups.

They include:. Medical treatment options vary for specific diseases, but may include:. The mystery of why autoimmune diseases affect women significantly more than men is multi-faceted, but as science progresses, so does the opportunity for advancement in treatments and for patients to have a better quality of life. Women who experience autoimmune disorders can achieve a high quality of life with a multifaceted treatment team and whole body approach to wellness.

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