Susceptibility to Autoimmunity- Men or Women?

In this article, I briefly describe the susceptibility to autoimmunity in men and women and compare between the genders.

Table of Contents

What is autoimmunity?

Autoimmunity arises when an organism produces its immune response against its healthy cells and tissues. This type of immune response leads to autoimmune diseases. Hashimoto’s thyroiditis, Graves’ disease, Addison’s disease, rheumatoid arthritis, and multiple sclerosis are some of the prominent autoimmune diseases.

The damage to self cells or organs is done by antibodies alone or T cells alone or sometimes, both by antibodies and T cells. Autoimmunity at a high level is always disastrous, whereas at a low level it provides benefits for an individual. Mammals always use it as a self-defense mechanism for their survival.

The response to autoimmunity in males and females

Autoimmune diseases are more prevalent in the northern hemisphere than in the southern hemisphere of the world. In the United States, nearly 50 million individuals are believed to be living with autoimmunity.

When the comparison is done between males and females, then a study shows that among the 50 million people, 80% are women suffering from autoimmunity diseases. The results thus show that female susceptibility is higher than that of males.

The ratio of affected females to males differs in different diseases

The ratio of females to males affected by autoimmunity varies from disease to disease. In diseases like multiple sclerosis and rheumatoid arthritis, the ratio of females to males affected is 2:1 or sometimes 3:1. But with Hashimoto’s thyroiditis, the ratio highly differs as for every one man, up to nineteen women are affected. This high ratio of females to males has been observed for many years, and there are no specific reasons for this being established.

Enhanced immunity in women

According to research, it has been shown that generally, females clear infectious diseases faster than their male counterparts by mounting sturdy innate and adaptive immune responses. All types of immune activities, like immune cell activation, cytokine secretion after infection, circulating CD4⁺T cells, and mitogenic responses, are all present in higher side in females than in males.

According to some studies based on immunization, both mice and humans show a higher number of antibodies produced in females than their male counterparts. This trend is observed in both primary and secondary responses. This state of enhanced immunity in women makes them more prone to infections and infectious diseases. Women suffer a higher rate of graft rejection in organ transplantation. Thus, women possess a lesser risk of being diagnosed with autoimmune disorders.

Role of sex hormones and the proinflammatory T_H1 responses

Sex hormones also play a vital role in the observed difference in autoimmunity rates between men and women. In the disease systemic lupus erythematosus (SLE), young women at the age of childbirth are more prone as lupus is high due to the elevated estrogen state during pregnancy.

When women enter the state of menopause, a low estrogen level brings an increased rate of remission. Thus, sex hormones play potential regulators of this autoimmune disease SLE. The more female-specific hormones estrogens are associated with elevated immunity, whereas the male-specific hormones androgens are linked with suppression of immunity.

Mice are used as excellent models to study sex differences. The study shows that there is a greater chance for female mice to develop T_H1 responses than their male counterparts. In infections with viruses like vesicular stomatitis virus, herpes simplex virus, and Theiler’s murine encephalomyelitis virus, the proinflammatory T_H1 responses are favorable, thus enhancing the clearance of the viruses.

However, in some cases, proinflammatory responses may have adverse effects. A T_H1 response to lymphocytic choriomeningitis virus (LCMV) leads to more severe disease. Thus, female mice show susceptibility to the virus LCMV and succumb to the disease.

Recent research in mice shows that gut microflora, which has a sturdy influence on systemic immunity, may be affected by sex hormones. Non-obese diabetic mice show a highly female inclination towards the development of spontaneous type 1 diabetes. However, germ-free non-obese diabetic mice do not show such sexual dimorphism towards the development of diabetes. The female non-obese diabetic mice are protected from diabetes by the transfer of male-specific microbiota to their guts.

Does pregnancy play a vital role in developing autoimmunity in women?

According to a hypothesis, the pregnancy and childbearing process in women increases the risk of autoimmunity in them. During pregnancy, the fetus is like a foreign semi-allograft, which the mother has to tolerate inside its body. The female immune system during this time goes through important alterations for successful implantation and development of the embryo.

Normally, females mount more T_H1 responses than T_H2 responses. However, during pregnancy, females mount more T_H2 responses. It may be because of an induced anti-inflammatory environment by pregnancy-linked sex steroids. Thus, T_H2 responses spur diseases like systemic lupus erythematosus (SLE), which possesses a sturdy antibody-mediated component that can worsen during pregnancy. But, diseases like rheumatoid arthritis and multiple sclerosis, which involve inflammatory responses, get improved during pregnancy.

During pregnancy, there is an interchange of cells takes place between mother and fetus, thus establishing a state of microchimerism. It is believed with limited proof that long-lasting maternal cells in offspring and allogeneic fetal cells in the mother may play a role in the development of autoimmune diseases.

Autoimmunity is seen more commonly in women after their childbirth. Women, after giving birth to their child, when affected with autoimmune diseases like multiple sclerosis, Hashimoto’s thyroiditis, and Grave’s disease, show higher rates of fetal microchimerism. The presence of these fetal cells can be observed in peripheral blood along with multiple organs, and plays a supportive role in wound healing, tissue regeneration, and inflammation. Whether fetal cells participate in developing maternal autoimmune diseases is still not clear. However, along with pregnancy, women suffer from multiple disorders.

Conclusion

Susceptibility to autoimmunity – Men or Women? The answer to this question lies in the fact that women are more susceptible to autoimmunity than their male counterparts. A state of enhanced immunity in women makes them more prone to infections and infectious diseases.

Sex hormones play a crucial role in the observed difference in autoimmunity rates between men and women. It is believed that both the pregnancy and childbearing process in women increases the risk of autoimmunity in them.