Why are women more susceptible to autoimmune diseases?
The statistics make it clear that autoimmune diseases, such as rheumatoid arthritis, are more common amongst women than men. But what is at the root of this? The international journal Nature breaks down the latest theories, which in the long run may lead to better treatments for everyone, regardless of sex.
Having an autoimmune disease means that the immune system is attacking your own tissue, resulting in inflammation. Common examples of autoimmune diseases are gluten intolerance, type 1 diabetes, multiple sclerosis (MS), and rheumatoid arthritis (RA). The risk of developing RA, which is the most common diagnosis among Elsa’s users, is two to three times higher in women than men.
It is only in recent years that the research has looked more closely at the sex discrepancies in autoimmune disease susceptibility. Most scientists working on sex differences in disease are women, but “we’re making a drive for diversity on all fronts,” Rhonda Voskuhl says, in Nature, July 2021.
Rhonda Voskuhl is a neuroimmunologist at the University of California, Los Angeles, and the president of the Organization for the Study of Sex Differences.
The placenta part of the answer?
Theories about why sex affects the probability of being affected by autoimmune diseases have revolved around both sex hormones and sex chromosomes. The latest theory is based on an advanced combination of hormones, X-chromosomes, and other physiological factors.
Melissa Wilson, geneticist and evolutionary biologist at Arizona State University in the United States, and her research group have taken a holistic approach to the increased risk amongst women by looking at evolution. They have developed a theory from a challenge that only the female body is presented with—allowing a new human body to develop within them without rejecting it as a foreign object.
The body has the ability to regulate the immune system’s activity levels during the different stages of pregnancy. For example, at the beginning of pregnancy when the embryo enters the womb and establishes itself there, the immune system’s activity drops to avoid rejecting this new life. Furthermore, the placenta produces estriol, a female sex hormone that has powerful anti-inflammatory effects.
Fewer and later pregnancies today than before
The system involving the placenta and its functions has evolved over hundreds of thousands of years, and during most of this time, women spent several years in pregnancy.
Nowadays, we are not pregnant as often, and in addition, are pregnant later, which means that we spend less time with a placenta in our bodies. Maybe this shorter period increases the probability of being affected by autoimmune disorders, Wilson and her team suggest.
The theory raises many thoughts and questions. Are women who do not become pregnant—or who have fewer children—at a larger risk of developing an autoimmune disease? Can the age at which they fall pregnant impact this risk? Can an earlier pregnancy have a protective effect? Is there a period in life when it is possible to reduce the risk of autoimmune diseases? In that case, can estriol be used for this?
Purely evolutionarily, it would be a clever move for women to remain healthy during pregnancy. Therefore, theories such as these make sense, says Rhonda Voskuhl, who also highlights the significant strides made in research in autoimmune diseases over the past 25 years. “The future holds great potential for new treatments based on these discoveries,” she predicts.
Why autoimmunity is most common in women, Nature, July 14, 2021