Why Women Are More Prone to Autoimmune Diseases and Other Cutting-Edge Research on Autoimmunity
Every month, we get into a different health topic and explore the research. For October, we went through the most compelling new studies on autoimmune diseases, and we’ve got the important takeaways for you.
JCI Insight (2019)
Women are four times more likely than men to have an autoimmune disease. And more than nine times as likely as men to have lupus. The reason for this gender bias has evaded scientists. Researchers have hypothesized that female sex hormones like estrogen may play a role in stimulating the immune system, but others argue that this doesn’t tell the whole story. A new study by researchers at the University of Michigan suggests that part of this story may be told within the skin. Women have previously been shown to have higher levels of a protein called vestigial like family member 3 (VGLL3) in their skin. VGLL3 regulates certain immune-related genes that may play a role in autoimmune diseases.
The Michigan researchers decided to test what would happen if they increased levels of VGLL3 in the skin of mice. Would this cause them to develop autoimmune conditions more easily than control mice with normal VGLL3 levels? After six weeks, mice that had been genetically altered to have higher levels of VGLL3 started to develop thicker skin and scales around their face, a telltale symptom of lupus. They also had significantly higher inflammation and biological markers of early-onset lupus than the control mice. Next, the researchers analyzed skin samples from the mice and compared them to skin samples from humans with lupus. There was considerable similarity in gene expression between the skin of the altered mice and the lupus patients. Identifying VGLL3 as a potential trigger of increased autoimmune diseases among women is the first step—and it’s incredibly exciting. The next step, though, may be a bit more difficult: determining what causes women to have raised levels of VGLL3 and how to stop it from wreaking havoc on the body.
PLOS Medicine (2018)
During pregnancy and breastfeeding, antibodies are passed from mother to baby via the placenta and breast milk. Research within the past few years has also shown that babies get additional immune support from their mothers during vaginal childbirth because they’re exposed to tons of beneficial bacteria that promote the child’s microbiome development. What’s been less understood is whether a mother’s diet can affect a child’s immune development.
A meta-analysis by a team of UK researchers analyzed all existing studies concerning maternal diet and childhood allergies and autoimmune conditions. Across nineteen studies, probiotic supplementation (specifically Lactobacillus rhamnosus) during pregnancy and lactation was associated with significantly reduced eczema among children four years old and younger. Omega-3 fish oil supplementation during pregnancy and lactation was shown to significantly reduce the risk of egg allergies among one-year-olds across six studies. Two studies suggested that omega-3 supplementation during pregnancy may also reduce the risk of peanut allergies. The researchers further found some evidence that breastfeeding for longer periods of time may reduce eczema, wheezing, and type 1 diabetes; however, these associations were not statistically significant.
Repeated stress can have negative effects on not just mental health but physical health, too, as stress has been shown to increase susceptibility to diseases by suppressing the immune system. To determine if there are long-term immune effects due to stress and stress-related conditions, researchers in Sweden studied a cohort of more than 100,000 patients with stress-related disorders such as PTSD over a thirty-year period. They then enrolled siblings of these patients (to control for genetic and familial influence) as well as over 1 million control subjects without stress-related conditions.
They found that patients with stress-related disorders had a 36 percent higher risk of developing an autoimmune disease than the control group. And for patients specifically diagnosed with PTSD, their risk of developing three or more autoimmune diseases was stronger than their risk of developing just one autoimmune disease. However, their risk of developing an autoimmune disease decreased the longer they reported taking SSRI antidepressants during their first year of PTSD diagnosis, suggesting that treatment may have a beneficial effect on autoimmune susceptibility. The researchers also found that the association between stress disorders and autoimmune disorders was stronger among younger patients.
The authors hypothesized that the association between stress conditions and autoimmune disease may be due to biological reasons, such as trauma suppressing the immune system and promoting inflammation, or it could be due to lifestyle factors. For example, people who have experienced significant trauma may have trouble getting a good night’s sleep or they may be more inclined to smoke to help cope, both of which could increase their risk of developing an autoimmune disease.
Nature Biomedical Engineering (2019)
The common thread among autoimmune diseases is that the body’s immune system runs rampant, producing white blood cells and antibodies that attack everything in their path, including the body’s own healthy tissue. Most of the existing medications for autoimmune diseases, like corticosteroids, work by suppressing the immune system broadly. But this can also reduce a person’s natural immunity, making them much more susceptible to serious infections that their body would normally be able to fight off. Ideally, immunosuppressant drugs for autoimmune conditions like lupus or multiple sclerosis would be able to target only the white blood cells and autoantibodies that are causing issues. And they’d leave the healthy immune cells alone to do their job. These sorts of drugs have yet to be developed because the research is still in its infancy.
One interesting area of this research has been on immune checkpoints, which dial up or down the immune response. In a 2019 study, researchers at the University of Utah used a mouse model to test whether programmed cell death protein 1 (PD-1), which is expressed by white blood cells, can effectively modulate the immune system. The researchers designed a protein that targets and kills PD-1 cells, then injected this protein into mice that had experimental autoimmune encephalomyelitis (similar to multiple sclerosis in humans). The protein was able to reduce PD-1 and white blood cells, but surprisingly, it did not affect the mice’s natural immunity. Further research is needed on PD-1 and PD-1-targeting drugs in humans to see if this possible intervention to reduce autoimmunity is better than existing immunosuppressant drugs.