Our bodies under attack

The numbers of autoimmune disease diagnoses have been rising in recent years and women are disproportionately affected.

An estimated 75 per cent of those with an autoimmune condition diagnosed are women and researchers want to know why.

When it’s working well the immune system is a tour de force of disease resistance, battling to protect us against viruses, bacteria and any perceived threat to our health. But what happens when it goes awry?

The prevalence of autoimmune disorders — in which the immune system turns on itself and mistakenly attacks healthy tissue — has increased sharply in recent decades. These often debilitating and generally lifelong conditions are responsible for chronic inflammation and other serious symptoms.

Many of the 80 recognised autoimmune conditions — including type 1 diabetes, coeliac disease, psoriasis, rheumatoid arthritis, Crohn’s disease and multiple sclerosis — are spiralling and experts fear they will reach a scale of epidemic proportions.

A report published in November last year by Connect Immune Research, a group of medical research charities including the British Society for Immunology and the MS Society, says these “rapidly rising rates of autoimmune conditions” cost billions. The prevalence of some autoimmune conditions, it says, is increasing by as much as 9 per cent a year.

Karen Addington, UK chief executive of JDRF, the leading global organisation funding type 1 diabetes research, says the “alarming and unexplained rise in autoimmune conditions is causing pain, difficulty and lost opportunities in work and life”. A confounding factor is that an estimated 75 per cent of those with an autoimmune condition diagnosed are women.

While research is under way to explain the sudden prevalence, and why women are disproportionately affected, theories are plentiful.

“We’ve seen an increase in the ratio of women to men with many autoimmune conditions and we don’t really understand the reasons why this is the case,” says Susan Kohlhaas, director of research at the MS Society. “There could be environmental factors involved and there are genetic factors as autoimmune diseases can run in families, and in collaboration with other organisations we are embarking on investigations to find out more.”

A Swedish study published in the Journal of the American Medical Association last year showed that, in men and women, having a stress-related condition can increase the risk of autoimmune disease. Others have suggested that changes in the human microbiome — the ecosystem of microbes that live mostly in the gut and are thought to help to control our immune systems — may be contributing. Rachel Byng-Maddick, a consultant rheumatologist at the Bupa Cromwell Hospital, says bacteria involved in gum disease are associated with rheumatoid arthritis, which “means flossing and good oral health are important in terms of prevention”.

Among the most intriguing theories about why women are so disproportionately affected came in a paper published in the journal Trends in Genetics this month. In what she dubbed the “pregnancy-compensation hypothesis”, Melissa Wilson, an evolutionary biologist at Arizona State University, suggested the placenta was at the root of the reason women’s immune systems are more prone to backfiring. Her theory is that, as hunter-gatherers, women — like all placental mammals — evolved to carry offspring for much of their reproductive life and that their immune systems became super-strong to protect them.

“It was not unusual for women to have 10 or 12 babies and to start having them at a young age,” Wilson says. “And the female body evolved to cope with those demands, with the placenta effectively sending messages to down-regulate the maternal immune system during pregnancy so that the foetus is not rejected.”

But turning down the immune system too much brings other risks, such as the threat of bacteria and viruses that could damage an unborn infant. “So it became a compensatory situation, with some give and take so that the maternal body was still protected. A woman’s immune system became primed to defend them in anticipation of pregnancy,” Wilson says.

According to Wilson’s theory, the trend away from having several babies has resulted in some women’s immune systems going haywire, seeking out anything to attack, including a healthy body.

“Until the last century or so a woman’s immune system expected to be managing a placenta,” she says. “It’s only in the last 100 years that we’ve changed our pregnancies and our environment, and it could be that now the placenta doesn’t have that kind of exposure things have started to go wrong.”

She does not propose women have multiple pregnancies to avoid autoimmune disease. “Pregnancy can be risky in itself and women’s immune systems have evolved to mean they have lower rates of cancer than men,” Wilson says. “But the discovery could herald a new framework for testing how best autoimmune conditions can be treated.”

For the next phase of her research, Wilson hopes to analyse data from the UK Biobank to find out whether women with a greater number of children have lower rates of autoimmune disorders. “We also want to see if having pregnancies later or earlier in life makes any difference to the prognosis. Our aim is to look at the full reproductive history of women and to see if there are any pathways that allow their immune systems to respond in different ways at different stages of their lives.”

She and her colleagues also will look at the protective role of female hormones. “We know that different types of oestrogen have different effects on the body,” Wilson says. “It is the kind called oestriol, only produced during pregnancy, that is protective against autoimmune disease.”

It has long been accepted that during the second half of pregnancy, when the placenta pro­duces oestriol, women with autoimmune diseases have reduced relapses from autoimmune conditions. This protection during pregnancy has been observed in female patients with psoriasis, MS and rheumatoid arthritis.

It has led scientists to think oestriol could be a potential treatment for the dis­orders. A 2015 study at the Univer­sity of California, published online in Lancet Neurology, showed that taking the hormone as well as their conventional medications helped to reduce relapses in patients with MS.

“What we want to find out is whether timing of pregnancies has an effect and if it matters at what age you have children,” Wilson says.

“If we discover that earlier pregnancies offer greater protection, then it could mean you simply get a shot of oestriol at age 13 and you are better protected against autoimmune conditions.”

Her work is part of a whole range of studies investigating the gender bias, including studies funded by the MS Society investigating the role of specific immune cells during pregnancy.

“Researchers are trying to identify immune cells that are active or inactive during pregnancy,” Kohlhaas says. “If we can pinpoint those it would really help advance our understanding.”

Different stages of a woman’s reproductive life also warrant more study, she says. “There are fewer children with many autoimmune conditions, but the menopause and later life is really under-researched and it will be very interesting to see if the significant hormonal changes then play a role.”

What really matters in terms of future treatment options is the interplay between these and so many other factors.

“Some people are genetically more susceptible to autoimmune disease if exposed to environmental triggers,” Byng-Maddick says.

“Bacterial infections, hormones, diet, obesity, smoking and the Epstein-Barr virus can all be implicated in autoimmune function and they could be the reason for higher rates of disorders in women and lower rates in men. As yet we don’t know, but all of the new research is promising and brings hope.”

The Times