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Evolution could be to blame for our autoimmune diseases, such as lupus, multiple sclerosis and rheumatoid arthritis. For the first time, we have evidence that people who are more susceptible to disorders of this kind are that way because their immune system is better equipped to combat dangerous infections, enabling them to live longer.
“There are so many autoimmune diseases affecting all sorts of tissues,” said Andrea Graham, an evolutionary biologist at Princeton University, at the annual meeting of the International Society for Evolution, Medicine and Public Health in Durham, North Carolina, last month. So what could explain the existence of these conditions? “One potential answer is that vulnerability to immune-mediated disease is simply the price we must pay for potent and rapid defence against infection.”
Graham and her colleagues have found evidence for this idea using a long-running study of elderly people in Taiwan. It has tracked more than 1000 people born between 1892 and 1953 for the past 27 years.
The team analysed blood samples collected from 639 of these people in 2000 and 2006, measuring the levels of “self-reactive” antibodies – those capable of attacking the body’s own tissues. They found that individuals with higher levels of these antibodies were likely to live longer.
For any particular age, the participants with high levels of self-reactive antibodies had on average a 33 per cent lower risk of dying that year. These people also seemed less likely to have a type of chronic viral infection.
The downside is that these antibodies are precisely those implicated in autoimmune diseases. The kidney is one of the first organs to be affected by the autoimmune disorder lupus, so the team also looked at urine samples, which can indicate kidney health. They found that people who had higher levels of self-reactive antibodies may also be more likely to develop lupus.
What makes this study remarkable is that it explains in evolutionary terms why human evolution has failed to weed out autoimmune diseases, says Gabriele Sorci, an evolutionary biologist at the University of Bourgogne in France.
The work was inspired by Graham’s findings from a similar study in the UK that involves not humans but sheep. For the last 30 years, researchers have been painstakingly recording the health and life details of more than 7000 Soay sheep on the Scottish island of St Kilda.
By analysing the antibodies in sheep blood samples, Graham’s team had found that there was a correlation between levels of self-reactive antibodies and those of antibodies against parasites, and that a high level of self-reactive antibodies runs in sheep families. Together, the findings suggest that genetics influences levels of self-reactive antibodies, and that this is linked to mounting a stronger defence against parasites. This seems to provide an evolutionary advantage – sheep with higher levels of self-reactive antibodies live longer.
“Autoimmunity has previously been considered to be a bad thing, and a consequence of the immune system misfiring instead of attacking what it’s supposed to,” says Aaron Blackwell, an evolutionary anthropologist at the University of California, Santa Barbara. “These studies show that there may be a function for autoimmunity,” says Blackwell.
Statistical analysis of the sheep data revealed that the correlation between survival and high levels of self-reactive antibodies isn’t completely explained by being better at beating parasites. This may mean that self-reactive antibodies are not just a side effect of a strong immune system – perhaps they are doing something useful too. Other studies suggest that self-reactive antibodies can help clear dying cells and other debris from the body, and it is possible that they may play a role in watching for cancer cells.
The emerging picture is that physiological responses are a product of long evolutionary processes, and often serve a function that makes an animal more likely to survive under the right circumstances, says Blackwell. “I would expect these results to be applicable across many species and across different human populations,” he says.