When the Body Attacks Itself
An enormous public health problem originates from an unlikely source: the human immune system. When the immune system turns on the body and attacks itself, the result can be autoimmune diseases like celiac disease or multiple sclerosis. “Collectively, autoimmune diseases affect between 15 and 23 million Americans,” says immunologist Noel Rose, one of the field’s pioneers.
The vast majority of autoimmune diseases have no cure and are seldom diagnosed before major damage has set in. That makes them both hard to treat and hard to understand. “Typically, by the time of diagnosis, many elements of the immune system have been activated, and the original triggering events have been obscured,” says fellow immunologist DeLisa Fairweather (photo above). “If we know the immune factors that help set off one of these diseases, we can tailor therapies or preventatives to moderate those factors.”
Researchers have long known that most autoimmune diseases, such as lupus and rheumatoid arthritis, are triggered when a person with a genetic susceptibility encounters an immune-stimulating factor in the environment, perhaps an infection or a chemical in food. To help find these environmental triggers, and to detail the cascade of immune reactions they cause, researchers have relied on animal models. (The first experimental model of an autoimmune disease, triggered by viral infection, was devised by a team at the School in 1985.)
But the current generation of autoimmune animal models may not be accurate enough. Therapies that slow or stop the autoimmune process in these animals just don’t seem to work as well in humans, says Fairweather.
Typically in these models, researchers provoke an autoimmune reaction with a general immune stimulant known as an adjuvant. This conveniently sends the animal’s immune system into overdrive, but with a pattern of immune activation that may not be representative of human autoimmunity. Fairweather and her colleagues recently developed an adjuvant-free mouse model of myocarditis, a common autoimmune condition that damages the heart. The model appears to be more representative of its human counterpart, and uses the Coxsackie virus to trigger an immune reaction, but Fairweather thinks that other infectious agents and environmental toxins might work as triggers too.
Her myocarditis model also has the advantage of showing different results in male and female mice. A similar gender difference is seen in humans; in fact, about 80 percent of autoimmune disease cases are in women. “Sex hormones such as estrogen seem to cause the immune system to work differently in men and women,” says Fairweather. “That’s an area where much more research is needed.”
With such research, and better animal models, researchers should be able to devise and test more effective treatments, and apply them earlier in the disease course. That can’t happen soon enough because, as Rose explains, “virtually every autoimmune disease we study is increasing in prevalence, and we don’t know exactly why.”