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Johns Hopkins Health - Winning the Battle Within
Issue No. 22
Issue No. 22
Winning the Battle Within
Date: October 15, 2013
The field of autoimmunity is complicated and fast-moving, but innovations are changing the way we think about these diseases and, ultimately, how to stop them
When Noel Rose, M.D., was in medical school in the 1950s, no one talked about autoimmune disease. The concept simply didn’t exist.
“We were taught that the immune system only responded to viruses, germs or other foreign invaders,” Rose recalls. “It seemed logical enough at the time. Why would the body need to respond to itself?”
The young student, however, was curious about just how the immune system engineered these responses, and he and his colleagues soon made a startling discovery: In some cases, the immune system would turn on itself, attacking healthy cells and organs.
The concept of autoimmunity—an immune response directed at the host body—was firmly established in humans. And with it, the concept of autoimmune disease, a disorder caused by that same response.
Now, decades later, Rose is the director of the Center for Autoimmune Disease Research at Johns Hopkins, and he believes more paradigm-shifting discoveries are on the horizon. “Except for the first years when we got the field started, this is the most exciting time for me,” he says. “We’re beginning to see that real treatments and real cures are possible.”
What We Know
More than 80 diseases can be classified as autoimmune, including type 1 diabetes, multiple sclerosis (MS), lupus, rheumatoid arthritis and, the most common, Hashimoto’s thyroiditis. Approximately 50 million Americans, or one in five, suffer from these and other autoimmune diseases, according to the American Autoimmune Related Diseases Association. For reasons not fully understood, 75 percent of those affected are women.
We also have more knowledge of how these disorders are linked; how they can be treated; and, tantalizingly, how an awareness of the body’s responses to autoimmune diseases might lead us to new ways of fighting other conditions, including cancer.
“We now realize the immune system is adaptive,” Rose says. “It learns to recognize pathogens that come along, and new ones are coming along all the time.” Those could be this year’s strain of influenza or the coronavirus that causes Middle East respiratory syndrome.
To help with this recognition process, the body develops receptors on the surface of lymphocytes—the cells that function as the sentries of the immune system.
“As we develop a greater variety of receptor cells, scanning for a greater variety of new pathogens, some of these will inevitably react to something in our own bodies,” Rose explains. “For many of us, this happens at a low level, and it’s perfectly harmless. But for about 80 or so types of diseases, it is not harmless. For one reason or another, this natural response gets out of control.”
Investigators at Johns Hopkins have made some surprising discoveries, often through an integrative approach that allows researchers studying, say, MS to share and collaborate with their Johns Hopkins colleagues doing work in rheumatoid arthritis or lupus, as well as those doing basic autoimmune research.
That multidisciplinary approach to autoimmune disease helps in another, often frustrating aspect: diagnosis. This, Rose concedes, is “an extremely great challenge.” The reason is that many autoimmune diseases start with vague symptoms that don’t become clear until weeks or months later. “Fatigue—a state of total exhaustion, where the patient is unable to conduct daily activities—is a typical early warning sign,” Rose says. “But that could be a symptom in any autoimmune disease, or it could be a sign of other types of disease, including malignancy and chronic infection. So, often, you have to wait.” That, he acknowledges, is frustrating “to the physician as well as the patient.”
That said, the ability to diagnose faster and more precisely is improving. This is especially true at Johns Hopkins, where individuals working in different areas and departments share their knowledge to advance the health of their patients, as well as their understanding of autoimmune disease. Rose says he knows of many people who have some form of autoimmune disease who received a faster diagnosis and more effective treatment because of Johns Hopkins’ closely networked community of physicians and scientists. “We compare notes on research,” Rose says, “and that carries into our clinical practice as well.”
One of the most striking recent insights is that when the immune system does begin to turn on the body, it’s not firing at random. It seeks specific targets. “The old idea is that there’s an immune system run amok, and it starts indiscriminately targeting things in the body,” says Antony Rosen, M.D., director of the Division of Rheumatology. “What we’re coming to understand, however, is that it’s actually targeting things with incredible specificity.”
And in some cases, it seems, the targeted cells are ripe for attack. Rosen cites the condition known as myositis, a general class of autoimmune diseases—such as dermatomyositis, polymyositis and juvenile myositis—in which the immune system damages muscle.
“Patients present with symptoms of muscle weakness,” Rosen says. “They’re unable to lift their arms over their heads, and large muscle groups become weak.”
On the surface, it looks as if much of their musculature has been compromised. But Rosen and his Johns Hopkins colleagues have learned that it’s not quite the blunt assault. “Very few molecules are attacked, and they are very specific,” he says. What’s more, “the levels of fuel in these cells are high.”
In other words, the immune system appears to deliberately target the cells that can make the condition worse.
Connections to Cancer
The targeting of specific cells may help to explain why a striking 20 percent of people who have autoimmune diseases go on to develop cancer. That worrisome statistic, however, may also provide us ways to fight back. The study of “cancer autoimmunity” is the other side of the autoimmune coin. “The concept here is that the immune system, which can attack and destroy cells, also has properties to attack and destroy tumors,” Rosen says.
In a healthy immune system, T cells help regulate the immune response and coordinate the attack on foreign invaders. In autoimmunity, however, the T cells are activated against the self.
Elizabeth Jaffee, M.D., who co-directs centers for pancreatic and gastrointestinal cancers at Johns Hopkins, is looking at the mechanisms that subdue or activate T cells; her work might lead to better treatments for cancer, and for autoimmune disease. “We would like to be able to control these mechanisms to figure out how to activate anticancer immune cells, as well as subdue autoimmune cells,” she explains.
Johns Hopkins is a world leader in this area, one of the most promising of autoimmune research. “People didn’t think we could harness the immune system to fight cancer,” Jaffee says. “But they’re now believers. We’re entering a different age.”
Discovering What Are—and Aren’t—Contributing Factors
One of the big questions autoimmunity researchers are asking is why certain people get autoimmune diseases and others don’t. What are the triggers? Who is most susceptible? For what reasons?
Peter Calabresi, M.D., director of the Johns Hopkins Multiple Sclerosis Center, cites research on twins suggesting that while genes are a contributing factor, they don’t necessarily predestine a person for autoimmunity. “These twins have the same genes,” he says, “yet in only 30 percent of the cases does the second twin also get MS.” (In nonidentical twins, the incidence of a second twin getting the disease is 3 percent.)
Calabresi is also seeing evidence of the precise way in which autoimmunity functions. In MS, he says, researchers have thought for the last three decades that the attack is against myelin—the fatty sheath that wraps around nerves and helps conduct impulses. But recent research at the Multiple Sclerosis Center conducted on the eyes of people who have MS suggests something different.
“Some of the autoimmune response seems to be directed against the nerve itself,” he says. “That would be a big change in our thinking about how MS works.”
The analogy, he says, is that if the body is a tree, MS has been thought of as an infection of the bark. “We’re now thinking,” he says, “that maybe the immune system is poisoning the trunk.”
Fox Sports Supports Johns Hopkins Research
Johns Hopkins Medicine has been selected as one of three charities for this year’s Fox Sports Supports program—and money raised will go directly to Johns Hopkins’ cutting-edge research on autoimmune disease.
Established in 2007, Fox Sports Supports is devoted to raising awareness, providing financial assistance and spurring volunteerism for select health-related charities.
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