The Autoimmune Epidemic: Bodies Gone Haywire in a World Out of Balance--and the Cutting-Edge Science that Promises Hope (No Series) (26 page)

Kerr looks thoughtful for a moment before telling me about newborn infants he works with who suffer from what is known as spinal muscular atrophy. These babies have a fatal genetic flaw and do not develop a normal nervous system—and there is no way to help them. Inevitably, they die. But what if? What if, Kerr asks, we could help reconnect motor neurons to grow axonal nerves along their neural pathways according to normal developmental cues—which are still in place in newborns—so that they could develop a normal nervous system? Live normal lives? What if he could help these infants’ mothers and fathers keep their newborn children healthy and safe and alive?

What if, he asks, we can help mothers and fathers and children who have been hit with neurological autoimmune disease lead the lives they, as families, dream of leading? What if Cody Unser could get out of her wheelchair and live her dream of being able to take that first step? “I feel that my career should be judged by whether I can deliver on this hope,” Kerr tells me, his green eyes probing and earnest. “If I can’t then I should be judged a failure.” He reflects for a moment on his recent friendship with deceased actor Christopher Reeve, who, he says, “used to call me on a regular basis to see where we were with our stem-cell study—not just for his own sake, but for those he knew would survive after him. If I can look in the mirror when I’m seventy-five and say that I saved those babies who weren’t born with developed neurological systems, or that I helped parents or children be the parents and children they dream of being, that’s it for me, I’ll die a happy man.”

Still, the day when you can go to your doctor for a stem-cell injection to regenerate damaged nerves and expect to quickly regrow your axons and myelin sheaths is years off—and there are numerous scientific and political hurdles to surmount along the way. In the meantime, scientists around the globe are researching ways to prevent the immune system from attacking itself in the first place—as well as to achieve more accurate and faster diagnosis for autoimmune diseases of every sort. One of the most dramatic breakthroughs in this research centers on trying to detect distinct blood biomarkers that will alert clinicians years before symptoms begin that a patient’s immune system is on the verge of attacking his or her own body and destroying vital bodily systems.

THE BLOOD DETECTIVES

Imagine a future in which your regular checkup includes state-of-the-art blood tests that can predict with striking accuracy whether ten years down the road you’ll develop rheumatoid arthritis, lupus, multiple sclerosis, Sjögren’s disease, Addison’s disease, or type 1 diabetes. If your lab tests do prove positive for specific patterns of antibodies that predict you have, say, an 80 percent or better chance of developing one of these autoimmune diseases, your physician quickly reassures you: worry not. With finely tuned, cutting-edge intervention she can treat you in advance of any severe symptoms of disease appearing and prevent your immune cells from ever turning on you.

It may sound farfetched—not unlike the capabilities of Dr. McCoy’s handheld tricorder scanner in the futuristic
Star Trek
TV series, which could detect
Enterprise
crew members’ hidden medical ailments in a matter of seconds. Yet in labs around the world, the ability to take blood samples and use blood biomarkers to predict autoimmune disease far in advance of a patient’s falling ill is a rapidly evolving science—and a most promising one. In scientific breakthroughs that smack of
Star Trek
special effects, scientists from top medical research institutes have begun to identify the precise autoantibodies that foretell autoimmune disease in patients’ bloodstreams as early as ten years in advance of illness, potentially paving the way for preventing these diseases from causing devastating damage in the first place.

One of the scientists voyaging into this new territory is Dr. Hal Scofield, an associate member of the Arthritis and Immunology Research Program at the Oklahoma Medical Research Foundation (OMRF). Scofield serves as a professor in the Department of Medicine as well as an adjunct associate professor in the Department of Pathology at the University of Oklahoma Health Sciences Center, where he works with Dr. John Harley, chief of OMRF’s Arthritis and Immunology Research Program. Along with Harley, Scofield is coauthor of one of the most definitive works on prediagnostic biomarkers for lupus—work that has opened up a whole new window for researchers into how early autoantibodies can portend what might be happening deep in the immune system long before a single lupus symptom rears its ugly head.

One of the inherent difficulties in detecting what type of autoantibodies people may carry in their blood before they fall ill is finding a sufficient test group. Where in the world can a researcher hope to find a group of individuals with autoimmune disease who also just happen to have had their blood taken, frozen, and safely stored away for the past twenty years—allowing researchers to examine that blood to determine whether they developed autoantibodies years prior to falling sick or not?

As it turns out, there is just such a place. About twenty years ago, in the mid 1980s, when HIV (which is not an autoimmune disease) was first rapidly on the rise in the United States, the U.S. Army decided to take blood from all military personnel, both when they enlisted and each time they were deployed overseas, and to store those samples away. No one exactly knew what they planned to do with so many blood samples, but given the AIDS crisis brewing around the globe, it just seemed like a good idea at the time. The blood samples were stored at the Department of Defense Serum Repository in Silver Spring, Maryland. By 2003 the repository possessed 30 million blood samples taken from more than 5 million U.S. Armed Forces personnel—all stashed away in large silver walk-in freezers. It was a researcher’s dream, the kind of treasure trove that no one but the army could possibly have stockpiled, given the deep pockets of the Department of Defense versus the dwindling sum doled out for the typical autoimmune-disease research grant. The repository also provided a logistical dream come true for researchers: every enlisted person’s record can easily be traced back through time—unlike most civilian records, which are usually on file with a plethora of different physicians and hospitals and often can’t ever be properly reconstructed in full.

Led by John Harley, in the late 1990s Judi James, a member of the Arthritis and Immunology division at Oklahoma Medical Research Foundation, along with Hal Scofield, began to ask themselves if, using this incredible resource, they might be able to determine whether the blood of army personnel who had ultimately acquired the autoimmune disease lupus would show the presence of any particular combination or pattern of antibodies that were not present in healthy personnel.

James and Scofield—who had both been closely mentored by Harley early in their careers at Oklahoma—had good reason to believe that this might not be a farfetched idea. In the 1980s other researchers working with infants born with a rare disease known as neonatal lupus had noted a fascinating but unsettling health pattern among these newborns’ mothers that had led them to ask a similar question.

Babies born with neonatal lupus, a disease in which the immune system attacks the tissue of one or multiple organs in the baby’s own body, have a lupuslike rash and very slow heartbeats—often as low as thirty to forty beats a minute. Sometimes they are born with heart block. Yet mothers of infants with neonatal lupus are often surprisingly quite healthy and free of lupus at the time that they give birth. Over time, however, researchers working with infants with neonatal lupus began to notice that four or five years down the road, mothers who had been seemingly healthy at the time of giving birth were routinely developing either lupus or lupus-related Sjögren’s disease, an autoimmune disease in which sufferers experience symptoms such as dry eyes, dry mouth, and difficulty swallowing. Curious as to whether this could have been predicted, scientists took blood samples from twenty-one mothers of babies with neonatal lupus—including those mothers who had no symptoms of any disease—looking for specific autoantibodies that were indicative of lupus and Sjögren’s. They discovered that these autoantibodies were present in all of the mothers who had given birth to babies with neonatal lupus. Indeed, over the next ten years, eighteen of these mothers went on to develop symptoms of lupus or Sjögren’s. Evidently, these mothers were carrying the autoantibodies indicative of lupus and Sjögren’s years before falling ill.

In 2000, the three Oklahoma researchers, along with researchers at the Walter Reed Army Medical Center, began working with stockpiled blood samples sitting at the Department of Defense Serum Repository. They set out to compare the blood work of 132 servicemen and women who were initially healthy but who later developed lupus with personnel who did not develop lupus. They were searching for a group of five different antibodies that, individually, go by names such as anti-nRNP, anti-Sm, anti-double-stranded DNA, anti-Ro, and anti-La antibodies.

Collectively known as ANA, or antinuclear antibodies, these antibodies are able to bind with the nuclei of tissue and organ cells and inflict damage. When clinicians test a patient who has lupuslike symptoms, they look for one or more in this array of autoantibodies to help in their diagnosis. While it’s no surprise that patients already suffering from lupus would test positive for one or more of these ANA, it is another thing altogether to discover that these autoantibodies can exist in someone who is feeling perfectly fine, long before he or she feels the first twinges of malaise.

And yet that is exactly what Scofield, Harley, and James found to be the case. In 2003, they published a landmark study showing that of those servicemen and women who did develop lupus, 88 percent had at least one autoantibody to lupus ten years prior to diagnosis.

Although unaffected military personnel who never developed lupus also occasionally showed abnormal immune responses, in their cases, the autoantibodies appeared in a fleeting manner; they emerged only to disappear quickly again. Among those who developed lupus, the story was quite different. Their immune systems continued to create an increasing number of different autoantibodies right up until a few months before the onset of lupus symptoms. Looking at the bloodwork of these 132 people, a pattern emerged not unlike that of a progressive drum roll announcing the full-fledged arrival of the illness itself. Typically, one or two autoantibodies appeared ten years prior to disease, more appeared two to five years prior to disease, and several more appeared like a final drum roll just a few months before the patient experienced the first symptoms of lupus.

Scofield, a fifth-generation Texan from the whistle-stop town of Lewisville who retains a slight Texan twang despite two decades in Oklahoma City, cautions that he and other lupus researchers are still a long way from being able to pinpoint a specific pattern of autoantibodies that is 100 percent predictive of a person’s developing lupus. Possessing autoantibodies that are indicative of a particular illness such as lupus doesn’t necessarily mean that you’re going to develop that disease. The most definitive thing that researchers can say at this point, believes Scofield, is this: “Those who are destined to go on to get lupus have these autoantibodies in their blood long before they get the disease, and normal people who don’t have lupus don’t have these autoantibodies very often, and so we do have the chance to go on and predict who might get disease.” But scientists don’t have all the kinks worked out quite yet.

It’s still science in the making. Scofield points out that “When two people in the waiting room in our clinic sit next to each other and realize that they have lupus, often the only thing they have in common is the name of their disease. Their symptoms are different, and the autoantibodies they test positive for may be different as well.” In short, which autoantibodies appear when and in what sequence or number varies a lot from patient to patient.

Nevertheless, says Scofield, “If we can further determine this exact pattern then the exciting part is that you can identify patients before the onset of disease.” Armed with that information, doctors will be able to counsel patients who stand at a significantly heightened risk for developing a specific autoimmune disease about what symptoms to watch out for so that they can receive earlier treatment when symptoms do begin to appear. Early intervention could go a long way toward helping patients to sidestep some of the serious risks that come with lupus, including the life-threatening complications of kidney failure and major organ damage.

Scofield, Harley, James, and their colleagues are currently working to elucidate more specific patterns to predict more definitively who will have lupus. Using the blood samples of a new, larger cohort of three hundred army personnel who developed lupus, they hope to detect the precise pattern of autoantibodies and ferret out the difference between patterns that are surefire predictors of the disease versus configurations of autoantibodies that don’t necessarily mean you’re at risk of developing lupus at all.

Similar research is going on in other diseases as well, such as rheumatoid arthritis. In a 2004 study, researchers looked at blood donors who later developed rheumatoid arthritis. About half the patients had autoantibodies for the disease an average of four and a half years before diagnosis. Patients who had the marker also ended up with a more severe form of the disease than those who did not. A Swedish study of rheumatoid arthritis published in 2003 found similar results.

Although lab researchers are working hard to elucidate biomarkers that predict disease years in advance of patients’ developing autoimmunity, the irony is that many autoimmune-disease patients still struggle to receive an accurate diagnosis even when they have been terribly ill for years. The gap between what is happening in today’s top diagnostic research labs and the diagnostic struggles that most patients experience in their doctors’ offices is vast.