The Autoimmune Epidemic: Bodies Gone Haywire in a World Out of Balance--and the Cutting-Edge Science that Promises Hope (No Series) (23 page)

Indeed, researchers increasingly believe that triggers behind today’s rising rates of autoimmune disease may be similar to those behind skyrocketing rates of childhood allergies and allergy-induced asthma. Many investigators worry that such increases are further testament to the fact that the human immune system—especially a child’s more vulnerable immune system—is becoming unable to differentiate properly between what is safe and what is foreign. Consider the rise in food-related and inhalant allergies. More than half of Americans test positive to one or more allergens, more than double the percentage who did thirty years ago. Go into any elementary school these days and the basket of inhalers and EpiPens—a device for delivering a shot of epinephrine in the event of a severe allergic response—sitting on the teacher’s desk makes this all too evident. Ditto asthma, which is often allergy induced. Twenty million Americans now suffer from asthma, and 7 million of these are children. The number of people suffering from asthma in the U.S. increased 74 percent between 1980 and 1996.

The fact that autoimmunity and allergies are rising in tandem makes complete sense, since the mechanisms behind allergies and autoimmune disease are so similar: both are the result of an inappropriate overresponse, or hypersensitivity, of the immune system to something that the body doesn’t recognize as safe. An allergic reaction to food occurs when the immune system incorrectly identifies a food protein as a threat to the body. This immune response elevates the level of a blood antibody known as IgE. When IgE levels increase and a person is exposed to the food again, the body releases histamines and other chemicals to protect the body. This results in symptoms of an allergic reaction. The similarity between an allergic response and an autoimmune response is clearest in the autoimmune disease known as celiac disease—what some term a gluten allergy—in which the body perceives gluten as a foreign invader. In order to protect the body from the foreign substance in the digestive tract, the immune system produces antibodies that mistakenly attack the lining of the gut as well, resulting in autoimmune disease. Eliminate the allergen—gluten in wheat and other grains—and the autoimmune disease subsides.

Both allergies and autoimmune disease are the result of the immune system’s efforts to hold a potentially harmful foreign substance at bay. In allergies, the immune system reacts to an external substance that would normally be harmless. With autoimmune disorders, the immune system reacts to normal tissue in the body that would normally be seen as harmless. The difference is that in the case of allergies, the trigger is a known, quantifiable external stimulus (peanut butter, eggs, pollen, dust mites, trees, grass, mold), whereas in most cases of autoimmunity (other than celiac disease) the causes can often only be ascertained (or only guessed at) after disease strikes. When the immune system is pushed to turn haywire in one area, it’s more likely to go haywire in many areas.

Some studies support the theory that rising rates of immune-system-mediated illnesses are attributable to our living in too pristine a world. For example, some studies show that adults who were around infant siblings during their first six years of life have a reduced risk of multiple sclerosis. The theory is that having younger siblings increases one’s likelihood of having had infections early in life, and a lack of contact with siblings may mean one’s immune system is understimulated during those crucial years when the immune system is being educated for the future.

One new study found that gutter rats and field mice exhibit far fewer allergies and autoimmune diseases than their superhygienic laboratory counterparts. Researchers found that the immune systems of flea-ridden wild rats are busy fighting off everything from germs to parasites, whereas the immune systems of lab rats had nothing major to occupy them. With no real dangers to fight off, lab rats were more likely to make antibodies that attacked substances like pollen, or the body’s own tissue. In other words, the lab rats’ immune systems became hypersensitive to substances that would not bother their wild counterparts. One might compare this to an old person who lives alone in an apartment and has few true concerns, and so they get upset by the least little thing, like the mailman not coming on time. By contrast, someone who is experiencing a true trauma, say the loss of a loved one, is going to see small things like the late mail as entirely inconsequential.

But blaming hygiene as the sole source of today’s autoimmune epidemic doesn’t wash with all scientists, and this basic conflict of ideas is at the heart of a growing controversy. One well-known researcher who feels the too-clean theory can’t possibly fully explain today’s rising rates of autoimmune disease is DeLisa Fairweather, PhD, a young assistant professor at the Bloomberg School of Public Health’s Department of Environmental Health Sciences Division of Toxicology and a protégé and co-author with Noel Rose of many scientific papers on viral-induced autoimmune disease.

In the doorway of her office, Fairweather apologizes for the state of disarray. “Always looking for more time to read,” she says, gesturing to a picnic-sized worktable to our left, laden with dozens of research-paper stacks, some so high they’re near to toppling. To our right hangs a large whiteboard with hundreds of Fairweather’s small jotted notations, arrows flying in varied directions stressing connections between scribbled thoughts and lists punctuated with question marks.

I ask her what she thinks about the hygiene hypothesis as the primary explanation for rising rates of autoimmunity, at a time in our evolution when we’re living in the most chemically polluted environment ever. To elucidate her answer, Fairweather, her warm blue eyes animated behind tortoiseshell glasses, lines up three eight-and-a-half by eleven sheets of paper, turns them horizontally, and lays them side by side in one thirty-three-inch stretch. As she talks she diagrams for me why, in her estimation, the too-clean theory is too flimsy to explain today’s autoimmune epidemic.

Although it is true, she agrees, that allergies, asthma, and autoimmunity may be higher in countries where there are more vaccines and fewer infections in early childhood, it is also true that immigrants from other countries who are exposed to numerous infections and few vaccines as young children develop allergies and autoimmune disease at rates similar to those of Americans soon after they immigrate to this country. Likewise, countries that adopt a Western diet and become more industrialized, but don’t have the same vaccination program as we have in the United States, tend to develop allergies and autoimmune disease at the same high rates of illness that we do. Moreover, she asserts, “The hygiene hypothesis cannot explain all the babies who are born today with allergies.”

But what diminishes the too-clean theory most in her mind is that although certain childhood illnesses have lessened due to vaccination programs against well-known childhood viruses, other childhood infections haven’t let up in the least. Most respiratory and stomach-flu bugs children get are moving-target infections scientists can’t easily develop vaccines against because they mutate so quickly that by the time a vaccine is developed to fight them, the germ has already changed its structure so significantly that the vaccine is rendered ineffective. These bugs challenge the immune systems of children with unfettered constancy, as you can witness should you enter any preschool classroom or daycare center in America. Inquire of any veteran preschool teacher of thirty years and they will tell you that kids today certainly don’t seem to be out less with colds and viruses and stomach bugs than they were decades ago. Rather, it seems whole grades of preschoolers will get hit with a stomach bug one week and another virus the next, leading to half-empty classrooms several times a year. Meanwhile, new viruses such as West Nile and the spread of such infections as Lyme disease pose additional challenges to the immune system that children a generation ago never had to face. “Not all infections have lessened,” believes Fairweather. “There has to be something bigger at play.”

As someone who has dealt with numerous autoimmune disorders since puberty, I look back over my own childhood and wonder if it could have been too clean. My three siblings and I were all a year apart, and illnesses flew through our house with such vengeance that my mother says there was once a stretch of forty days during which there was always someone vomiting or feverish. Most of the time we were pretty hearty and spent every day in the summer or on weekends mucking about in the swamp to one side of our house, the woods behind us, or swimming or sailing or waterskiing like river rats in the less-than-pristine Chesapeake Bay. We were deeply in the swill, as it were, and in our younger years carried about dead mice and birds and turtles and fish skeletons, seldom washing our hands. It was life on the bay, and we’d only return after hours of getting caked in the dirt of the great outdoors when we heard our parents blowing the foghorn to let us know it was time to traipse homeward over the fields or swamps. I cannot imagine a dirtier childhood. I also had mumps and measles both. But somehow, I ended up with numerous autoimmune diseases.

The biggest point of controversy with the hygiene hypothesis, says Fairweather, is that “it does not take into account the increase in pollution and chemicals in our environment in the past fifty years, which stimulate our immune system in a similar way that infections do. We are certainly not cleaner in a chemical sense than we used to be. In autoimmune disease, the immune response looks as if it has seen an infection. Why would the lack of disease—or a too-clean environment—produce a response in the body that looks as if it has seen an infectious agent?” We know that autogens can stimulate an autoimmune response in a similar way that infectious agents do, and we know that our exposure to autogens has skyrocketed in the last half century. If our immune systems could talk, chances are they would tell us not that they are feeling challenged too little, but that they are feeling challenged too much.

BLASTING OUR CELLS

To grasp fully how our twenty-first-century immune systems may be overtaxed by constant hits, it’s critical that we understand what occurs in that very first moment when the immune system mounts its defense against either a virus or autogen. In fighting off dangerous pathogenic hits, our bodies are equipped with two basic types of immune responses. The initial immune response, known as the innate immune response, occurs when the body first detects a foreign antigen working its way past the body’s barriers. Scientists, Fairweather says, used to assume this innate immune response was not terribly sophisticated, because it only recognizes foreign invaders in generalized groups, rather than with any detailed specificity. For example, it might recognize an infiltrating germ as belonging to a broad group of viruses, but it does not register what kind of virus it’s looking at exactly. You might imagine the innate immune response’s means of dealing with an antigen kind of like the way you deal with a garden pest you’ve just noticed on your rosebush. You might spray the bush with a generic garden spray you’ve had sitting around on a garage shelf and hope for the best; it may not be a product that’s specifically meant to conquer the exact insect that’s destroying your bush, but it will probably help nonetheless because it defends pretty well against garden pests in general.

The other kind of immune response is the adaptive immune response, which takes place long past the moment when a foreign invader first infiltrates the body. It has always been assumed that all the real defensive action took place during the adaptive immune response—when the immune system sets out to detect exactly what specific type of antigen has infiltrated the body and to mount a response that targets it for destruction. Scientists believed that it was here that the immune system made the grave mistakes that would lead to autoimmune disease. Yet in her Hopkins lab, Fairweather has been able to prove that assumption to be incorrect. The innate immune system, which no one bothered to look at very closely, is a whole lot smarter and more influential in the autoimmune process than scientists have assumed it to be. Fairweather’s most recently published papers contend that the adaptive immune response is, in fact, “completely controlled by what happens at that critical initial meeting when the innate immune system reacts for the very first time to an invader.” It’s that initial moment when, say, a virus enters your body because you put your fingers—which have just touched a doorknob just touched by someone who is sick and contagious—to your lips. The innate immune response—influenced, of course, by one’s genetic susceptibility and exposure to chemicals—sets the stage for what the adaptive immune response will then decide to do.

After painstakingly uncovering the workings of the innate immune system in mice, Fairweather has concluded that the human immune system can become so besieged by unrelenting contact with a toxic barrage of viruses, chemicals, and heavy metals that it’s practically forced to run amok. The synergistic combination of chemicals in our daily food and air coupled with common viral hits, she contends, puts our immune systems through so many drills that they are on constant high alert and simply can’t handle it. According to Fairweather, when the innate immune system meets a constant onslaught of potentially dangerous challenges, be they infectious or toxic substances, it behaves like a car whose accelerator is stuck at eighty miles an hour and whose brakes aren’t working.

To understand how the brakes fail on a cellular level in the human body requires a short course in one more group of immune cells, known as mast cells. Mast cells are part of the innate immune system’s initial response team, and they work by recognizing patterns on the surface of foreign invaders through what are called “toll-like receptors.” These toll-like receptors sit on the surface of mast cells and identify all invading antigens, announcing to the body, much like an alarm system might, “Alert! Alert! Trespasser!” In response, mast cells release cytokines to signal the immune system to attack the antigen. Infectious agents aren’t the only things that can cause mast cells to react; chemicals can as well. Should mast cells be bombarded with one questionable environmental interloper after another, they signal the immune system to hit the gas pedal over and over again, until it’s as if the engine is being gunned full throttle, 24/7. The master control switch that tells the immune system to fight with all its heart gets stuck in the on position and can’t be turned back off.