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The Wayward Angel
Investigating Autoimmune Disease
by Eileen Nicol

Picture the immune system as a guardian angel. We are normally unaware of its relentless vigilance in identifying and attacking the bacteria, viruses and parasites that threaten our health. And as women, our immune systems face an additional challenge in pregnancy — not to reject that very different bit of DNA growing in the womb. It’s a darn smart angel, but given its daunting tasks, it’s not surprising that it sometimes gets confused.

What is Autoimmune Disease?

In a normal immune response, the immune system identifies a toxin and produces antibodies to destroy it. Several types of specialized white blood cells called lymphocytes are involved in this process. Among these lymphocytes, T-cells identify the antigens and instruct B-cells to produce antibodies. Autoimmunity occurs when our immune system mistakes “self” tissue for “non-self” tissue and begins producing autoantibodies, that is, antibodies against “self.” Researchers have found autoantibodies in many healthy people, and it is believed that autoimmunity is benignly present in everyone to some extent. But sometimes autoimmunity becomes pathogenic, resulting in an autoimmune disease.

Autoimmune diseases can attack the joints (rheumatoid arthritis), the skin (scleroderma), the thyroid gland (Graves’ disease and Hashimoto’s thyroiditis) and the nervous system (multiple sclerosis). They can be life threatening if not treated, as in type 1 diabetes and systemic lupus, but many of them are under- or misdiagnosed, dismissed as mere complaints of tiredness or soreness. Because of this variability, the medical profession only began to consider them as a group in the past fifty years, and there is still some debate as to whether diseases such as chronic fatigue syndrome fall into the autoimmune disease category. Most sources estimate that there are over 80 autoimmune diseases. The most common are the thyroid disorders, Hashimoto’s thyroiditis and Graves’ disease, which affect 3 percent of all adult women. Overall, about 75 percent of patients with autoimmune disease are women and, for some diseases such as Hashimoto’s thyroiditis, the ratio of women to men is as high as 10 to 1. And studies indicate that women in the Pacific Northwest are at an even higher risk, particularly for multiple sclerosis.

Genetic factors in autoimmune disease

No one knows why autoimmunity becomes pathogenic in some people, but the consensus is that both genetics and environmental triggers play a part. Autoimmune diseases are not directly inherited but they do run in families, and the faulty genes don’t always produce the same problem. One family member may have a thyroid disease, and another rheumatoid arthritis, while other family members are healthy. Human leukocyte antigens, also called HLAs, are key to the immune and autoimmune responses, and HLAs are governed by genes.

In the late 1990s Dr. J. Lee Nelson, a researcher at the Fred Hutchinson Cancer Research Center, noticed the similarities between graft-vs.-host disease in bone marrow transplants and certain autoimmune diseases. This led her to look closely at HLAs and their role in the immune response. She began investigating microchimerism, which refers to the persistence of fetal cells in the mother’s body long after the birth of the child. In Greek myth, a chimera is a she-monster with a lion’s body, a goat’s head and a serpent’s tail. “In medicine it just means having cells and DNA that’s different from the majority of your cells,” explains Dr. Nelson. She speculates that it could be the similarity between the fetal and maternal HLA that confuses the immune system.

“What happens with women that’s unique is that they have some cells persisting from their mother, and then they also get the ones from their child. We think that part of the problem with autoimmune disease like scleroderma may arise because of things across generations.” (We knew we were stuck in the middle, didn’t we?) “When something’s easily visible as foreign it’s not a problem,” Dr. Nelson continues. “It’s when it’s extremely similar but actually not identical that it can be a problem because then it’s almost like a computer virus or a Trojan horse.”

All this and hormones, too!

Many women who suffer from autoimmune diseases, notably rheumatoid arthritis and multiple sclerosis, actually get better during pregnancy, and then relapse several months after giving birth. Combined with the much higher incidence of autoimmune disease in women, this has led researchers to study the role of hormones in autoimmune disease. In lab experiments with animals, estrogen can induce autoimmunity. But researchers think that hormones like estrogen may act more like an on/off switch than a cause of autoimmune diseases. Cortisol, a natural steroid, is a stress hormone that is elevated during pregnancy. It modulates immune activity like inflammation, and synthetic corticosteroids such as prednisone are used to successfully treat lupus.

Pulling the trigger

Research indicates that there’s more to autoimmune disease than genetic susceptibility. “I’m interested in the genes that lead to autoimmunity, but we know there are multiple genes and we know that that’s not enough,” says Dr. Jane Buckner, a researcher at the Benaroya Research Institute at Virginia Mason. She directs the translational research program there, which is designed to collect and analyze all kinds of information from both healthy volunteers and people with autoimmune disease, an approach she calls “bench to bedside.” “Then we can study what’s the difference between an MS patient who has rapidly progressive disease versus the one who has mild disease or relapsing/remitting disease,” she says. In addition to blood samples, researchers collect information about where people have lived, their family members’ health, and what environmental exposures they have had. Collaborating with similar researchers all over the country, they hope to unlock the mysteries of why certain people get the diseases and others with similar genes don’t. “We’ve tried to take a more comprehensive approach to asking questions about autoimmunity so that we can address the many issues that are probably additively leading to these diseases,” explains Dr. Buckner. Teasing out these variables requires sophisticated computer programs and a huge investment in interviewing and tracking patients, but these methods could prove vital in identifying the pieces of the autoimmunity puzzle.

So why us?

Think Ballard in the rain. Certain ethnic populations have a higher incidence of autoimmune disease. According to Dr. Buckner, juvenile diabetes is more common among Scandinavian populations and there is a higher incidence of MS in people descended from Northern European countries. MS has also been correlated with living above the 45th parallel for the majority of one’s life prior to age 15, leading to speculation that vitamin D plays a role in immune response, says Dr. Buckner. Yet sunlight, which is a source of vitamin D, is also a flare trigger for some lupus patients.

Dr. John Hibbs, a naturopathic physician at Bastyr University, agrees that autoimmune diseases are multi-factorial. He specifies five components to autoimmune disease: genetic susceptibility, nutritional deficiency, xenobiotic factors (chemicals acquired and stored in the body), stress, and viruses or some other microbial influence. Not all factors must be present, but two or three can result in disease. “Vitamin D is the most obvious thing that comes to mind for the latitude relationship with autoimmune disease,” says Dr. Hibbs. “I think that the more that’s studied, the tighter that argument gets.” Like everything else about autoimmune disease, the reasons for higher incidence among us mossbacks are complex, and much remains to be learned.

Is the incidence of autoimmune disease increasing? The CDC estimates that the number of Americans suffering from lupus has skyrocketed from 239,000 to upwards of 1.4 million in the last four years. Dr. Buckner says the change could be the result of changes in the demographics of the population, a true increase in disease, or an increase in the identification of cases. But Dr. Hibbs feels certain there is an actual increase in disease. “I think it has everything to do with endemic and epidemic nutrient deficiency and environmentally acquired chemical toxicity,” he says.

Coping with autoimmune disease

“The thing I tell my patients is they’re going to get to know me, because I can’t cure them,” says Dr. Buckner, who carves out one day a week from her research responsibilities to see patients. While autoimmune diseases are rarely fatal if treated, patients require regular monitoring once they obtain a diagnosis, which is not always easy. “For about two years I went from doctor to doctor trying to find out what was wrong. One said it was maybe allergies and one thought it was in my head,” says Joyce LaPlant, a West Seattle woman who has lived with lupus for 33 years. “The hard part is you look fine, but you feel awful.”

Joyce takes prednisone, a corticosteroid, which controls the flares, but comes with some unpleasant side effects, like fluid retention and a hump on the back of her neck. Like many autoimmune disease sufferers, Joyce has more than one. “I have Sjögren’s too, which is the dry eye, dry mouth,” she says. All told, she takes eleven prescriptions every day. Still, she is grateful for the support of her family, and even for the gray skies of Seattle. “Here the weather is perfect for somebody who can’t go out in the sun a lot,” she says. “I tell myself I’m not sick, I just have a problem to work around.”

Positive thinking is equally evident when speaking with Kristen Nelson, a Poulsbo woman with rheumatoid arthritis. “The whole process kind of slows you down and makes you take perspective on what’s important — it’s good from that standpoint,” she says. Kristen was only 25 in 1983 when she was hit “pretty hard and pretty suddenly.” She went from playing basketball regularly to taking up to 22 aspirin a day. “It made my ears ring and it was pretty unpleasant and that was pretty much all they could do.” In 1999 the FDA approved the biologic drug Enbrel, and Kristen eagerly tried it. “It took about six months for it to start working for me, but it made a tremendous difference,” she says.

In his naturopathic treatments, Dr. Hibbs aims to discover what factors contribute to the disease in each particular patient. He uses supervised detoxification processes that involve super-nutrients and herbs and sweating. “I think our typical autoimmune patient who works hard — and they have to work hard to be our patient — is able to use fewer of the powerful medical treatments that are typically used and sometimes stay off them altogether,” he says.

Hope for a cure

Work with the human genome project and research inspired by the AIDS virus have yielded techniques and tools that are being brought to bear on autoimmune diseases. “The goal is to cure people,” says Dr. Buckner. “What that means is resetting the immune system so it’s kind of reeducated to tolerate itself. I think we’re getting closer to doing that.” Dr. Buckner is involved with laying the groundwork for cell-based therapy, where they would remove cells from the patient and “reeducate” them in the lab. “One of our goals is to target therapy so that we don’t suppress the entire immune system but we only suppress the bad parts.” This targeted approach would be a vast improvement on the treatments that suppress the entire immune system which, as Dr. Bucker explains, is “kind of like taking a really big hammer and hitting it, when we need a little tiny stick.” Or perhaps rather than curing the disease, we can learn enough to prevent its expression. Translational studies like the ones Dr. Buckner leads, and the CDC’s NHANES (National Health and Nutrition Examination Survey) studies — which compile information from examinations and interviews of tens of thousands of Americans over the past 40 years — may offer new insights on environmental factors and autoimmune disease, allowing us to avoid and/or mitigate their effects with nutritional therapies.

Back to our immune system angel. If you suspect yours is a little hyperactive, seek help. Your symptoms could include fatigue, soreness, inflammation, rashes, difficulty concentrating, dry eyes or mouth, weight loss, yellow skin — the list is long. The American Autoimmune Related Disease Association’s Web site (www.aarda.org) is a good place to start. Learn as much as you can and explore your treatment options, whether they be naturopathic and/or medical. “I think with autoimmune disease you need to get to see a specialist and find out what you have and what’s the best course of treatment,” advises Dr. Buckner. “Remember that even though you have an autoimmune disease, you have a whole life to live.”

Eileen Nicol is a frequent contributor to Seattle Woman.

©2007 Caliope Publishing Company