Authors: Rita Baron-Faust,Jill Buyon
The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (3 page)
Autoimmune Disease—Facing Our Intimate Enemy
I had never heard the word
autoimmune
before I was told that I had antiphospholipid syndrome. And that diagnosis was scary enough. Imagine having normal checkups all of your life, then having a stroke from an illness you never even heard of. You have to learn a whole lot in a very short time to understand what’s happening to you and feel in control and not frightened.E
LAINE
, 58
Y
ou probably bought this book because you’ve been diagnosed with an autoimmune disease or you suspect you may have one. Perhaps someone in your family has an autoimmune disease, such as rheumatoid arthritis or lupus, and you’re worried about your own risk.
Maybe you’re even wondering how it is that the body can declare war on itself. Simply put, somewhere along the line, your immune cells got the wrong message. Your body dispatched the battalions of cells that normally recognize and eliminate foreign invaders such as bacteria to instead destroy healthy tissue. The attack can target any area, including the joints (causing rheumatoid arthritis), the thyroid gland (causing it to become overactive or underactive), or nerve cells (leading to multiple sclerosis).
Often it’s not a single assault; immune attacks may have several targets. If you have one autoimmune disease, you’re at risk for a second or even a third disease. The specialist treating your particular problem may not be looking for these additional diseases, so it’s important to be aware that they can occur.
Immune attacks may also come in waves, often referred to as
flares
, with lulls in between; you can have symptoms for weeks and then feel perfectly fine.
This book is designed to give you the inside story of the battle within your body. We’re focusing on what makes you special as a woman and why simply being female may put you at risk of autoimmune disease. We’ll examine those diseases that are more common in women and explore how they’re interrelated. We’ll look at treatments—some of them brand-new and generating excitement and optimism—and discuss the impact of autoimmune diseases during different stages of your life.
Most important, you’ll learn some of the key signs and symptoms of autoimmune diseases, which may help you get the right diagnosis more quickly. The absence of knowledge can lead to tragedy, such as the one endured by AARDA spokeswoman and actress Kellie Martin and her family in 1998. Martin recounts the story of her 19-year-old sister Heather, whose flulike symptoms initially led doctors to think she had a severe virus. But Heather had lupus, and by the time she was diagnosed, her kidneys had been irreparably damaged by the disease. Kellie recalls:
A few days after finishing her sophomore year at college, my sister Heather couldn’t get out of bed. She experienced severe abdominal pain and leg cramping, had numerous sores in her mouth that prevented her from eating, and had a temperature of 102. The doctor said it was the flu, or just stress from her recent final exams. So we were told to wait it out; a flu or virus just needs to run its course. “There’s nothing we can do, except give her some painkillers,” they said. Three emergency room visits and three days later, the doctor finally admitted Heather to the hospital for observation and testing. In the hospital she was examined by an internist, an infectious disease doctor, and a hematologist. After running several tests and concluding that she did indeed have an unusual virus, the doctor discharged Heather.
They discharged Heather even though she still couldn’t walk, eat, or sleep. After she was home for a few days, my mom and I took Heather to another doctor’s office, where her condition was suspected two minutes after our arrival. The doctor looked disturbed at Heather’s charts and medical history. After a brief physical exam, the doctor simply sat down and talked to Heather. He listened thoughtfully as she described exactly how she was feeling. The doctor suspected that she had an autoimmune disease called lupus.
The following day she was again admitted to the hospital because of dehydration and kidney failure, both caused by lupus.We were given the list of treatments Heather would be receiving: steroids, vitamins, and fluids. During her first week at the hospital, the blood vessels in her lungs began to burst, and her breathing became increasingly labored. The doctors, who now included a pulmonary specialist, three rheumatologists, and an oncologist (and those are just the doctors I can remember at this point), found that the lupus had affected Heather’s liver and bone marrow. Therefore, the list of treatments increased to antibiotics and chemotherapy. My family believed that once Heathers condition had a name, she would receive the treatment necessary to make her better. Unfortunately, that diagnosis came too late. She died not long afterward in 1998, at age nineteen.
Unfortunately, it’s common to encounter difficulty in getting a diagnosis of an autoimmune disease. A survey conducted by the Lupus Foundation of America found that more than half of people with lupus had symptoms for at least four years and saw three or more doctors before they were correctly diagnosed. Misdiagnosis or late diagnosis, due to being unaware and not knowing what diseases the symptoms might be a sign of, is a leading cause of death in autoimmunity. So it’s imperative that you, the patient, be informed and alert.
At the same time, physicians are becoming more and more knowledgeable about diseases such as lupus with major campaigns across the country and educational efforts directed at medical students. It’s not that a particular disease may be hard to diagnose, but rather that it requires knowledge of different signs and symptoms that don’t appear at the same time but rather occur over time.
To truly understand your disease and the others for which you may be at risk, you need to become familiar with the fundamentals of autoimmunity. So that’s where we’ll begin. Think of this chapter as Autoimmunity 101.
Our immune system has several layers. The first line of defense from outside invaders is a physical barrier—the skin and mucous membranes. Harmful organisms such as bacteria can breach this perimeter when, for example, we get a cut.
Once inside, these bacteria must face a second line of defense called the
innate immune system
, white blood cells produced by the bone marrow. If you remember the old video game Pac-Man (or in this case, Ms. Pac-Man), you’ll recall those little smiley circles that gobbled up everything in their path. The Ms. Pac-Men of the innate immune system are
neutrophils
and
macrophages
(in Latin,
macro
means “big,”
phage
means “to eat”; this cell is literally a “big eater”). Billions of neutrophils patrol the bloodstream at any given time. When neutrophils see an invader (like bacteria from that cut), they grab it, suck it in, and chew it up into little pieces that are destroyed by enzymes within the cell. They are messy eaters, though. They burp back fragments of their meal, and those “crumbs” can signal other immune cells to join the fray. Not only that, but as they chomp away, neutrophils produce chemicals that also cause inflammation that helps to heal but, if allowed to go on too long, can also hurt.
Now we come to the third (and most complicated) layer of the immune system, the one that’s mainly involved in autoimmunity. It’s called the adaptive immune system—cells in this system must be told how to do their job. All of these cells are intended to recognize what is self and what is nonself or foreign.
When a nonself entity like a bacteria or virus enters the bloodstream, the neutrophils and macrophages sound the alarm and battalions of other white blood cells (
lymphocytes
) are mobilized to search out the invader, referred to as an
antigen
.
There are several types of lymphocytes in the adaptive immune system, and each has a specific job to do: T cells help identify and eliminate antigens, and B cells produce antibodies that attach to one special antigen and help destroy it.
B cells, which develop in the bone marrow, must be activated in order to produce antibodies. First, B cells encounter antigens in the circulation. Then, after a special signal from “helper” T cells, B cells multiply and intensify their antibody response, making it more specific and lethal. In autoimmune diseases, susceptible women produce autoantibodies, antibodies that attack self. We make many different autoantibodies that can interfere with the normal function of tissues and destroy them. Some antibodies specifically react with material inside the nucleus of a cell (think of the nucleus as the yolk of an egg). These are classified as
antinuclear antibodies
, or
ANAs
. These antibodies are associated with autoimmune diseases such as
systemic lupus erythematosus (SLE)
.
1
While ANAs can be an indication you may have an autoimmune disease, they’re not diagnostic in and of themselves and can be found in up to
about 15 percent of healthy people who do not have any autoimmune diseases. Some antibodies attack the fluid of the cell surrounding the nucleus, called the
cytoplasm
(the white of the egg); these antibodies are also seen in SLE, and in
Sjögren’s syndrome.
Many other antibodies attack the surface or membrane of a cell—such as a red blood cell or platelet, or in a specific tissue such as the thyroid—causing the cell (or the target tissue) to malfunction. For example, an autoimmune assault on the thyroid gland can cause it to become overactive and produce too much thyroid hormone (
Graves’ disease
), or to become underactive and secrete too little thyroid hormone (
Hashimoto’s thyroiditis
). In
multiple sclerosis (MS),
the target is the protective coating called
myelin
that’s wrapped around nerve cells in the brain and spine, disrupting communication between nerves and causing disability. In myasthenia gravis, the immune system targets the nerves that control muscles, causing progressive damage and weakness.
It is important to keep in mind that not all autoantibodies are bad. In fact, researchers have found that there are natural or protective antibodies. These antibodies are often of a type called IgM
2
whereas IgG is the type that is most associated with autoimmune diseases.
There are three main types of T cells:
- Helper T cells (e.g., Th1 and Th2). Th1 cells are associated with cellular immunity and maximize the killing efficiency of macrophages. Th2 cells signal B-cells to produce stronger antibodies
- Natural killer (NK or cytotoxic) T cells produce molecules that destroy cells carrying antigens
- Tregs, regulatory T cells (formerly called suppressor T cells) downregulate other immune responses
- Th17 are developmentally distinct from Th1 and Th2 cells. These cells create inflammation and can cause tissue injury in autoimmune diseases, an example being multiple sclerosis.
T cells are activated when they encounter an antigen, “recognizing” it through a kind of antenna on their surface, called a
receptor
, which receives signals from molecules sitting on the surface of the antigen. Cells that signal the T cells in this process are called antigen-presenting cells (APCs).
A normal helper T cell might signal a B cell that it has found a rhinovirus (which causes the common cold); the B cell would then produce the
appropriate antibody to get rid of that virus. A
self-reactive
(also called
autoreactive
) T cell would tell the B cell to produce an antibody against the body’s own healthy tissue. An NK T cell might mistake the body’s cells for a bacterium or a virus and target it for destruction. A Treg might hamper protective immune responses. Many autoimmune diseases are
cell mediated
, meaning the T cells cause damage, not antibodies.
We encounter millions of antigens during our lifetime, and we have a vast array of T cells capable of recognizing, responding to, and remembering these antigens.
3
T cells mature in the thymus gland, where their receptors are programmed to react against foreign antigens and tolerate
self-antigens
(also called
autoantigens
); T cells with receptors that react to self-antigens are usually eliminated in the thymus. But sometimes self-reactive T cells aren’t eliminated, or, as some researchers speculate, the thymus may not properly eliminate enough self-reactive T cells. Whatever the cause, rogue T cells are able to roam at will around the body, attacking healthy tissue or sending the wrong signals to B cells. New subsets of T cells are still being discovered.
T cells send signals through messenger molecules called
cytokines
and chemokines, which can also be key players in autoimmune disease. Cytokines are proteins that can activate immune cells (including other T cells) and affect nonimmune processes, directly causing inflammation and damage. A common inflammatory cytokine in autoimmune disease is
tumor necrosis factor alpha (TNFα)
. Drugs that can slow or halt the progress of rheumatoid arthritis, Crohn’s disease, and other autoimmune diseases block the destructive effects of TNFα (see
page 10
).
Chemokines
, substances manufactured by cells and tissues, act like a magnet for other immune cells. Overproduction of chemokines attracts neutrophils and macrophages (both of whom never refuse a meal), and when these cells invade tissues, inflammation and destruction can ensue.
As we mentioned, macrophages and neutrophils (also called
phagocytes
) normally patrol the body, killing foreign cells by engulfing them and destroying them with toxic molecules. After digesting antigens, neutrophils spit out tiny bits of the antigen on their surface to alert T cells to the presence of an enemy. Neutrophils also fight off infectious agents by releasing granules of potent chemicals that destroy the invaders. In autoimmune diseases, these cells become overactive and release too many of these toxic molecules, which damage surrounding tissue and contribute to inflammation. This happens in
rheumatoid arthritis, lupus, multiple sclerosis, and other autoimmune diseases.
Another cause of inflammation in autoimmune disease is the formation of
immune complexes
, latticelike structures created when antibodies bind to antigens. These immune complexes cause activation of what’s called the
complement cascade
.
If you think of antibodies as the “guns” of the immune arsenal, complement proteins function as the “bullets.” The complement cascade can be thought of as nine different bullets that can make antibodies more effective in destroying foreign invaders. When complement is activated, there is a domino effect in which one complement protein makes another one active, and this cascade winds up calling in neutrophils and macrophages, which block blood flow in small blood vessels, destroying instead of nourishing tissues and organs.
As you can see, a lot is going on in autoimmunity, which is why treatment for autoimmune disease is not as simple as a single antibiotic pill that kills bacteria. These diseases may require multidrug therapies to affect the different processes that are causing symptoms and organ damage.
