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Autoimmune Disease and RAUnderstanding the role played by the body’s immune system in the progress of rheumatoid arthritis. By
Annie Stuart Reviewed by Louise Chang, MD What do rheumatoid arthritis (RA), type 1 diabetes, Graves' disease, and multiple sclerosis have in common? One affects joints, another blood sugar. One puts the thyroid into “overdrive.” And the last condition affects the brain and spinal cord. Although the diseases seem pretty different, there is one common denominator. They are all believed to be autoimmune diseases. RA is one of about 80 different types of autoimmune diseases. After cancer and heart disease, autoimmune diseases are the most common type of disease in the U.S., affecting 50 million Americans. Women make up nearly eight out of every 10 people with an autoimmune disease. What is the common link between autoimmune diseases? And how does autoimmunity lead to rheumatoid arthritis? Here’s what you need to know. What Is the Immune System?To understand autoimmune diseases such as RA, it helps to know how the immune system normally works. Its most important job is protecting your body against foreign “invaders,” such as bacteria and viruses. White blood cells are the agents of the immune system. The immune system works in two main ways. It either directly attacks foreign invaders or it produces proteins called antibodies that attack the intruders. “Normally, the choreography of this interaction between the white blood cells works very well,” says John A. Peyman, PhD, program officer in the clinical immunology branch of the National Institute of Allergy and Infectious Diseases (NIAID). He tells us that the body can tell what is a threat and what isn’t. When you have a cut on your finger, for example, you may end up with a small infection caused by germs that enter the wound. This prompts a type of immune response known as inflammation -- often marked by redness, swelling, heat, and pain. Then the immune system’s white blood cells heal the wound and remove the infection. What Are Autoimmune Diseases?With an autoimmune disease like RA, however, something goes awry. The white blood cells overreact to stimuli inside the body. Instead of protecting the body from infection or disease as it normally does, the immune system attacks and destroys the body’s healthy tissue. It does this by producing antibodies against the body’s tissue. This is called autoimmunity. When the disease affects many organs, as in lupus, it’s called a systemic autoimmune disease. If it affects a single organ or type of tissue, such as in type 1 diabetes, it’s known as a localized autoimmune disease. Different autoimmune diseases often cluster in families and may affect almost any organ in the body. When they do, they may cause abnormal growth or changes in function. There are some similarities to allergies in the way the body reacts negatively with an autoimmune disease. The difference is that with allergies, the body’s overreaction and response is to external factors such as dust or dander. With an autoimmune disease, the body is responding to itself. Virginia T. Ladd, RT, is president and executive director of the American Autoimmune Related Diseases Association Inc. (AARDA). She tells us it helps to think of autoimmune diseases the way we think of cancer. In other words, it helps to think of them as a disease category. “There are more than 100 different forms of cancer,” Ladd says, “but they’re all formed by a mutant cell that the immune system allows to proliferate.” She says that autoimmune diseases also share a common disease pathway. “They’re all caused by the immune system attacking its own tissue.” For this reason, she says, we need a shift in our thinking about autoimmune diseases. In the past, these diseases have been looked at as individual “cars on a train” with too little focus on the “engine” that’s driving the train. In her view, research into autoimmunity has been stymied by specialization of medicine, which is organized by the organ - not the origin - of disease. This is especially important because autoimmune diseases often run in families. And members of these families often develop different types of autoimmune diseases. “If you were going in to see a doctor for joint problems, would you think it mattered to mention that your brother had Crohn’s?” Ladd asks. Probably not. Most people wouldn’t put two and two together. Understanding this connection is very important, though, because early diagnosis and treatment of an autoimmune disease like RA can often make a big difference. What Causes Autoimmune Diseases?The causes of autoimmune diseases remain unknown. Much more research is needed to fully understand them. However, evidence is pointing to infectious agents, such as viruses and bacteria. They may be important triggers in people who have a certain genetic makeup. Smoking or drugs also may trigger these chronic diseases. “The initiating cause can occur up to four years before any clinical symptoms appear,” Peyman says. “Everyone should be aware that they can reduce their risk of developing these diseases,” Peyman says. “As with cardiovascular disease and many cancers, inflammation is a major factor in the dysfunction of the immune system with autoimmune diseases. A diet rich in antioxidants and smoking cessation are good places to begin in reducing inflammation, he says. What Is Rheumatoid Arthritis?Joint destruction is the hallmark of RA. The immune system attacks joint tissues for unknown reasons. By placing magnet spots will help the swelling and inflammation. White blood cells travel to the joint lining, or synovium, and cause inflammation known as synovitis. This leads to symptoms of warmth, redness, swelling, and pain. The chronic inflammation of RA causes the normally thin synovium to become thick and joints to become swollen and puffy. With time, the inflamed synovium invades and destroys the cartilage and bone within the joint. Researchers studying rheumatoid arthritis now believe that it begins to damage bones during the first year or two that a person has the disease. That’s one reason why early diagnosis and treatment are so important. About 1.3 million adults have RA. That’s down from a 1990 estimate of 2.1 million. The decrease partly reflects a more narrow definition of RA. However, the prevalence of RA does appear to be declining around the world. Women with rheumatoid arthritis still outnumber men two to one. What Causes Rheumatoid Arthritis?Recent research is uncovering a complex interplay between the hormonal, nervous, and immune systems in rheumatoid arthritis. Researchers are also trying to learn why rheumatoid arthritis often improves during pregnancy. One study suggests that certain proteins passed between the mother and unborn child may be responsible for the improvement. These are proteins that help the immune system tell the difference between the body’s own cells and foreign ones. This exchange of proteins may change the mother’s immune system during pregnancy in some way. Both genetics and environmental factors combined appear to be the main triggers of RA. Genetics. Those at risk for autoimmune diseases such as rheumatoid arthritis inherit certain types of human leukocyte antigens (HLAs). These are white blood cell proteins that cause the white blood cells to overreact. This genetic difference puts related family members at an increased risk for one or more autoimmune diseases. Researchers are collecting information from families to gain even greater insights into genetic links. They have identified several genetic regions that increase the susceptibility for rheumatoid arthritis in animal models. Recent studies have found several novel genes associated with the disease. Environmental factors. An original insult from an infection or other factor in the environment can lead to chronic arthritis years later. This makes it more difficult to identify the culprit. However, researchers are homing in on some possible targets, Peyman tells us. They include:
“Recent studies show that smoking tobacco modifies proteins in the lungs,” says Peyman. “These modified proteins are similar to those showing up in inflamed joints.” Cells travel from the lungs to an injured joint, where the immune system reacts strongly, causing ongoing inflammation.” A similar process can happen with an infection. In people with genetic susceptibility, a minor localized infection in the mouth, for example, can trick the immune system into looking other places for modified proteins. This can lead to a “smoldering additional inflammation” in the body, which chronically attacks the joints, Peyman says. “This molecular mimicry is the basis of much of the research into the immunology of autoimmune disease,” Peyman says. “Researchers are trying to find which components of a microbe or environmental insult are similar to the known targets of the immune system in autoimmune diseases. With rheumatoid arthritis, this has been a decades-long quest.”
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