Searching the Genetic Code for Clues to Lupus

As with many human autoimmune diseases, the root cause of lupus has eluded researchers.

"Although we don't know exactly what causes lupus, we do know there's a genetic predisposition and some environmental triggers," says rheumatologist Mary E. Cronin, MD, Medical College of Wisconsin Associate Professor of Medicine.

Possible triggers include hormones, certain medications, viral infections, sunlight exposure, stress, and vitamin D deficiency.

According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), "In lupus, the immune system produces antibodies against the body's healthy cells and tissues. These antibodies, called autoantibodies, contribute to the inflammation of various parts of the body and can cause damage to organs and tissues." Inflammation occurs in many autoimmune disorders.

Multiple Organ Involvement
Lupus can affect organs including the heart, lungs and kidneys, the joints, and the central nervous system. The course of the disease can vary from mild to severe, and no two patients have the same symptoms. Lupus is characterized by periods of illness, called flares, and periods of wellness, called remissions.

Dr. Cronin, who sees patients with lupus, rheumatoid arthritis and other rheumatological and muscle diseases at the Froedtert & Medical College Rheumatology Clinic, explains that even mild illnesses can turn into big problems for people who have lupus.

"Perhaps you're predisposed to lupus and you get a viral infection," she says. "Suddenly, it triggers your immune system to overreact in many ways. You develop antibodies to multiple antigens, or proteins, throughout the body. Some of these result in kidney disease and some cause inflammation in the brain or other areas of the body. Once that process starts, it's self-perpetuating unless we stop it."

Although lupus does tend to run in families, she adds, "for most patients with lupus, it's sporadic, and they have no family members with the disease. We do know that all the autoimmune diseases seem to go hand in hand, and certain genes can be overrepresented in patients with lupus. But with the majority of lupus patients, we have no idea which genes are associated with their disease."

She notes, however, that among identical twins, if one twin has lupus, the chances that the other will develop it range from 25% to 50%. With fraternal twins, both twins will develop lupus in only about 5% of cases, which is about the same ratio found among siblings who are not twins.

Role of Hormones
Because many more women than men develop lupus, it seems likely that female hormones play a key role in the disease process. "The fact that the peak age for lupus is from 15 through 40 - the childbearing years - indicates a hormonal role," Dr. Cronin says. However, she adds, children and even newborns can develop lupus, and so can older people. Among older and very young patients, however, the gender ratio falls dramatically from 9 female to 1 male in the 15 to 40 age group, to 2 female to 1 male among younger and older patients.

"The disease is can be quite different among the very young and the older populations, compared with women of childbearing age," she says. "Pediatric lupus is more likely to affect the kidneys and can be quite severe. In older patients, symptoms might include inflammation around the lungs, arthritis, and fevers."

Not long ago, Dr. Cronin notes, women with lupus were advised against becoming pregnant. "They are at higher risk of flares with pregnancy. Today, we don't tell people not to become pregnant, but we watch them carefully. We'd like them to be in remission for at least six months before they consider becoming pregnant." Most patients continue taking at least some of their lupus medications during pregnancy, she adds.

Lifespan Increases
Years ago, lupus patients typically didn't live as long as other people, but today, improved treatments help them live normal life spans. They do, however, have a 10% higher risk of heart attack than the overall population, so they are carefully monitored to prevent elevated blood pressure and cholesterol levels.

Meantime, researchers continue to search for clues that point to what triggers lupus, and considerable time and money are being spent on efforts to crack the genetic code to determine which genes are involved when the disease develops.

The actual number of patients with lupus is hard to determine, Dr. Cronin says. Because its symptoms can mimic those of other many other conditions, "it's a good idea to see a rheumatologist" who has a variety of tests to help diagnose this puzzling disease.

"There is no perfect medication right now for lupus," Dr. Cronin says, "but there are lots of studies involving innovative new treatment approaches, and we're using many of them in clinical studies here. Diagnosis and treatment are much better today than a few years ago, and these factors contribute to improved lives and longer life spans. I'm very optimistic for the future."

Barbara Abel
HealthLink Contributing Writer

For more information on this topic, see the HealthLink article Autoimmune Disorders: When the Body Attacks.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.