Mysterious disease that causes the body’s immune system to turn against itself

Jun 25 2004

A mysterious disease that causes the body’s immune system to turn against itself also sends a warning signal to alert doctors of the onset of its worst symptoms, University of Florida physicians have found.

To date, doctors have had no way of knowing which patients with the unpredictable autoimmune disorder lupus were likely to develop one of its most dangerous and life-threatening aspects: kidney disease, which afflicts as many as half of the 1.5 million Americans who have lupus, according to the Lupus Foundation of America.

Now doctors with the Center for Autoimmune Diseases at the UF Health Science Center have identified a protein that shows up in markedly increased levels in the urine of lupus patients with kidney disease, and have located the variant of the gene that overproduces the protein. The researchers say this will eventually enable doctors to use a simple urine test to look for the presence of the protein as an early indicator of the development of kidney disease. And in article published this month in Arthritis and Rheumatism, the scientists say the findings also could open a door to the development of preventive treatments, or less toxic treatments that could be given early in the course of the disease.

“All we can do now is quote newly diagnosed lupus patients the statistics for the chance of kidney disease,” said article co-author Dr. Hanno B. Richards, co-director of UF’s Lupus Clinic. “We can offer detailed genetic testing and assess what the likelihood of the disease might be. But with MCP1 (protein), we can screen for the levels in the urine and base our need for treatment on that.”

Richards, an assistant professor in the College of Medicine, said the study results showed kidney disease was about two to three times more likely to develop in lupus patients with certain genetic variants that produce a protein called monocyte chemoattractant protein 1, or MCP1, which acts as a traffic cop that directs immune system cells toward sites of inflammation.

The researchers also have been able to detect large amounts of MCP1 in the urine of lupus patients with kidney disease, or lupus nephritis, at levels that are highest in cases of more severe kidney inflammation.

Richards said MCP1 may provide a “window” into the kidneys and eliminate the need for invasive biopsies to confirm whether a particular treatment is working. If MCP1 levels in the urine climb, the treatment is not working; if they fall, it is, he said.

Lupus, or systemic lupus erythematosus, is an autoimmune disease that may affect the skin, kidney, heart, muscles, brain and circulatory system. The disease’s intermittent symptoms vary among patients. It is difficult to diagnosis and its cause is unknown. Black and Hispanic women of childbearing age acquire the condition more frequently than do whites, and women are 10 times more likely to have it than are men.

The study evaluated 134 participants who were patients at UF’s Center for Autoimmune Diseases, 90 percent of whom were female. Richards worked closely with UF colleagues Dr. Marco Tucci, the paper’s lead author, Dr. Mark Segal, an assistant professor in nephrology, and Dr. Westley Reeves, the division chief of rheumatology and clinical immunology.

“We found that MCP1 was markedly higher in patients with kidney disease and lupus than it was in those without,” Richards said. “And we found that the genetic subtype that allows people to secrete much more of this protein is more common in patients who have lupus nephritis compared with those lupus patients who don’t develop lupus nephritis in the course of their disease.”

Because lupus is caused by overactivity of the body’s immune system, doctors prescribe immunosuppressant drugs for kidney disease treatment, including steroids. The drugs have many adverse effects, including an increased risk for infection. Kidney disease causes water to build up in the body and can lead to swelling in the ankles, the hands or around the eyes. Because water retention is most commonly caused by heart disease, the first thing a doctor will check is the heart, sometimes delaying the diagnosis of a kidney condition. Before immunosuppressants were available, many people with lupus and kidney disease died.