The Disease Process
One NIAMS-supported study found that the disease process of lupus—including the development of certain autoantibodies and some symptoms of the disease—begin before the disease is diagnosed. Because lupus is different in different people and is characterized by autoimmunity in various systems of the body, the initial presentation can be unpredictable. Many symptoms come and go over time, often delaying diagnosis and the start of therapy.
Seeking to identify patterns among early clinical events in lupus, as well as to assess whether the presence of lupus-associated autoantibodies precedes clinical manifestations, investigators looked back at the charts of 130 lupus patients, analyzing 633 serum samples taken at different times, and noting when the criteria for a lupus diagnosis were fulfilled. To be classified as having lupus, a person needs to meet at least 4 of 11 criteria. They found that in 80 percent of the patients, at least one clinical criterion for SLE appeared before SLE was diagnosed. Eighty-four percent developed antinuclear antibodies (ANAs). Discoid rashes and seizures were the earliest observed symptoms, with a mean onset of 1.74 years and 1.70 years prior to diagnosis, respectively. Oral ulcers tended to appear only after diagnosis, making this a less useful diagnostic tool. Among SLE patients with renal disease, anti-double-stranded DNA antibodies appeared before or at the same time as American College of Rheumatology (ACR)-defined renal disorder in the majority of patients who had both the autoantibodies and the renal disorder.
Researchers are also making strides in understanding how the disease process affects different organs. One NIAMS investigator reported that a subset of antibodies to DNA can be found in the blood and the brain of lupus patients with cognitive problems. These anti-DNA antibodies bind to specific receptors (NMDA [N-methyl-D-aspartate] receptors) on nerve cells in the brain. In the culture dish, binding of these anti-DNA antibodies to nerve cells results in the death of the cells. In subsequent studies involving mice, the researchers found that these antibodies affect the nervous system only when the blood-brain barrier was broken, allowing the antibodies access to the brain. Where the blood-brain barrier was broken, antibodies bound to the neurons in a specific area of the brain that helps regulate emotion and memory. Tests for cell death in that area of the brain were positive. Behavioral tests on the mice also revealed impaired cognitive function and memory. Perhaps more important was the finding that the nerve cell binding and its damage could be prevented with a drug that inhibits the NMDA receptor. Researchers say the findings suggest that such drugs may eventually be a useful therapy for people with lupus.
Treatment
Understandably, identifying and developing better treatments for lupus—and ensuring that patients receive the best treatments—are among the primary goals of lupus research. A 2005 study of 17 adults with clinically active lupus despite treatment, found that just one injection of the cancer drug rituximab eased symptoms for up to a year or more. Several participants were able to reduce or completely stop their regular lupus medications. Rituximab works by lowering the number of B cells—white blood cells that produce antibodies—in the body. It is approved by the U.S. Food and Drug Administration (FDA) for a type of cancer called lymphoma, as well as for rheumatoid arthritis. Further research is needed to better understand its effectiveness and safety and to better determine its role in lupus treatment.
Studies from the NIH Intramural Research Program determined that treatment with immunosuppressive drugs (cyclophosphamide and prednisone) can prevent or delay kidney failure caused by nephritis, one of the most serious and life-threatening complications of lupus. Other NIH-supported research has shown that lupus patients treated with hydroxychloroquine were less likely to develop severe kidney disease, had lower disease activity, and used less steroid medication.
Other research is examining barriers that keep certain populations from complying with their prescribed medical treatment, which could contribute to worse disease outcomes, including disability and death in those populations. One NIAMS-supported study of economically disadvantaged and ethnically diverse people with rheumatoid arthritis or lupus identified the fear of side effects, including long-term damage, as a major reason people failed to take prescribed medications for their disease. Other factors identified included belief that medicines are not working, problems with the health system, such as navigating Medicaid requirements and a lack of continuity with the same doctor, and medication cost.
More information on research is available from the following resources:
- NIH Clinical Research Trials and You was designed to help people learn more about clinical trials, why they matter, and how to participate, and links to how to search for a trial or enroll in a research-matching program.
- ClinicalTrials.gov offers up-to-date information for locating federally and privately supported clinical trials.
- NIH RePORTER allows users to search NIH-funded research projects and patents resulting from NIH funding.
Hope For the Future
With research advances and a better understanding of lupus, the prognosis for people with lupus today is far brighter than it was in the past. It is possible to have lupus and remain active and involved with life, family, and work. As current research efforts unfold, there is continued hope for new treatments, improvements in quality of life, and, ultimately, a way to prevent or cure the disease. The research efforts of today may yield the answers of tomorrow, as scientists continue to unravel the mysteries of lupus.
For more information on lupus and other musculoskeletal health issues, visit www.niams.nih.gov.