Lupus is the focus of intense research as scientists try to determine what causes the disease and how it can best be treated. Some of the questions they are working to answer include: Why are women more likely than men to have the disease? Why are there more cases of lupus in some racial and ethnic groups, and why are cases in these groups often more severe? What goes wrong in the immune system and why? How can we correct the way the immune system functions once something goes wrong? What treatment approaches will work best to lessen lupus symptoms? How do we cure lupus?
To help answer these questions, scientists are developing new and better ways to study the disease. They are doing laboratory studies that compare various aspects of the immune systems of people with lupus with those of other people both with and without lupus. They also use mice with disorders resembling lupus to better understand the abnormalities of the immune system that occur in lupus and to identify possible new therapies.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has a major focus on lupus research in its on-campus program in Bethesda, Maryland. By evaluating patients with lupus and their relatives, researchers at the National Institutes of Health (NIH) are learning more about how lupus develops and changes over time.
The NIAMS also funds many lupus researchers across the United States. To help scientists gain new knowledge, the NIAMS sponsored the development of a Lupus Registry and Repository that gathers medical information, as well as blood and tissue samples from patients and their relatives. This gives researchers across the country access to information and materials they can use to help identify genes that determine susceptibility to the disease.
The NIAMS also helped establish a registry to collect information and blood samples from children affected by neonatal lupus and their mothers. Information from the registry forms the basis of family counseling and tracks important data such as recurrence rates in subsequent pregnancies. The hope is that the registry will facilitate improved methods of diagnosis, as well as prevention and treatment for this rare condition.
In 2003, the NIH established the Lupus Federal Working Group (LFWG), a collaboration of the NIH Institutes, other Federal agencies, voluntary and professional organizations, and industries with an interest in lupus. The Working Group is led by the NIAMS and includes representatives from all relevant U.S. Department of Health and Human Services (HHS) agencies and other Federal departments having an interest in lupus.
In 2014, the NIH, pharmaceutical companies, and nonprofit organizations together created the NIH Accelerating Medicines Partnership (AMP). The goal of the AMP is to increase the number of new diagnostics and therapies for select diseases, including lupus, and to reduce the time and cost of developing them. Here are some recent major advances in different areas of lupus research:
Genetics
Identifying genes that play a role in the development of lupus or lupus severity is an active area of research.
The NIAMS intramural and extramural investigators have established that a variant in a gene called STAT4, which is associated with lupus susceptibility, is more specifically associated with disease characterized by severe symptoms such as disorders of the kidney. This finding may allow doctors to determine which patients are at risk of more severe disease and may lead to the development of new treatment for patients at greatest risk of complications.
A number of other genes associated with lupus risk and severity have been discovered. Some are linked to patient populations at high risk for lupus, including African American and Hispanic individuals.
Biomarkers
Biomarkers are another significant area of lupus research. Biomarkers are defined as molecules that reflect a specific biological or pathological process, consequence of a process, or a response to a therapeutic intervention. Simply put, they can let the doctor know what is happening in the body—or predict what is going to happen—based on something reliably measurable in tissues, cells, or fluids. NIAMS-supported researchers identified anti-double-stranded DNA antibodies and complement C3a—both of which can be found in blood tests—as biomarkers for flares, meaning they can predict that a flare will occur. They also showed that moderate doses of prednisone can prevent flares in people having these biomarkers.
In separate research, NIAMS-supported investigators identified a list of proteins in the urine of people with renal disease caused by lupus. These biomarkers can be used to indicate the type and severity of renal disease in these patients, as well as the extent of damage to the kidney. Such biomarkers could form the basis of clinical tests to help doctors establish an effective treatment plan for these patients without putting them through repeated kidney biopsies. Further studies are needed to determine whether urine protein analysis could replace the use of biopsies to assess kidney damage in lupus.
Other recently identified biomarkers include C-reactive protein (CRP), a protein made by the liver, which correlates with disease activity and cardiovascular disease risk factors, and C4d, a protein in the blood that may indicate lupus disease activity or kidney involvement.
For more information on lupus and other musculoskeletal health issues, visit www.niams.nih.gov. Join us next month for part 8 of the series on lupus.