Scientists find genetic variants that increase lupus risk
Scientists have pinpointed a set of common variations in human DNA that signal a higher risk for lupus in women who carry them. Some of these variations are more common in relatives of lupus patients, which may help future studies examining whether lupus is more prevalent among certain racial and ethnic groups, according to recent lupus news.
In a new study – the largest of its kind to date – the International Consortium for Systemic Lupus Erythematosus (SLEGEN) looked at the genomes of 6,728 people. They found several variations, which they believe may be linked to as many as 67 percent of all lupus cases in women, located on various chromosomes in women of European ancestry. The variants helped to identify those who had up to twice the risk of getting lupus compared to those who did not have the variants.
The findings point to various drug targets important to the search for cutting-edge lupus treatments, according to the study’s authors. In addition, the study will help in the understanding of the causes of lupus and in the development of new genetic tests to find those most at risk for the disease,” says Jeffrey Edberg, PhD, an associate professor of medicine in the UAB Division of Clinical Immunology and Rheumatology and co-author on the study.
Using the data from the study, the researchers are developing further studies to determine if the same gene variants signal higher lupus risks in certain ethnic or racial groups. Also, the scientists are examining how these genetic pathways contribute to developing lupus.
This new finding, published in the January 20 online issue of Nature Genetics, is one of three published by SLEGEN in the current issue of the journal underscoring the importance of genetic variants in diseases that affect immune function. Two other studies of lupus genetics were published in the New England Journal of Medicine and the journal Immunity. All of these new studies come just weeks after the identification of a gene called TNFSF4, one of the first genetic risk factors for lupus.
New approach for attacking lupus identified
Investigators at Hospital for Special Surgery have identified two new targets for drugs aimed at controlling lupus. If companies are able to develop drugs that home in on these targets, say the investigators, patients may be able to control their disease with few side effects.
The targets are two kinase enzymes in the calcium signaling pathway, CAMK and Pyk2, which the researchers have found could be manipulated to control a protein called STAT1. STAT1 mediates the autoimmune and inflammatory functions of a chemical called interferon that has been found in abnormally high levels in people with lupus.
While drugs exist to block interferon, blocking the chemical inhibits its wanted effects – protecting the body from viruses – along with its unwanted effects. Thus, giving a patient these drugs could leave them vulnerable to illnesses and infections, some of which could be deadly.
Blocking STAT1, however, could inhibit inflammation and autoimmunity without interfering with interferon’s ability to protect against infection, say the researchers. “Our idea is that if you block these calcium pathways, you could block the deleterious effects of the interferon, but maintain the antiviral effects,” says Lionel Ivashkiv, MD, director of Basic Research at Hospital for Special Surgery in New York City, who led the study.
This lupus news was published online this week in Nature Immunology and will appear in print in February.
Compounds may help doctors detect lupus kidney disease
New research funded by the Arthritis Foundation suggests that high urinary levels of four compounds may one day help doctors detect and possibly treat lupus nephritis, a potentially deadly kidney disease associated with lupus.
In studies of laboratory mice with lupus nephritis, researchers at the University of Texas Southwestern Medical Center found that the urine of the mice had elevated levels of the four compounds – VCAM-1, P-selection, TNFR-1 and CXCL 16 – particularly at the peak of their lupus-associated kidney disease. Further study showed that people with lupus nephritis had elevated levels of the same four compounds.
The researchers believe that testing the urine for the compounds could be a way to detect the nephritis early, so that kidney-sparing treatment may be initiated. Furthermore, they suspect that one or more of the compounds might be targets for potential drug therapies for the disease. The research is published online at the Journal of Immunology.
CellCept linked to pregnancy loss and birth defects
Mycophenolate mofetil (CellCept), a drug that suppresses the immune system, has been linked to an increased risk of first-trimester pregnancy loss, the FDA warned health-care professionals this week.
The warning, which was based on post-marketing data from the U.S. National Transplantation Pregnancy Registry and Roche worldwide adverse reporting system, also revealed an increased risk for congenital malformations.
CellCept is approved for use in organ transplant patients for preventing rejection of transplanted kidneys, hearts and livers. It is also used in the treatment of lupus to suppress the abnormal immune response in the disease.
Women of childbearing potential who must take CellCept should use two methods of contraception beginning four weeks before starting treatment and should have a negative pregnancy test during the week before the first dose. They should continue to use contraceptives for six weeks after they stop the drug. Because CellCept affects hormone levels, it could potentially reduce the effectiveness of oral contraceptives.
Vaccine-like treatment shows promise against lupus
Researchers at Perdue University have developed a vaccine-like treatment that shows promise for controlling lupus without the sometimes devastating side effects of current lupus treatments. In a study published in the September-October issue of Molecular Pharmaceutics, the treatment not only improved lupus symptoms but also extended the lives of laboratory mice with a disease comparable to human lupus.
The treatment, called folate-hapten-targeted immunotherapy, targets abnormal immune cells in a way that marks them for destruction by the body’s immune system without affecting healthy calls. The researchers say their study suggests the new therapy warrants further evaluation as a possible approach for treatment of lupus in people.
Researchers may have found a new form of lupus
New research published in the Journal of Experimental Medicine suggests there may be more than one type of lupus, explaining why some people with the disease don’t respond to therapies that target its suspected mechanism.
Current thinking about lupus is that it is a disease driven largely by cooperation between B cells and T cells, two types of cells that normally help fight infection or cancer, say the study’s authors. The new research suggests that, for at least some people, rogue B cells alone may responsible for the disease.
Research has shown recently that as many as a quarter of lupus patients have high blood levels of a molecule called BAFF, which is normally needed for B cells to mature and survive. In the new study, Australian researchers found that mice with high levels of BAFF, but without the capacity to develop T cells, develop a disease that is indistinguishable from the disease requiring collaboration of both types of cells.
While the research is preliminary, this lupus news suggests that for some people, new therapies to target rogue B cells – not the T-cell/B-cell collaboration – may be the most effective treatment for lupus.
Transplant drug may be useful for treating lupus
A drug similar to one used to prevent organ-transplant rejection in people attacks a key biochemical process in the faulty immune cells of mice prone to lupus, new research shows.
The drug, an analog of rapamycin (Sirolimus), was found to shut down specific biochemical processes in the B-cells of the mice. In human lupus, B cells produce abnormal antibodies that attack the person’s own tissues.
The drug was very effective in improving all aspects of the disease in lupus-prone mice, says Chandra Mohan, MD, PhD, professor of internal medicine at the University of Texas Southwestern Medical Center and author of the study appearing in the August issue of the Journal of Clinical Investigation. The next step will be to see if the same biochemical pathways exist in humans. If they do, this research and treatment could prove very significant, he says.
