LFA Research Summaries
Check out our Access: Lupus Research page which provides you access to articles from leading medical journals.
Urine May Help Track Kidney Disease and Predict Treatment Success in People With Lupus
Lupus nephritis (LN) -- inflammation of the kidney -- can damage the kidney’s ability to remove waste from the body. Currently, the best way to diagnose kidney inflammation is with a biopsy, an invasive procedure that can sometimes have serious side effects. Researchers have been working to develop specific tests that can be done on urine samples. The results of this study showed that levels of mRNA for FOXP3 could potentially become a test that can be done on simple urine samples to help figure out what is going on in the kidney and to help predict responses to current treatments for people with lupus.
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Low Level of Vitamin D Does Not Necessarily Result in Bone Disease in People With Lupus
People with lupus are advised to avoid the sun because the ultraviolet rays can trigger rashes. Some patients experience more widespread flares after sun exposure. However, sun avoidance leads to low levels of vitamin D in the body. Low levels of vitamin D are associated with thinning of the bones, or "osteoporosis." The researchers wanted to know about possible relationships between vitamin D levels in the blood, lupus treatments, and bone mineral density (BMD), a measurement of how thick bones are. The results of this study showed that people with lupus who are treated with steroids are at increased risk of having low levels of vitamin D. Although reduced levels of vitamin D are known to be directly linked to osteoporosis, this study did not show that connection.
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Earlier Steroid Treatment In Pediatric Lupus Patients Is Related to Higher Risk of Bone Disease
Steroids are frequently used to treat moderate-to-severe lupus flares because they are highly effective and work quickly. However, steroids have many serious side effects, including potentially severe damage to joints or “osteonecrosis,” which is an interruption of the blood supply to the bone. The researchers hoped to learn whether starting steroids at a younger age is a risk factor for osteonecrosis. The results of this study suggest the possibility that steroids might contribute to a serious bone complication in some children with lupus.
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Twin Study Seeks to Unravel Genetic Clues to Lupus Development
DNA contains the blueprints for all the proteins in the body. DNA is wound up in tight coils and when a cell wants to make a protein, these coils unravel to expose the instructions for making that protein. The degree to which DNA stays tightly coiled or loosens up is influenced by whether or not chemicals called "methyl groups" are attached to specific parts of the DNA. The researchers hoped to find out if DNA methylation is different between twins when one twin has lupus and the other does not.
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Study Finds Risk Factors for Heart Disease in People With Lupus
Some people with lupus seem to be at increased risk for heart disease. It would be very helpful to know about specific factors that could help to predict this risk. The researchers hoped to learn what characteristics of lupus patients might help to predict heart disease.
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Can Blood Tests Help Us Learn about CNS Lupus (Lupus and the Brain)?
Some people with lupus can develop mild or, more rarely, severe inflammation of the brain, also called Central Nervous System lupus (CNS lupus). Very rarely, people can develop serious problems from CNS lupus such as seizures or strokes. Sometimes it is hard to know the difference between CNS lupus and problems that might be due to fatigue, depression, or migraine headaches. Therefore, it would be helpful to have blood tests that could tell the difference, so appropriate treatments could be given.
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An Early Study of a New Treatment (Tocilizumab) for Lupus
Interleukin-6 (IL-6) is a protein that helps to control inflammation in the body. Lupus patients sometimes have increased IL-6 in the blood, and some studies suggest that IL-6 might go up with lupus flares. If the activity of IL-6 could be blocked, it might help to decrease inflammation.
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Immunosuppressants Render Flu Vaccination Less Effective in People With Lupus
The immune system fights off the flu in different ways. One way is by making antibodies (immune proteins) that recognize the flu virus and attack it. Another way is by activating certain white blood cells to fight the virus; this is called "cell-mediated immunity." Since cell-mediated responses to the influenza vaccine also influence how well the vaccine will work, it is important to understand how lupus may affect the body’s cell-mediated response to the vaccine.
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A Second Flu Shot Might Be More Effective in Some People With Lupus
One of the ways that the immune system fights off the flu is by making antibodies (immune proteins) that can recognize the flu virus and attack it. The immune system can also make little chemicals called "cytokines" that signal to the white blood cells to make more of these antibodies when there is a virus in the bloodstream. The flu shot is made with dead virus that can help a patient make protecting antibodies but won’t cause the full flu infection to start up. In this way, individuals can be protected in advance before they are exposed to the flu that is "going around" in their community. Some lupus patients make fewer antibodies to the flu shot than most people, and there is some concern that medications for lupus can reduce the response to the flu shot since they can suppress the immune system in other ways. If there was a way to increase these responses, then the flu shot might be more effective for people with lupus.
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Potential New Indicators of Lupus Being Studied in Children
Since the 1970s, researchers have known that lupus patients are at risk for hardening of the arteries (“atherosclerosis”). Some of this risk may be from the increased inflammation that lupus patients have in the bloodstream over many years, but some of it is from the same reasons that hold true for everybody: especially high blood pressure, high blood glucose (sugar), or low levels of "good cholesterol."
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People Who Have Both Lupus and Antiphospholipid Syndrome Might Have Higher Risk of Thyroid Disease
The thyroid is a gland in the neck which helps the body keep order over how food and nutrients are handled and how fast people grow, gain or lose weight, how the heart beats, or how blood pressure and cholesterol levels in the blood respond to these changes. A protein called "thyroid peroxidase" helps to modify other proteins that the thyroid produces that perform all of these functions. Some people make antibodies (immune proteins) against their own thyroid peroxidase (these are called "anti-TPO"). People with anti-TPO sometimes have an underactive thyroid; this causes weight gain, fatigue, and a tendency to feel cold when other people around you do not.
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New Criteria To Be Tested For Lupus Diagnosis
The American College of Rheumatology established criteria for lupus in 1982, which were most recently revised in 1997. However, as time goes by and new research is completed, it makes sense to revisit how lupus is defined.
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Belimumab Effectively Treats Lupus Flares Over a Four-Year Period
Belimumab (also known as Benlysta™) is currently being studied in Phase III clinical trials to determine whether or not it is effective for lupus. Belimumab specifically reduces the actions of a protein called “B lymphocyte stimulator,” or BLyS. BLyS is a protein that increases the lifespan and inflammatory potential of certain immune cells called B cells, which are known to be hyperactive in lupus patients. Belimumab, which interferes with BLyS, is a human antibody. This means that it looks a lot like the antibodies that the immune system makes to fight off viruses. But in this case, belimumab targets only the protein BLyS. Because it only has one target, it is called a "monoclonal" antibody.
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Belimumab Reduces Lupus Flares in a Phase III Clinical Trial
Belimumab (also known as Benlysta™) is being studied in Phase III clinical trials to see whether it might be effective for lupus. Belimumab specifically inhibits a protein called B lymphocyte stimulator, or BLyS, which increases the survival and activity of immune cells called B cells, which are known to be hyperactive in lupus. Belimumab is a human antibody, which looks very similar to the antibodies made by the immune system to protect people from infections. Most antibodies made during infections have varying structures so they can target different parts of a virus or bacteria. Belimumab only targets BLyS, so it is called a "monoclonal" antibody. Belimumab is in a class of treatments called monoclonal antibodies in which the cleverness of the human immune system has been used as the inspiration for the way a new biologic drug is constructed.
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Genentech’s Rontalizumab Is Well-Tolerated by Lupus Patients in a Phase I Clinical Trial
New treatments for lupus have to undergo a series of clinical trials to test whether they are safe and effective before the FDA can approve them for general use in patients. This trial was the first stage of testing for rontalizumab, which is a new treatment that interferes with an inflammatory protein called "interferon-alpha." Interferon-alpha is increased in many people with lupus, so it is thought that maybe this kind of treatment might work for lupus. The first stage of testing, called Phase I, is focused mostly on testing the safety of new treatments. Phase I studies are kind of like dipping your toe in the water and typically involve small numbers of patient volunteers. If the treatment seems safe enough after Phase I, then larger studies can be done to see if the treatment would help to treat the symptoms of lupus.
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Urine Components May Indicate Severity of Lupus Nephritis
Lupus may involve inflammation of the kidney, called lupus nephritis, which can impair the kidney’s ability to remove waste from the body. Since normal kidney function is vital, lupus nephritis requires aggressive treatments. Currently, the best way to diagnose kidney inflammation is with a biopsy, which is an invasive procedure that can sometimes have serious side effects. If there were tests that could be done to help diagnose and evaluate lupus nephritis without a biopsy, this would be a major advance for patients.
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MicroRNA’s Role in Interferon’s Contribution to Inflammation
Interferons (IFNs) are proteins produced by immune cells when the immune system is activated. They send different instructions to cells depending on the needs of the immune response; this can lead to cells making certain inflammatory proteins. IFNs communicate with the cells by linking up with receptor proteins along the cell surface, the way a key fits into a lock. This action sends a signal into the cell that eventually either turns on or turns off the process we recognize as inflammation. There are a number of signals and switches along the communication pathways that control inflammation, leading to the production of interferons and the ways in which interferons communicate with inflammatory cells. A group of very small substances called micro-RNA (miRNA) are thought to help in the regulation of inflammation in several ways. One way may be by interfering in the process by which genes (the genetic blueprint for the body) are translated into actual proteins (the machinery of the body).
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The Effect of Antimalarials Over Time for People with Lupus
There is some evidence that when people with lupus get older -- into their 60s and later -- lupus disease activity may lessen, with fewer flares and milder symptoms, or even disappear. This may be because the immune system usually slows down as people age, so autoimmune disease activity could also decrease. Some studies have shown that individuals who develop lupus late in life have more moderate disease than people who develop lupus when they are young. Like other lupus patients whose lupus disease is less active, older patients may continue to take antimalarial medicine to treat or prevent flares.
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Factors That Influence Pregnancy Outcomes in Women with Lupus
Although women with lupus used to be advised to avoid getting pregnant, out of fear of complications for the mother, the baby, or both, a better understanding of the complications of lupus and improved management of lupus pregnancies have resulted in improved outcomes; today at least 85 percent of lupus pregnancies result in live births. However, doctors still advise women who have active lupus kidney disease (lupus nephritis, or LN) not to get pregnant until their disease has been inactive for at least six months.
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Improving How Signs of Lupus Nephritis Are Measured
The kidneys act as filters to remove waste materials from the blood; these waste materials are then passed out of the body in the urine. Lupus that affects the kidneys, termed lupus nephritis, or LN, can cause inflammation that damages the kidney tissue. If LN is not diagnosed early and treated aggressively, this tissue damage can affect the kidneys’ ability to filter waste. If the kidneys become too damaged to function properly, a person may need to undergo regular (two-three times per week) dialysis treatments, in which the blood is circulated through a machine that removes the waste material. Lupus nephritis can eventually lead to end stage renal disease (ESRD) and the need for a kidney transplant.
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The Thyroid-Lupus Relationship
The thyroid gland makes hormones that act on many functions in the body, from how quickly cells use energy to bone development and nerve cell growth. The thyroid’s production of hormones is regulated by TSH (thyroid-stimulating hormone), which is made in the pituitary gland.
Autoimmune thyroid disease occurs when the body makes antibodies to thyroid cells. Different antibodies to the thyroid can have different effects. Some can inhibit the thyroid cells, causing an underactive thyroid (thyroiditis); others can stimulate the thyroid cells, leading to an overactive thyroid (Graves’ disease). Many of the symptoms of autoimmune thyroid disease -- fatigue, muscle pain and weakness, specific antibodies -- are also symptoms of lupus. Several studies have suggested that thyroid disease occurs more often in people with lupus than the general population.
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Treating Lupus Nephritis: Does Ethnicity Play a Role?
Lupus is seen two to three times more often in people of African American, Hispanic/Latino, Asian, and Native American heritage than in Caucasians. Information on how medications work in these populations may one day enable physicians and researchers to tailor treatment for each individual.
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How Well Does Mycophenolate Mofetil Work as a Lupus Treatment?
Nearly all medications used to treat lupus are “off-label,” meaning they were originally developed for other illnesses or disease symptoms. Learning as much as possible about how a medication disperses in the body when it is given for other uses will help to achieve the best results. How well does mycophenolate mofetil work in a person with lupus?
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Can Mycophenolate Mofetil Help Prevent Lupus Flares?
Disease flares are a hallmark of lupus. It is often impossible to predict what triggers these flares, and corticosteroid medications are often used to suppress the overactive immune system. However, the side effects of these medications become increasingly destructive over time. Mycophenolate mofetil causes fewer side effects and may also help reduce the number of disease flares overall.
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Mycophenolate Mofetil or Cyclophosphamide for Lupus Nephritis Flares?
Lupus nephritis, caused by inflammation in the renal system, is one of the more common and potentially serious effects of systemic lupus. Medications that can quickly and effectively suppress flares of disease activity are crucial for preventing damage to the kidneys and other organs. While cyclophosphamide has long been used in this capacity, it must be administered intravenously and also has undesirable side effects. Mycophenolate mofetil, an oral medication, may offer an effective and more tolerable alternative.
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A Potential New Treatment for Severe Discoid Lupus
Discoid lupus is a form of lupus that affects the skin (cutaneous lupus). In most cases the discoid lupus rash appears on the face, neck, or scalp, though it can also show up on other areas of the skin. Severe discoid lupus may result in scarring. The treatments that are used most often for severe discoid lupus are strong immunosuppressants that may have significant side effects, especially when used over long periods of time. Efalizumab (trade name, Raptiva™) works by interfering with the function of overactive immune cells that are causing disease activity. The researchers in this study wanted to see if Raptiva could be effective in treating discoid lupus.
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Chronic Lesions Versus Active Lesions in Lupus Nephritis
For many years doctors have classified lupus nephritis (LN) by the extent of inflammation and where it occurs in the kidney. Under the original classification system developed in 1974 by the World Health Organization (WHO), there were six categories, or classes, of lupus nephritis, reflecting different ways in which inflammation could affect the kidney tissue. In 2003, changes to these WHO classifications were proposed. The researchers wanted to see if the new classifications could be used to predict how LN would progress and whether it would respond to treatment.
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Antiphospholipid Antibodies: It May Matter Which Ones You Have
One-third of people with lupus test positive for antiphospholipid antibodies (aPLs). The aPLs are a group of antibodies that interact with proteins that regulate blood clotting and blood vessel stability. Antiphospholipid antibodies can interfere with the normal function of blood vessels in various ways, which in turn can lead to complications such as immediate blood clots in arteries or veins, miscarriages, or more long-term damage to blood vessels, including hardening of the arteries (atherosclerosis) and later onset of heart disease and strokes.
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Research Summaries from 2008
Predicting Preeclampsia
Preeclampsia is a condition that may occur during pregnancy, with a four-fold increased risk in lupus patients. It is characterized by high blood pressure and large losses of protein in the urine. This is dangerous for both the mother and the baby. There is no good way to stop preeclampsia other than delivering the baby as soon as possible, and no guaranteed way to prevent it, so women at high risk have to be monitored closely in the last trimester of pregnancy. Risk factors for preeclampsia include prior kidney disease and chronic hypertension.
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Olés for Omega-3s
Omega-3 polyunsaturated oils found in fish have been proven to help lower risk for heart disease. This could be relevant to lupus since there is a known increased risk for heart disease in people with lupus.
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Improving Outcomes of Lupus Pregnancies
Although most women with lupus will have successful pregnancies, serious complications can occur in some cases, perhaps none more devastating than the loss of the baby. In fact, some women with lupus have consecutive miscarriages, a condition known as recurrent spontaneous abortion (RSA).
Immunglobulins (Ig) are antibody proteins that circulate in the blood. Intravenous immunoglobulin infusion (IVIg) is a medical treatment in which immunoglobulin is administered intravenously. It has been approved as a treatment for several autoimmune diseases, and has been used as a treatment for lupus, as well as for high-risk pregnancies.
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Assessing the risk factors for heart disease
Coronary artery disease (CAD) is a serious condition characterized by the buildup of fatty deposits called plaque along the inside walls of arteries that supply blood to the heart. This build-up of plaque is known as atherosclerosis, and is commonly referred to as "hardening of the arteries." People with lupus may have additional risks for developing premature atherosclerosis, either from inflammation in the blood vessels or as a side effect of some of the medications they may take.
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Lupus as a risk factor for heart disease
People with lupus have risks for coronary heart disease (CHD), in part because they exhibit some of the "traditional" risk factors that other patients share and also possibly as a result of lupus disease activity and the medications used to treat it. These risks may sometimes be hard to separate out, since lupus inflammation and/or treatments may have direct or indirect effects on traditional risk factors.
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Vitamin D deficiency and heart disease
Vitamin D is an essential element that promotes bone growth, contributes to the immune system, and plays a role in a number of other cellular functions. Low levels of vitamin D have been associated with osteoporosis, type 2 diabetes, autoimmune diseases, and cardiovascular disease -- and it is estimated that one-third to one-half of all otherwise healthy middle-aged or elderly people have a vitamin D deficiency.
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Detecting damage to arterial walls
People with lupus have an increased risk for developing atherosclerosis, commonly referred to as "hardening of the arteries." As the disease progresses, the walls of the arteries -- called the intima media -- thicken, and the passage through which the blood flows narrows as fatty plaque deposits build up along the walls of the arteries.
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Is Hormone Replacement Therapy During Menopause Safe for Women with Lupus?
Data from two very large studies -- the HERS trial (for Heart and Estrogen/Progestin Replacement Study) and the Women’s Health Initiative -- have raised questions about the use of hormone replacement therapy (HRT) for women during menopause; those studies seemed to show that HRT increases a woman’s risk for heart disease. This is of even greater concern for women with lupus, because lupus puts women at higher risk for heart disease.
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New Ways to Detect Lupus Nephritis?
Kidney disease is diagnosed through a series of laboratory tests, and usually confirmed through biopsy. Biopsy -- in which kidney tissue is removed via insertion of a needle through the person’s back and then examined under a microscope -- is the most accurate way to discover the amount of damage that has occurred from lupus disease activity. However this procedure, which typically takes place in a hospital, can be expensive, can have side effects, and would only be done after kidney disease is suspected. For these reasons, less invasive and less expensive ways to routinely measure inflammation in the kidneys and disease progression would be of great benefit.
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More Promising News About Tacrolimus
Tacrolimus is an immunosuppressant drug that helps control inflammation. It was originally developed and approved to help prevent rejection of the new organ in transplant patients, but in recent years tacrolimus has been used to treat adults with lupus or rheumatoid arthritis. The researchers wanted to know if tacrolimus could be used safely to control lupus nephritis in pediatric-onset lupus patients with long-standing disease.
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Are Increased Levels of Nitric Oxide a Sign of Kidney Damage in Lupus?
Lupus disease activity often occurs without any apparent signs or symptoms. This is especially true when lupus affects the kidneys, which is known as lupus nephritis. It is even possible for lupus to cause significant kidney damage even before a patient is diagnosed. Though there may be no visible symptoms, there are chemical changes occurring in the cells and tissues that can be measured. Therefore, a major emphasis among lupus researchers is to find ways to tell if simple laboratory tests can be used to detect otherwise silent lupus disease activity. A laboratory test that can be used in this way is called a biomarker. One potential biomarker that is being investigated is nitric oxide (chemical symbol, NO), since it is one of the chemicals involved in the body’s immune response.
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A Clue to Congenital Heart Block
Neonatal lupus is a condition that can occur when anti-SSA/Ro antibodies cross the placenta in pregnancy from the mother to her developing baby. Babies born to women who are positive for anti-SSA/Ro antibodies (even those who do not have lupus) are at greater risk for neonatal lupus, although this remains rare. A number of symptoms are seen in infants who are born with neonatal lupus, most commonly skin rashes or liver involvement, which go away over time as the infant’s own immune system develops, and the mothers antibodies are cleared from the baby’s system. Even more rarely, however, there is a potentially life-threatening heart condition that these babies can be born with, called congenital heart block (CHB).
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Why Certain Patients Don’t Respond to Steroids: One Possible Explanation
Steroid medications are often prescribed for people with lupus or other autoimmune diseases such as rheumatoid arthritis. Although they have many undesirable side effects, steroids work quickly and very well to control lupus. However, for a small percentage of lupus patients, steroids don’t provide relief; these patients are said to be "steroid resistant" (SR), and must take other medicines, most of which do not respond as rapidly to treat their disease flares.
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